Nervous System Diseases

All Conditions

Symptoms and General Pathology

Neoplasms

Peripheral Nervous System Diseases

Pain

Hyperalgesia

Paraneoplastic Polyneuropathy

Polyneuropathies

Neuromuscular Diseases

Syndrome

Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

Nervous System Neoplasms

Neurodegenerative Diseases

Sham therapy device to area of painful chemotherapy induced peripheral neuropathy (CIPN) for 45 minutes daily x 10 days

MC-5A therapy to the area of painful CIPN for 45 minutes daily for a total of 10 days.

45 minutes daily x 10 treatments (given over the course of 2 weeks)

MC-5A

Sham therapy daily x 45 minutes for 10 treatments (given over course of 2 weeks)

Sham device

Tony Campbell

Painful chemotherapy induced peripheral neuropathy (CIPN) is a common complication of cancer therapy with few treatment options. CIPN is a complex side effect that varies between individuals and can be difficult to describe, difficult to treat and can significantly effect quality of life for patients.

The purpose of this study is to determine if patients with painful CIPN will have a decrease in pain scores after treatment with the MC-5A device.

MC-5A for Chemotherapy Induced Peripheral Neuropathy

Treatment of Painful Chemotherapy -Induced Peripheral Neuropathy With the MC-5A Pain Therapy Medical Device, a Randomized, Double-Blind, Sham-Controlled Clinical Trial

Pain levels will be compared as measured by changes in mVAS, and quantified and tested for normal distribution. If normally distributed, parametric test (i.e., two-sample t-test) will be used; p-values \<0.05 will be considered statistically significant. If changes in mVAS are not normally distributed, non-parametric testing such as Wilcoxon rank-sum will be performed. VAS is measured at 3 time points.

mVAS and deficits scale are used to obtain continuous quantitative information about positive and negative sensory phenomena during application of QSPT stimulation.

Patients provide rating of positive sensory phenomena using mVAS if the stimulus at the pain test site is increased or painful when compared to normal control site. Rating on mVAS is obtained by instructing the patient to pull out the mechanical scale with millimeters (looks like a slide ruler) to reflect intensity of any painful sensation on a scale of 0 - 10, with 10 being the worst. Score = Visit - Baseline.

The number of participants experiencing adverse events, as defined by CTCAE

University of Wisconsin, Madison

This study uses the CTCAE v.4 definition of adverse event, which does not differ from the clinicaltrials.gov definitions.

Sham therapy device to area of painful chemotherapy induced peripheral neuropathy (CIPN) for 45 minutes daily x 10 days

Sham device: Sham therapy daily x 45 minutes for 10 treatments (given over course of 2 weeks)

Sham Device

MC-5A therapy to the area of painful CIPN for 45 minutes daily for a total of 10 days.

MC-5A: 45 minutes daily x 10 treatments (given over the course of 2 weeks)

MC-5A Treatment

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

The small sample size is subject to type II error. The estimated effect size for MC5A is high: the company estimates 100% of patients will respond. Thus our power calculations suggested a small sample could still detect a difference.

Toby Campbell

Visit 1 (Day 1)

Visit 10 (Day 10)

End of Study (Week 12, +/- 2 weeks)

The number analyzed differs per row as some participants dropped out or did not receive all 10 treatments. For example, on the Sham Device arm, only 4 participants were treated on day 10 but 5 returned for the final visit. Because this was a pilot study, all participant data was analyzed and is included here.

