Behaviors and Mental Disorders

All Conditions

Neoplasms

Symptoms and General Pathology

Nervous System Diseases

Depression

Neoplasm Metastasis

Back Pain

Low Back Pain

Depressive Disorder

Pain

Neurologic Manifestations

The assigned participants will receive an intervention based on gamification and the use of behavior change techniques to reduce sedentary lifestyle. Thus, a new mobile application will be used for 12 weeks that proposes to the user the realization of activities with the aim of reducing their sedentary behavior. The development of the application is based on previous analyzes that propose 6 clusters that encompass 33 factors that influence sedentary behavior. In this way, the application is designed to act on the two accessible: social support and behavior. On the social support, he proposes to the user to share his achievements in social networks or in an internal network of game users. In terms of habit modification, behavior modification strategies proposed in the Michie et al. (2013) taxonomy are applied, such as the following: establishment of personalized goals, rewards and reminders, awareness of achievements achieved, among others

The control group will receive the usual indications about the harms of sedentary lifestyle and the benefits of physical activity, not receiving specific intervention. In case the use of the intervention applied in the experimental group is beneficial, the participants assigned to the control group will be offered the opportunity to receive the intervention outside the study to allow the benefit to be used.

The information group will receive through a mobile application tips to reduce sedentary lifestyle and promote healthy living habits.

Digital intervention

The objective of the project is to analyze the clinical effectiveness of a gamifield mHealth application (iGAME) and developed in the context of lifestyle modification, but with the approach of the Behaviour Change Technique, through a randomized clinical trial that affects secondary prevention in three clinical subtypes of noncommunicable diseases, where lifestyle modification is the center of its best practice.

Despite digital exposure, gamification of health has been widely understood and often applied ad hoc in health products. Attempts to incorporate game concepts into digital health applications have not led to demonstrated success. Recent studies have shown that only 4% of the best rated health apps in Apple stores and Google Play (based on revenue and download) have gamification elements, but less than 5% of these health apps have been included in the application library of National Health Service. In addition, very little of 5% was developed for industry and health professionals.

If the power of digital technologies, such as games for clear clinical benefits, is not released, opportunities for social and economic burial will be lost for all stakeholders in the digital health and digital economy ecosystem.

A number of factors in this barrier:

* The best techniques for the design of activities. The majority of health gamification has little consistent support of health or clinical theories.
* The high cost and complexity of the digital game development process. The majority of gaming functions are based on best practices in the development of digital games.
* Little participation of researchers in health, professionals and participation of the end user in the process of gamification development. Very little health gamification is formally evaluated clinically.

The initial hypothesis is that after 12 weeks of participation in the original iGAME application, participants will increase the quantity and distribution of energy consumption, through the estimation of results, data based on acceleration and questionnaires. automatic information In addition, it will also improve satisfaction and lifestyle, as well as the consumption of health services.

Two groups study. One group with intervention (app mobile program); second group as control. At the end of the intervention, the control group receives advice of demonstrated effectiveness in the intervention to comply with the ethical principles.

The system of randomization for the participants is through an external computer system.

Digital Intervention for the Modification of Lifestyles (iGame)

Effectiveness of a Digital Intervention Based on Modification of Lifestyles in Secondary Prevention: iGAME Controlled Randomized Clinical Trial

The results emerging from this study are positive, negative or inconclusive with respect to the proposed hypothesis, these will be attempted to publish as scientific production in journals of high impact in the area of knowledge and indexed in Journal Citation Reports of ISI-Thompson, preferably of the 1-2th quartile. In addition, we will try to select Open Acess journals to favor the scientific dissemination of the results. In the same way, the results will be exposed in communications, papers, forums and discussion tables of different scientific and cultural days.

Patient reported outcome: Physical activity related to a person's health

Patient reported outcome. It is an evaluation of sedentary behavior. An alternative way to the use of accelerometry for the calculation of energy consumption.

Patient reported outcome. Health index that relates quantity and quality of life. It is applied with a short questionnaire and a visual analogue scale. Each dimension is rated in five levels from 1 ("I have no problem with...") to 5 ("I am unable to..."). Each participant indicates the level that best reflects their state for each of the five dimensions, with which their health status is described by five digits that take values from 1 to 5, with health status 11111 being considered a priori the best state of health and 55555 the worst state of health. The visual analogue scale is scored from 0 (without pain) to 100 (worst pain).