Change in Mechanical Visual Analog Scale (mVAS) Using Quantitative Sensory Pain Testing (QSPT)

Adverse Events

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Somatosensory Disorders

Sensation Disorders

Neurologic Manifestations

Analgesics

Central Nervous System Depressants

All Drugs and Chemicals

Anti-Infective Agents

Anti-Dyskinesia Agents

Cardiotonic Agents

Amino Acids

Analgesics, Opioid

Amantadine

N-Methylaspartate

Antiparkinson Agents

Antiviral Agents

Dopamine

Dopamine Agents

Neurotransmitter Agents

Analgesics, Non-Narcotic

Aspartic Acid

Lucia Gagliese, PhD

Vincent Chan, MD

Dirk Snijedelaar, MD

Joel Katz, PhD

Gideon Koren, MD

The primary aim is to determine whether perioperative NMDA-receptor antagonism has differential effects on postoperative pain, hyperalgesia and morbidity in younger and older patients. In order to achieve this aim, the researchers propose to conduct the first randomized, double-blind placebo-controlled study designed to investigate age differences in the effects of perioperative oral administration of an NMDA-receptor antagonist (amantadine) in men undergoing radical prostatectomy. In addition, age differences in psychosocial factors and the pharmacological properties of amantadine and morphine will be measured to control for, and clarify, their contribution to the differences found.

The specific objectives of the study are to:

1. investigate the effects of perioperative NMDA receptor blockade on postoperative hyperalgesia, pain and analgesic consumption in young and elderly men
2. assess age differences in the intensity and course of secondary hyperalgesia after surgery

The immediate postoperative period is associated with spontaneous pain and hyperalgesia, i.e., increased pain response (both intensity and duration) to normally painful stimuli following tissue injury or damage.

The development and maintenance of secondary hyperalgesia depend on complex plastic changes in spinal cord dorsal horn cells after peripheral injury or damage. Afferent impulses signaling the damage are carried to the dorsal horn by slowly conducting, unmyelinated C-fibres. C-fibres release glutamate which acts at three receptor types: metabotropic, kainate/AMPA and NMDA. NMDA receptor activation, through a complex cascade of intracellular events, results in dorsal horn neuron hyperexcitability or central sensitization. These cells have increased spontaneous activity, decreased threshold, increased response to afferent input, prolonged afterdischarge to repeated stimulation, and an expansion of receptive fields. Central sensitization is expressed behaviorally as secondary hyperalgesia and contributes to prolonged postoperative pain. It also may trigger pathological reorganization of neural circuitry leading to the development of chronic postsurgical pain. Through these processes, tissue injury may have profound effects on the CNS that long outlast the injury.

In animal models of pain, NMDA agonists induce central sensitization and hyperalgesia whereas antagonists decrease or prevent hyperalgesia. In humans, NMDA-receptor antagonism decreases secondary hyperalgesia subsequent to experimentally-induced pain.

Perioperative administration of NMDA antagonists, that is, before, during and after surgery, may be the ideal intervention to block the initiation and maintenance of central sensitization. Several studies have found that this intervention reduces postoperative hyperalgesia, pain, and analgesic use; however, others have not found these effects. This is not surprising given the variability across studies in factors such as surgical procedure, extent and nature of tissue damage, duration of surgery, pharmacokinetics of the agent(s) tested, and intraoperative and postoperative analgesia. Nonetheless, the weight of the evidence suggests that preventing or minimizing central sensitization reduces pain and analgesic requirements.

Co-administration of NMDA antagonists and opioids has been advocated as an effective approach. The combination of morphine and amantadine should reduce postoperative pain by inducing analgesia through actions on opioid-mediated receptor systems and by reducing hyperalgesia via NMDA receptor-mediated events . The combination also should produce fewer opioid-related adverse effects due to the anticipated opioid-sparing effect. The present proposal describes the first direct comparison of perioperative NMDA receptor blockade coupled with intra- and post-operative opioid administration in young and elderly patients. In order to minimize the influence of other perioperative factors on the outcome variables, all patients will undergo the same surgical procedure and anesthetic protocol. Furthermore, factors that cannot readily be standardized (e.g., surgical duration, mood) will be measured and controlled for statistically. This increases the internal validity of the proposed study and our ability to detect age and drug effects.