Patient reported outcome: tool designed to assess patient satisfaction with physiotherapy care through intrinsic and extrinsic factors. The instrument consists of 10 specific items and 2 global items scored from 1 (strongly disagree) to 5 (strongly agree). The means of items 1 through 3 and 4 through 10 are calculated to determine the mean score for external and internal subscales, respectively. Total score from 0 (worst patient satisfaction) to 5 (best patient satisfaction).

Patient reported outcome:Questionnaire designed to evaluate cancer-related fatigue in breast cancer survivors. Composed of 22 numerically scaled, "0" to "10" items that measure four dimensions of subjective fatigue: behavioral/severity, affective meaning, sensory and cognitive/mood. To calculate the total fatigue score, add the 22-item scores together and divide by 22 in order to keep the score on the same numeric "0" to "10" scale. Severity codes: 0 none, 1-3 mild, 4-6 moderate, 7-10 severe.

Patient reported outcome: quantification of existing fear-avoidance components in patients with medical conditions associated with pain. 20 question related to painful medical condition. 5 = Completely Agree 4 = Mostly Agree 3 = Slightly Agree 2 = Slightly Disagree 1 = Mostly Disagree0 = Completely Disagree. Higher values represent a worse outcome.

patient reported outcome. Assessment the degree of physical disability related to non-specific low back pain, understanding physical disability as limitation in the performance of activities of daily life.

Patient reported outcome.Assessment the functionality of the column as a whole

Brief structured diagnostic interview to generate diagnoses DSM-IV and ICD-10

Patient reported outcome. Assessment the presence and severity of depressive symptoms, relating to the last days of the previous week.

Horizon 2020 - European Commission

University of Malaga

Principal Research

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Group 1 receives three decision aids and feedback on their standardized patient (SPI) interaction rating their shared decision making skills and highlighting opportunities for improvement.

Group 2 receives three decision aids. This group does not receive any feedback from the SPI.

Group 3 receives an online, interactive webinar that focuses on SDM skills in clinical encounters and feedback on their standardized patient (SPI) interaction rating their shared decision making skills and highlighting opportunities for improvement.

Group 4 receives an online, interactive webinar that focuses on SDM skills in clinical encounters. This group does not receive any feedback from the SPI.

1 hour online, interactive webinar that covers shared decision making skills in clinical encounters.

Webinar

Participants will receive 3 decisions aids to review.

DA viewing

Rating of shared decision making skills and opportunities for improvement based on transcript of a standardized patient interaction

SPI feedback

Karen Sepucha, PhD

The Health Decision Sciences Center (HDSC) staff has deployed different approaches to training clinicians to engage patients in shared decision making for common medical tests and treatments. The purpose of the study is to compare the effectiveness of shared decision making (SDM) skills training courses using standardized patient interactions (SPI) and written evaluations.

There is limited evidence on approaches to training clinicians to engage patients in shared decision making for common medical tests and treatments. The purpose of the study is to compare the effectiveness of different approaches to shared decision making (SDM) skills training. Participants will be randomly assigned to either receive two decision aids or a webinar to review. Participants will also be randomly assigned to receive feedback on standardized patient interaction rating their shared decision making skills and highlighting opportunities for improvement or not. Clinician participants will be assigned to one of four intervention groups using a 2x2 factorial design:

Group 1: Decision aid viewing with feedback Group 2: Decision aid viewing and no feedback Group 3: webinar with feedback Group 4: webinar and no feedback

The pilot study will provide evidence on the comparative effectiveness and feasibility on training formats to determine if:

* Clinicians improved in SDM communication skills
* Clinicians have an increased confidence to use SDM with their patients
* The training is acceptable to clinicians

A Trial Comparing Approaches to Shared Decision Making Skills Training for Clinicians

A Pilot Randomized Trial Comparing Approaches to Shared Decision Making Skills Training for Clinicians

Transcripts from standardized patient interactions (SPI) will be scored using Braddock's Informed Decision Making (IDM) framework to assess shared decision making skills. Scores with the Braddock's Informed Decision Making Framework range from 0 to 9; the higher scores are better. We subtracted the scores of the baseline SPI collected before the intervention from the second SPI collected 4-6 weeks later, after the intervention, to determine the change in IDM score for each participant and then compared change scores across study arms.