Effects of N-Methyl-D-Aspartate (NMDA)-Receptor Antagonism on Hyperalgesia, Opioid Use, and Pain After Radical Prostatectomy

Effects of NMDA-Receptor Antagonism on Hyperalgesia, Opioid Use, and Pain After Radical Prostatectomy in Young and Elderly Patients

Canadian Institutes of Health Research (CIHR)

University Health Network, Toronto

Rare Diseases

Chronic Pain

Chronic Graft Versus Host Disease

Patients in this arm will take part in the clinical multidisciplinary opioid tapering program (MTP).

As above, though patients in this group will also take part in an opioid education workshop

The comprehensive workshops will include a combination of didactic and interactive content on general pain and opioid education (1 hour workshop session to be co-presented by Drs Ryan Amadeo and Dana Turcotte) along with significant psychological content (co-presented by Drs Brigitte Sabourin and Gregg Tkachuk) making up the remainder of the day-long workshop. Content presented in PEWs will include opioid-related risks, identifying personal motivation for (or barriers to) tapering, goal setting, pain self-management, sleep hygiene and comprehensive focus on ACT and rethinking pain. During the interprofessionally co-facilitated sessions, participants will be provided with workbooks that will contain session specific content as well as take-home activities and information for their own personal use.

Patient Education Workshop (PEWs)

The MTP will begin with a Baseline Tapering Visit and will include the same baseline health and well-being questionnaires, a medication review, relevant pain history, relevant opioid use history, discussion re: patient-specific tapering and functional goals, taper start date, and determination if a different opioid formulation will be required for the taper. A detailed taper plan will be prepared and reviewed by the study clinician(s) and provided to the patient. In general, tapers will begin with a 10% reduction of dose every 2 weeks until ⅓ of the original dose is met, or until taper goal has been met. If further tapering is planned once the patient reaches ⅓ of their original dose, the taper will be reduced to half the volume and rate noted above in order to improve tapering success.

Tapering plans and approaches may be changed (slowed, increased, halted etc.) based on follow up.

Multidisciplinary Tapering Program

Chronic pain management is complex, with healthcare providers historically relying on prescribing opioid medications such as morphine. Although opioids may partially improve pain, there are risks associated with them as well, including pain worsening, side effects, addiction and overdose. It is now understood that the management of chronic pain is more effective when multiple healthcare team members work together and incorporate multiple strategies instead of focusing solely on medications. An example of an effective, non-drug strategy for pain is a service offered by clinical psychologists called "Acceptance and Commitment Therapy" - or ACT - which empowers individuals, to implement alternative ways of thinking about and reacting to pain and its effect on their lives.

Canada has responded to the opioid overdose crisis with new guidelines that encourage physicians and those suffering from chronic pain to aim for lower opioid doses whenever possible, a process often referred to as "tapering." Unsurprisingly, tapering opioids is often difficult for patients to consider, primarily due to misconceptions that it will cause more harm than good.

This project aims to address these misconceptions by developing and offering an all-day educational workshop for patients, co-presented by a healthcare team (clinical psychologists, pharmacists and physicians), to provide in-depth information on opioid related risks and misconceptions, as well as a large component focusing on ACT training. Investigators then want to see if these sessions change individual attitudes towards opioid tapering and if it improves willingness and ability to successfully reduce opioid doses to a safer level.

Study Objectives:

1. To evaluate the impact of a patient-centered, multidisciplinary opioid tapering program on overall opioid consumption in individuals with chronic pain on long-term opioid therapy.
2. To implement opioid patient education workshops to be used in conjunction with the opioid tapering program and evaluate their preliminary feasibility and overall patient acceptance.

As Canada continues to witness a growing opioid crisis, the role of non-opioid medications and non-pharmacological strategies for pain, including behavioral treatments, is becoming more apparent. There is a great need to develop multidisciplinary clinical programs to assist individuals on long term opioid therapy to safely and effectively taper to safer doses of these potentially harmful medications. The use of nonpharmacological modalities will be integral to this process.