Partners HealthCare

Massachusetts General Hospital

Director Health Decision Sciences Center

Group 1 receives three decision aids and feedback on their standardized patient (SPI) interaction rating their shared decision making skills and highlighting opportunities for improvement.

DA viewing: Participants will receive 3 decisions aids to review.

SPI feedback: Rating of shared decision making skills and opportunities for improvement based on transcript of a standardized patient interaction

DA Viewing With SPI Feedback

Group 2 receives three decision aids. This group does not receive any feedback from the SPI.

DA viewing: Participants will receive 3 decisions aids to review.

DA Viewing With no SPI Feedback

Group 3 receives an online, interactive webinar that focuses on SDM skills in clinical encounters and feedback on their standardized patient (SPI) interaction rating their shared decision making skills and highlighting opportunities for improvement.

Webinar: 1 hour online, interactive webinar that covers shared decision making skills in clinical encounters.

SPI feedback: Rating of shared decision making skills and opportunities for improvement based on transcript of a standardized patient interaction

Webinar With SPI Feedback

Group 4 receives an online, interactive webinar that focuses on SDM skills in clinical encounters. This group does not receive any feedback from the SPI.

Webinar: 1 hour online, interactive webinar that covers shared decision making skills in clinical encounters.

Webinar With no SPI Feedback

Total

Age, Categorical

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United States

Region of Enrollment

Karen Sepucha

Change in Braddock's Informed Decision Making Score

Overall Study

Musculoskeletal Diseases

Rare Diseases

Necrosis

Intervertebral Disc Displacement

Chronic Graft Versus Host Disease

Serum levels of pro-inflammatory cytokines were measured using the Enzyme Linked Immuno Sorbent Assay (ELISA) technique in 23 patients with pain due to herniated disk disease (G1) as well as in 10 control healthy subject

Five milliliters of venous blood was drawn in the morning from subjects and immediately centrifuged.

blood collect

Durval C Kraychet

The purpose of this study is to:

* evaluate if there is an association between elevated levels of cytokines and chronic pain due to herniated disk disease
* measured cytokines levels in chronic low back pain and in healthy subjects.

23 patients with at least three months of back pain due to herniated disk disease were selected Diagnosis was confirmed by magnetic resonance imaging (MRI) or computerized tomography (CT) imaging of the spine for all patients. In addition, pain severity had to be ³ 5 points on the Numerical Rating Scale (NRS) ranging from zero (no pain) to 10 (worst imaginable pain).

The exclusion criteria were defined as one or more of the following: psychiatric disorders, systemic or inflammatory disease, history of allergy, presence of motor deficits, history of blood dyscrasia, pregnancy, active infection, tumor, use of analgesic drugs in the week before or inability to come to the hospital for evaluation.

Study of Cytokines Serum Levels in Chronic Low Back Pain

Analytical Transversal Study of Cytokines Serum Levels in Chronic Low Back Pain Due to Herniated Disk

Federal University of Bahia

Federal University of São Paulo

Durval Campos Kraychete

No manipulative intervention. Phlebotomy for inflammatory biomarker determinations to compare acute versus chronic at baseline.

Inflammatory biomarker determinations after a course of 6 SMT interventions over the period of 2 weeks; a single SMT per treatment.

Asymptomatic subjects. Biomarker determinations at time zero and again two weeks later.

Spinal manipulation will consist of a single high velocity low amplitude thrust to a hypomobile vertebral segment determined by the treating clinician to contribute to the problem.

Spinal manipulation

H. S. Injeyan, PhD, DC

It is expected that mechanical low back pain (LBP) is associated with inflammatory changes localized to the affected tissues. Could such changes be detected in cells involved in the inflammatory process in an in vitro model? The investigators wish to test such a model to compare inflammatory markers in acute and chronic LBP patients and also examine the effect of spinal manipulative treatment (SMT) on changing the level of selected key inflammatory markers. The investigators hypothesize that:

1. Proinflammatory markers will be elevated while antinflammatory markers will be reduced in acute LBP patients relative to chronic back pain patients as well as in healthy study participants who have no LBP or any inflammatory conditions (controls).
2. SMT will cause a reduction in the production of proinflammatory markers while anti-inflammatory markers will increase relative to baseline levels as well as relative to controls

Background: Spinal manipulative treatment(SMT) may work by reducing mechanical irritation to joint tissues (1) and thereby diminishing local inflammation. Evidence for an anti-inflammatory effect of instrument-assisted SMT has been observed in an animal model (2). These findings are consistent with the recently proposed hypothesis that the origin of all pain may be associated with inflammation and augmented production of inflammatory mediators (cytokines), principally TNFα (3). TNFα plays a major role in the pathophysiology of neuropathic pain-associated inflammation (4) and has been implicated in spinal pain syndromes, including intervertebral disc-related low back pain (5, 6) and sciatica (7,8). Our recent studies demonstrated that production of inflammatory mediators is elevated in patients with chronic cervical spine pain, both in vitro and in vivo, and accompanied by up-regulation of chemokine (CC) synthesis (9).

Recent reports on clinical (10), animal (2) and human in vitro models (11) suggest that SMT may exert an anti-inflammatory effect. Thus, Song et al. (2) found that SMT reduced inflammatory neuropathic pain. Teodorczyk-Injeyan et al. (11) demonstrated a significant attenuation of pro-inflammatory cytokine production in vitro, and no changes in serum substance P (SP) levels following SMT. Other studies from our laboratory showed that SMT may enhance both the production of and the response to the immunomodulatory cytokine, IL-2, and IL-2-dependent antibody synthesis (12, 13). Reduction in serum TNFα levels has been reported for cervicogenic headache patients (n=2, case studies) (14, 15). These observations suggest that SMT effects may be transduced into cellular components of the immune system.

Thus far, the clinical relevance of the effect of SMT as a modulator of inflammatory mediator production is unknown. Despite evidence of inflammatory pathophysiology of spinal pain (16), including a subtype of non-specific spinal pain (17), only one clinical study (18) evaluated the correlation between serum TNFα levels, pain intensity and back function.

In this proposed study we intend to use a clinical model to investigate the baseline levels of proinflammatory cytokines in acute and chronic low back pain patients and explore the potential anti-inflammatory effect of SMT following a course of manipulative treatments. Thus, Aim 1 is to determine baseline pro-inflammatory cytokine levels in individuals experiencing acute or chronic lower spinal pain of mechanical etiology, and compare them with asymptomatic controls'. Aim 2 is to explore the relationships between SMT, pain level and functional impairment, and the production of inflammatory mediators relative to baseline.

Anti-inflammatory cytokines (IL-10 and IL-1ra) have been found to be produced alongside, and in parallel, with their respective pro-inflammatory counterparts (TNFα and IL-1β), and act in concert to sustain/restore homeostasis (19). The proposed study will include determinations, in addition to pro-inflammatory cytokine (IL-1, TNFα, IL-6) levels, of the levels of IL-1 receptor antagonist (IL-1ra) and IL-10. Assessment of IL-10 synthesis is particularly relevant as this cytokine up-regulates the production of IL-1ra, which competes with active IL-1 for binding to IL-1 receptors, and which acts as a potent natural anti-inflammatory protein (19, 20).

Study design; Subject Recruitment: Subjects (volunteers) of both sexes, between the ages 20 and 60 years, experiencing acute (less than 4 weeks in duration) or chronic (12 weeks or longer in duration) mechanical low back pain (experienced between spinal levels L1- L5, with or without sacroiliac \[SI\] joint involvement) will be recruited by Canadian Memorial Chiropractic College (CMCC) personnel and posters from CMCC's outpatient clinics, and from the general public through newspaper advertisements . CMCC is in the Greater Toronto Area (GTA), where the population is a diverse ethnic mix (21). Potential participants who have presented to one of the CMCC clinics for the purpose of treatment will be encouraged/recruited by interns/clinicians prior to commencement of treatments. Others who present to participate in the research study will first be assigned to one of the clinic pods for initial assessment prior to entering the study. In no case, however, will participants have received SMT 4 weeks prior to commencement of the study.