All patients enrolled in this project will be given the opportunity to take part in an informed and targeted multidisciplinary opioid tapering program (MTP). As well, half of the study population will be randomly assigned to also take part in a comprehensive opioid education and chronic pain workshop (Patient Education Workshop; PEW).

Abbreviated Methodology:

Individuals on LTOT at recruitment sites will be informed about the project by a member of their care team and those who show interest will be contacted and screened based on inclusion/exclusion criteria. Those who meet these criteria and consent to participate will be randomized to either the PEW + MTP cohort or the MTP only cohort. Depending on randomization, patients will then be invited to first attend a PEW or to attend a care visit to begin their tapering program. Participants completing the workshop will then begin the same tapering program at the MTP only cohort.

Multidisciplinary Tapering Program: Participants who have completed the Informed Consent Form ("MTP + PEW" and "MTP only" cohorts) will be included in the MTP, which will be conducted in collaboration with the patient's referring physician. All referring physicians from recruitment sites will be made aware of their role requirements in this study should their patients continue on to the MTP phase. Tapering programs will be individualized for all patients based on their current dose of opioid and clinical picture, and tapering planning will be co-managed by Drs. Amadeo and Turcotte, with the implementation and monitoring assistance of Pain Clinic nurses and Karin Ens (Clinical Pharmacist - ACCESS Winnipeg West). All participants will be asked to complete a battery of self-report measures of pain disability, pain, depression, anxiety, quality of life, pain acceptance, and valued living prior to the initiation of their tapering program (Baseline Visit) and again at 3-, 6-, and 12-month follow-up periods. Follow up has been identified as a crucial component of the MTP and will be managed by the clinical study team and clearly outlined in the detailed taper plan provided to referring physicians. Tapering plans and approaches may be changed (slowed, increased, halted etc.) based on results of this follow up at the discretion of study clinicians. Any changes/updates discussed with participants will be communicated to the referring physician with updated prescription or schedule changes. Like the tapering plan, the follow-up will be flexible and will depend on the patient's response to reductions and subsequent rate of taper. Follow up will include a combination of in-person and phone visits.

Patient Education Workshops: PEWs will be held as a full day session (approximately 9:30am to 3:30pm) and offerings will alternate between weekday and Saturday options to ensure flexibility for participants. Sessions will be offered monthly, or more often if the demand exists. The PEWs have been developed through a highly collaborative and interprofessional process and include some adaptations of previous work (used with permission) in order to create a session that is multidisciplinary, patient-centred and applicable to various forms of CNCP. The comprehensive workshops will include a combination of didactic and interactive content on general pain and opioid education (1 hour workshop session to be co-presented by Drs Ryan Amadeo and Dana Turcotte, and Karin Ens) along with significant psychological content (co-presented by Drs Brigitte Sabourin and Gregg Tkachuk) making up the remainder of the day-long workshop. Content presented in PEWs will include opioid-related risks, identifying motivation for (or barriers to) tapering, goal setting, pain self-management, sleep hygiene and comprehensive focus on ACT and rethinking pain. During the interprofessionally co-facilitated sessions, participants will be provided with workbooks that will contain session specific content as well as take-home activities and information for their own use.

Study Significance: The project will develop educational material aimed at furthering the understanding of both appropriate and inappropriate opioid prescribing in CNCP. This material will be available for consumption, beyond the project, with the knowledge users described. This will be undertaken at academic conferences, as well as at administrative gatherings in both academic and clinical settings. The knowledge created from this project, both in the program undertaken as well as in the collection and analysis of the endpoints outline, will allow for improved dialogue at all levels of health care. Both in the care of individual patients and in the public health approach to LTOT and opioid weaning, there will be improved understanding and process that will be accessible in broader primary care environments.