Candidates will be interviewed in order to determine eligibility (see exclusion criteria, Appendix 1). They will complete the research intake form (Appendix 2) and be given detailed explanations about the research protocol (Appendix 3). A cohort of matching healthy asymptomatic subjects, recruited from the general population, will serve as controls for the determination of baseline cytokine levels.

Sample size determination: Data published for TNFα levels in chronic neck pain patients versus asymptomatic controls (9) were used to calculate a sample size estimate for this study. The study is powered for the primary outcome measure related to Question 1, looking at the difference between symptomatic and asymptomatic low back pain subjects at baseline (see Statistical Analyses). From Cohen's table (22), based on a power of 0.8, a two-tailed test with a p value \< 0.05, the sample size was estimated to be 17 per group. In order to account for drop-outs and errors that may arise in the blood cultures, the sample size will be increased to 20 per group. As a result, there will be 40 symptomatic subjects and 20 asymptomatic controls, which should provide a more than adequate sample to test the primary outcome.

Subject assessment and group assignment: Qualified subjects will be scheduled. They will be greeted by one of two investigators (depending on recruitment site) , who will brief them and review the intake/eligibility form (Appendix 3) to confirm their eligibility before asking them to sign the informed consent form (Appendix 4). All subjects will then be asked to indicate their pain intensity level on the 10-point visual analogue scale (VAS) and complete the Oswestry functional disability questionnaire. They will then be assessed with standard chiropractic, orthopaedic and neurological tests by their respective chiropractic interns and supervising clinicians, who will assign them to the acute or chronic LBP groups, and who will formulate and explain a treatment plan.. For the duration of the study, treatments will consist of manual SMT and, where needed, manual (not instrument-assisted) soft tissue work provided by the clinician. Other treatment modalities will not be used.

Patients will receive 6 treatments over the course of 2 weeks. (comprised of manipulation of one lumbar or sacroiliac articulation, with or without soft tissue therapy). SMT will consist of a single high velocity, low amplitude (HVLA) thrust intended to cavitate and restore mobility to the joint. If at initial presentation a manipulative segment could not be identified, the patient will be excluded from the study. If on the other hand a manipulable segment is not found at subsequent visits, the clinician will limit the treatment to palpation and some soft tissue work as indicated . In all cases a blood sample will be drawn (see below) after initial assessment and prior to commencement of treatments of patients, in order to establish a baseline level of cytokines for each participant (primary outcome). At their 7th visit (at least 2 days after last treatment), a blood sample will be taken prior to commencement of any further treatment, and they will be asked to complete the exit questionnaire including a VAS (Appendix 5). Should a patient recover following a few treatments, as assessed by subjective feedback from the patient and a VAS result of less than 3/10, then a blood sample will be taken earlier and such will be duly noted. Should a patient require continued treatments beyond the 6 stipulated by the study, s/he will be free to do so under the direction of the clinician in charge of their case.

Interventions: Manipulation: As noted above, each spinal manipulation will consist of a HVLA thrust to an affected segment (23). A clinician will deliver treatments according to his/her assessment findings on a given day.

Venipuncture: On the day of admission into the study and at the completion of SMT therapy, an experienced phlebotomist will perform venipuncture using standard procedures (antecubital fossa, 21gauge needle) in the seated position. Heparinized blood samples (10 ml each) will be collected and transferred (at room temperature) to the laboratory within an hour of collection for the preparation of whole blood cultures as described below .

Laboratory studies

1. Induction of inflammatory cytokines To assess cytokine production in vitro, a whole blood (WB) culture system will be utilized (19). Briefly, multiple sets of WB cultures representing different treatment/culture conditions for each subject will be prepared. Cultures will be stimulated at initiation with 10 μg/ml lipopolysaccharide (LPS) for the induction of TNFα and IL-1β production. Phytohemagglutinin (PHA, 10 µg/ml) alone and in combination with LPS will be used to induce production of the anti-inflammatory cytokine, IL-10 and 2 chemokines, CCL2 and CCL3 . Cultures will be maintained at 37C (Celsius) in a humidified 5% C02 incubator. As clinical conditions involving inflammatory responses may cause a time shift in the capacity for cytokine production (19, 27), the levels of the studied mediators (TNFα, IL-1β, IL-1ra, IL-10, CCL2 and CCL3) will be examined at 24 h intervals in culture supernatants harvested between 24-72h post-initiation. Aliquots of the supernatants will be stored at -76C (Celsius) until tested. This model will allow investigation of the relation between the releases of pro- and anti-inflammatory mediators.
2. Determinations of cytokine levels by enzyme-linked immunosorbent assay The levels of TNFα, IL-1β , and IL-10 and IL-1ra in supernatants from whole blood cultures will be determined by specific enzyme-linked immunosorbent assays (ELISA) using DuoSet ELISA development system for natural and recombinant human cytokines (R\&D Systems, Minneapolis, MN) as described previously (9, 11), and Quantikine Immunoassay Kits will be used for CCL2 and CCL3 determinations. All immunoassay procedures, including reagent and sample diluent preparations, will be carried out as per manufacturer's recommendations. Each of the studied samples will be tested at least twice at 2-4 different dilutions.

Statistical analyses All of the studied mediators will be measured for the LBP patients and asymptomatic subjects at baseline and at the completion of the treatment period. For Question 1 (the primary outcome), baseline comparison for each TNFα and IL-1β will be compared between symptomatic subjects (acute and chronic) versus asymptomatic control subjects. Two unpaired t-tests will be used to test the associated hypothesis. For Question 2, the mean pre-post difference scores will be compared for each of TNFα and IL-1β between the three groups (acute, chronic and asymptomatic) using an ANOVA. If baseline values are significantly different between groups (as hypothesized from Question 1), then ANCOVA will be used to account for this difference. It is anticipated that the sample size is sufficiently large to accommodate this analysis. However, after determining the results for Question 2, a power analysis will be completed. If the study is insufficiently powered for this question, then another sample size estimate will be calculated to inform future work.

For other pro-inflammatory and anti-inflammatory cytokines measured in this study, regression modeling will be used in an attempt to predict cytokine responses. It is understood that any model created during this process will need to be confirmed in a future investigation. Both models created and descriptive data derived from the investigation will be used to inform future work.

Time frame Based on experience, up to 5 subjects per week can be tested. However, based on condition prevalence, we project that patient recruitment and sample collection will take 8-12 months. Cytokine level determinations in cell cultures derived from the three groups of participants will lag behind by 3-4 months, and data analysis will be completed within another 2 months. Preparation of manuscripts will require an additional 4-6 months. Thus we anticipate completing this project within 18 -24 months of initiation of the study.

Effects of Spinal Manipulative Treatment on Inflammatory Markers in Low Back Pain Patients

Changes in Inflammatory Cytokine Levels in Response to Spinal Manipulative Treatment of Low Back Patients: A Single-blind Pilot Clinical Trial.

Parallel bioassays will be done on samples from the same culture supernatants in order to determine the levels of antiinflammatory mediators and chemokines. Changes in the levels of these mediators in response to manipulative treatment may be correlated to changes in proinflammatory mediator levels. Results will be calculated as the difference between baseline and endpoint (i.e. end of two week treatment period).

Supernatants from whole blood cultures are collected 24 or 48 hours postincubation, are dispensed in 0.5-1.0 ml aliquots and stored at 76C. Because subject recruitment occurs over a long period,it is not desirable to process samples sporadically. This approach allows using same-batch reagents/bioassay kits for all samples in an effort to decrease error and enhance internal consistency. Results will be expressed as the difference between the values obtained for acute, chronic and control at baseline.

Postintervention samples (whole blood culture supernatants) will be aliquoted and stored at -76C. proinflammatory cytokine levels will be compared to their respective baselines as well as the asymptomatic controls. These samples will be processed along with those for the primary outcome measure. Results will be expressed as the difference between baseline and endpoint (i.e. end of two week treatment period).