Patients will be randomized to either Multidisciplinary Tapering Program Only or Patient Education Workshops PLUS Multidisciplinary Tapering Program

Evaluation of a Patient-Centred, Multidisciplinary Opioid Tapering Program for Individuals With Chronic Non-Cancer Pain on Long Term Opioid Therapy

Using morphine equivalent doses, changes in opioid use will be evaluated

Using VAS tool, changes in pain will be evaluated

University of Manitoba

Assistant Professor

Skin and Connective Tissue Diseases

Recurrence

Breast Neoplasms

Pain, Postoperative

Nausea

Vomiting

Postoperative Nausea and Vomiting

Postoperative Complications

Signs and Symptoms, Digestive

Acute Graft Versus Host Disease

Adjuvants, Anesthesia

Anti-Arrhythmia Agents

Antihypertensive Agents

Anesthetics

Fentanyl

Esmolol

Metoprolol

Adrenergic beta-Antagonists

Narcotics

Adrenergic Agents

Anesthetics, Intravenous

Anesthetics, General

Adrenergic Antagonists

Adrenergic beta-1 Receptor Antagonists

Instead of narcotics (fentanyl), esmolol and lopressor are being used for hemodynamic control

Use of esmolol and metoprolol compared to use of fentanyl for hemodynamic control during general anesthesia. At induction, fentanyl (2 mcg/kg) is replaced by esmolol (1 mg/kg). During the case, with a standardised anesthesia, response to surgical stimulation will be medicated either by fentanyl (50 mcg aliquot) or metropolol (2.5 mg), for a maximum of 6 doses. After this, fentanyl will be given unblindly.

fentanyl

esmolol is used at induction and lopressor during surgery instead of fentanyl in response to surgical stimulation.

beta-blocker (esmolol, metropolol)

Etienne de Medicis, MD MSc

The first hypothesis of the study is that substituting fentanyl by esmolol and metoprolol during general anesthesia for patients undergoing mastectomy will result in less pain and less narcotic consumption in the recovery room. The investigators will also verify the impact of that substitution on nausea and vomiting, on the time spent in the recovery room and on chronic postsurgical pain (3 and 6 months).

Finally, the investigators will see the impact on breast cancer recurrence 5 years after the surgery.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
MC-5A for Chemotherapy Induced Peripheral Neuropathy	NCT01261780	Neuropathy, Par...	MC-5A Sham device	18 Years -	University of Wisconsin, Madison
MC-5A for Chemotherapy Induced Peripheral Neuropathy	NCT01261780	Neuropathy, Par...	MC-5A Sham device	18 Years -	University of Wisconsin, Madison
Effects of N-Methyl-D-Aspartate (NMDA)-Receptor Antagonism on Hyperalgesia, Opioid Use, and Pain After Radical Prostatectomy	NCT00188383	Hyperalgesia Pain Prostate Cancer	Amantadine	18 Years - 80 Years	University Health Network, Toronto
Evaluation of a Patient-Centred, Multidisciplinary Opioid Tapering Program for Individuals With Chronic Non-Cancer Pain on Long Term Opioid Therapy	NCT04902547	Opioid Use Opioids; Harmfu... Hyperalgesia Pain, Chronic	Patient Educati... Multidisciplina...	18 Years -	University of Manitoba
Postoperative Analgesia Impact of Narcotic Free Anesthesia	NCT01544959	Pain, Postopera... Breast Cancer Postoperative N...	fentanyl beta-blocker (e...	18 Years - 65 Years	Université de Sherbrooke
Effects of N-Methyl-D-Aspartate (NMDA)-Receptor Antagonism on Hyperalgesia, Opioid Use, and Pain After Radical Prostatectomy	NCT00188383	Hyperalgesia Pain Prostate Cancer	Amantadine	18 Years - 80 Years	University Health Network, Toronto

Spots Global Cancer Trial Database for hyperalgesia

Every month we try and update this database with for hyperalgesia cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.