Canadian Memorial Chiropractic College

Professor and Chair Department of Pathology and Microbiology

Sciatica

Sciatic Neuropathy

Mononeuropathies

Peripheral Nervous System Diseases

Neuromuscular Diseases

Neuralgia

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Gastrointestinal Agents

All Drugs and Chemicals

Etanercept

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Immunosuppressive Agents

Immunologic Factors

Two injections of epidural saline 2 weeks apart

Two injections of epidural etanercept 2 weeks apart

2 injections of etanercept 2 weeks apart with doses ranging from 2 mg to 6 mg

epidural injection of etanercept

placebo (control procedure)

Steven P Cohen, MD

Tumor necrosis factor (TNF)-alpha has been strongly implicated as a major contributing factor for the development of radiculopathy. In animal studies, the application of TNF-alpha to nerve roots results in pain behavior indicative of radiculopathy. The use of TNF-alpha inhibitors (etanercept and infliximab) have been shown to prevent this pain behavior. Open-label studies in humans have shown both etanercept and infliximab provide excellent, long-term relief in patients with acute radiculopathy from herniated disc. However, a recent placebo-controlled study failed to demonstrate any significant difference from placebo. The investigators have already established the safety of neuraxial etanercept in a trial that has just been completed (not yet published). The objective of this study is to determine whether small doses of epidural etanercept, an anti-TNF-a medication, is an effective treatment for LBP caused by nerve root irritation (i.e., radiculopathy).

As per the wishes of the Dept. of the Army and Walter Reed Army Medical Center Dept. of Clinical Investigation, patients will be randomized in a 3:1 ratio to receive 2 transforaminal epidural etanercept or saline injections at 2-week intervals. Both patients and physicians will be blinded as to the injectate and treatment group. There will be 3 study groups. Group I will receive either 2 mg of etanercept or saline per injection. Group II will receive either 4 mg of etanercept or saline per injection. Group III will receive either 6 mg of etanercept or saline per injection. In each group there will be 8 patients: 6 who receive etanercept and 2 who receive saline. As per a previous study we just completed, etanercept doses will not be escalated until all 6 patients have completed their 1-month follow-up visits without any evidence of toxicity or complications.

Efficacy of Epidural Etanercept in the Treatment of Sciatica

Walter Reed Army Medical Center

Johns Hopkins University

Steve P. Cohen

Chronic Pain

NKTR-181 tablets 100-600 mg twice daily (BID)

NKTR-181 BID tablets

The purpose of this 52-week open label study is to determine the long-term safety of a new opioid molecule, NKTR-181, in patients with moderate to severe chronic low back pain or chronic non-cancer pain.

This is an open-label safety and tolerability study in which approximately 600 subjects will receive NKTR-181 for up to 52 weeks. Subjects may include newly enrolled subjects and subjects who have recently completed SUMMIT-07 study.

This study will also investigate the pharmacokinetics of NKTR-181 in patients with chronic low back pain or chronic non-cancer pain.

Long-Term Safety and Tolerability Study of NKTR-181 in Subjects With Chronic Low Back Pain or Chronic Non-Cancer Pain

A Phase 3 Multicenter, Open-Label, 52-Week Study To Evaluate the Long-Term Safety and Tolerability of NKTR-181 in Subjects With Moderate to Severe Chronic Low Back Pain or Chronic Non-Cancer Pain

Count of subjects reporting treatment emergent adverse events

A self-reported scale measuring severity of pain on function. The mean of the 4 intensity items (3-6) is calculated and used as a measure of pain severity. If there were missing items when the pain severity score was calculated, the mean of the completed items in one dimension (dimensions include pain severity and pain interference) were imputed to substitute the missing item, provided that more than 50% of the items in one dimension were completed (Halling, 1999). The range of pain intensity and interference for each question is from 0 to 10. The range of possible scores is from 0 to 70. Higher score indicates relatively worse pain severity and greater interference that pain causes in day to day activities.

A self-reported scale measuring interference of pain on function. The mean of the 7 interference items was calculated and used as a measure of Pain interference. If there were missing items when the pain interference score was calculated, the mean of the completed items in one dimension (dimensions include pain severity and pain interference) were imputed to substitute the missing item, provided that more than 50% of the items in one dimension were completed (Halling, 1999). The range of pain interference is from 0 to 10. Higher score indicates relatively worse pain problem.

Nektar Therapeutics

Adverse events were collected after the subject provided written informed consent through the end of study. Adverse event data were obtained via spontaneous reports or per direct questioning or observation during protocol-mandated study assessments. All ongoing AEs were followed until resolution or for 14 days after the subject's last visit, whichever came first. All SAEs were followed until resolution, stabilization of condition, return to baseline, or until follow-up was no longer possible.

Subjects administered NKTR-181 in preceding phase 3 efficacy/safety study

Rollover NKTR-181

Subjects administered placebo in preceding phase 3 efficacy/safety study

Rollover PBO

Newly enrolled opioid experienced subjects

De Novo Opioid Experienced

De Novo Naive

Age, Continuous

Race (NIH/OMB)

Safety Analysis Set is defined as all enrolled subjects who received at least 1 dose of study drug.

Medical Affairs

Number of Participants Reporting Adverse Events

Pain Intensity: Baseline

Pain Intensity: Change from Baseline to Day 1

Pain Intensity: Change from Baseline to Day 30

Pain Intensity: Change from Baseline to Day 60

Pain Intensity: Change from Baseline to Day 90

Pain Intensity: Change from Baseline to Day 120

Pain Intensity: Change from Baseline to Day 150

Pain Intensity: Change from Baseline to Day 180

Pain Intensity: Change from Baseline to Day 210

Pain Intensity: Change from Baseline to Day 240

Pain Intensity: Change from Baseline to Day 270

Pain Intensity: Change from Baseline to Day 300

Pain Intensity: Change from Baseline to Day 364

Change From Baseline in Brief Pain Inventory (BPI) Pain Intensity Item to Week 52

Pain Interference: Baseline

Pain Interference: Change from Baseline to Day 1

Pain Interference: Change from Baseline to Day 30

Pain Interference: Change from Baseline to Day 60

Pain Interference: Change from Baseline to Day 90

Pain Interference: Change from Baseline to Day 120

Pain Interference: Change from Baseline to Day 150

Pain Interference: Change from Baseline to Day 180

Pain Interference: Change from Baseline to Day 210

Pain Interference: Change from Baseline to Day 240

Pain Interference: Change from Baseline to Day 270

Pain Interference: Change from Baseline to Day 300

Pain Interference: Change from Baseline to Day 364

Change From Baseline in Brief Pain Inventory (BPI) Pain Interference Item to Week 52

NKTR-181 tablets at 100-600 mg orally twice daily

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Digital Intervention for the Modification of Lifestyles (iGame)	NCT04019119	Low Back Pain Oncology Depression Sedentary Lifes... Sedentary Behav...	Digital interve...	18 Years - 65 Years	University of Malaga
A Trial Comparing Approaches to Shared Decision Making Skills Training for Clinicians	NCT02871739	Depression Low Back Pain	Webinar DA viewing SPI feedback	18 Years -	Massachusetts General Hospital
Digital Intervention for the Modification of Lifestyles (iGame)	NCT04019119	Low Back Pain Oncology Depression Sedentary Lifes... Sedentary Behav...	Digital interve...	18 Years - 65 Years	University of Malaga
Study of Cytokines Serum Levels in Chronic Low Back Pain	NCT00991042	Interleukines	blood collect	20 Years - 65 Years	Federal University of São Paulo
Effects of Spinal Manipulative Treatment on Inflammatory Markers in Low Back Pain Patients	NCT01766141	Low Back Pain	Spinal manipula...	20 Years - 60 Years	Canadian Memorial Chiropractic College
Efficacy of Epidural Etanercept in the Treatment of Sciatica	NCT00364572	Sciatica	epidural inject... placebo (contro...	18 Years - 70 Years	Johns Hopkins University
Study of Cytokines Serum Levels in Chronic Low Back Pain	NCT00991042	Interleukines	blood collect	20 Years - 65 Years	Federal University of São Paulo
A Trial Comparing Approaches to Shared Decision Making Skills Training for Clinicians	NCT02871739	Depression Low Back Pain	Webinar DA viewing SPI feedback	18 Years -	Massachusetts General Hospital
Long-Term Safety and Tolerability Study of NKTR-181 in Subjects With Chronic Low Back Pain or Chronic Non-Cancer Pain	NCT02367820	Low Back Pain Chronic Pain	NKTR-181 BID ta...	18 Years - 75 Years	Nektar Therapeutics
A Trial Comparing Approaches to Shared Decision Making Skills Training for Clinicians	NCT02871739	Depression Low Back Pain	Webinar DA viewing SPI feedback	18 Years -	Massachusetts General Hospital

Spots Global Cancer Trial Database for low back pain