Symptoms and General Pathology

All Conditions

Behaviors and Mental Disorders

Rare Diseases

Pain

Quality of Life

Chronic Graft Versus Host Disease

Adjuvants, Anesthesia

Analgesics

Central Nervous System Depressants

All Drugs and Chemicals

Antitussive Agents

Respiratory System Agents

Fentanyl

Oxycodone

Morphine

Hydromorphone

Methadone

Analgesics, Opioid

Tramadol

Tapentadol

These patients should have been treated only with one opioid (morphine, oxycodone, fentanyl, methadone, hydromorphone, tapentadol or tramadol) for more than one month

Chronic non-cancer pain patients not treated with analgesics

Per Sjøgren, Proff.

The primary aim is to investigate the dose and time dependent effects of different opioids on the immune and endocrine systems.

The secondary aim is to investigate whether associations between the function of the immune and endocrine systems and opioid use influence cognitive function, pain and quality of life.

BACKGROUND

Epidemiological data from the US and Denmark have shown that 3-5% of the population use opioids for treatment of chronic pain conditions.

Long-term use of opioids may cause "classic" opioid-induced adverse effects, but also serious consequences such as hyperalgesia, cognitive disorders, and suppression of the immune and endocrine systems.

Relatively few studies suggest that these substances affect hormone function in humans. The best studied is the circumstances regarding sex hormones.

A single systematic study and several clinical observations suggest that both pituitary-adrenal function and formation of growth hormone is also reduced by opioids.

Other studies have shown that not only are hormones changing during treatment with opioids, but the immunological function is also affected. There have been shown a link between the immunological and hormonal function so that parts of the immune system also affect the pituitary-adrenal function.

Opioid use and misuse per se has long been suspected to be associated with infections because both the innate and the adaptive immune system are getting affected through a number of mechanisms.

This study investigates the possibility of hormonal disorders being contributing factor to the development of cognitive impairment in patients who are in opioid treatment. The same applies to patients' well-being, mood and pain perception.

STUDY DESIGN

A cross-sectional study will be carried out at Multidisciplinary Pain Centre, Rigshospitalet, investigating opioid treated chronic non-cancer patients. These patients should have been treated only with one opioid for more than one month and will be compared to an age, educational and sex matched control group of chronic non-cancer patients not treated with analgesics.

STUDY SAMPLE

The study is an explorative study of 25 opioid treated patients and 25 controls.

The patients will be included or excluded for either group on the basis of specific criterions.

If the hypotheses of the study seem to be confirmed more patients will be included in order to investigate the effects of different opioid substances.

METHOD

Data will be collected by a trained medical student, who will administer the instruments and retrieve information from the patients' files.

Hormone assay

The adrenocortical function will be tested with the 30 min ACTH test. Leydig-cell function, IGF, TSH, thyroxine and prolactine will be measured as well.

Immunology Fresh whole blood will be used for flow cytometry, where the amount of the different cells in the immune system will be measured. Furthermore, plasma samples (snap frozen) will be collected (biobank).

The following cell types will be analyzed by using flow cytometry: NK cells, B cells and T cells. To study the immune response fresh whole blood will be stimulated with pathogens. Production of cytokines will be examined by analyzes of culture supernatants. Possible alteration in inflammation will be determined by analysing the plasma samples.

Establishment of research biobank

All material is collected as part of the study. A biobank will be established and blood samples will be safely stored at Rigshospitalet as long as the study is going on. The purpose of the research biobank is to use the samples in follow-up studies.

Assessment of cognitive function

Regarding neuropsychological assessment, two instruments were selected:

1. CRT measures sustained attention or vigilance. It is a computer test, in which through headphones, 100 auditory signals are delivered to the patient at random intervals. The patient is instructed to press a button as soon as the sound is heard.
2. DST assesses attention/concentration, recent and working memory. Patients are asked to repeat the series of numbers of increasing lengths, in both forward (direct) and backward (reverse) order.

Pain evaluation

Patients' pain intensity will be assessed using the Brief Pain Inventory (BPI) measuring pain at its worst, least and average during the last 24 hours and the current pain intensity.

Mood

Depression and anxiety will be evaluated using the Hospitality Anxiety and Depression Scale (HADS). Scores above 8 indicates that a depressive or anxiety disorder is likely to be present.

Health-related quality of life

The Short Form 36 (SF-36) will also be included in the self-administered questionnaire. The SF-36 is a 36-item survey that measures eight dimensions of health. Higher scores on the SF-36 (range 0 to 100) indicate better health-related quality of life.

RESULTS

The results will be analysed by using specific statistic tools as descriptive variables, primary outcome, secondary outcome, significance levels, and clinical significance.

The Immune and Endocrine Systems in Chronic Non-cancer Patients Treated With Opioids

The Immune and Endocrine Systems in Chronic Non-cancer Patients Treated With Opioids: Effects on Cognition, Pain and Quality of Life

Differences on the mean results of endocrine and immunologic blood tests between patients and controls, considering dose and time dependent effects.

Differences on the mean scores of the cognitive tests, pain intensity and quality of life between patients and controls.

Rigshospitalet, Denmark

Professor, M.D., Dr. Med. Sci

Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

Gastrointestinal Agents

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Androgens

Pancrelipase

Pancreatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Hormones

Hormone Antagonists

Dose Escalation: To find the dose of enzalutamide that can be safely given with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer.

Dose Expansion: To find the effect on tumor of the combination of enzalutamide, gemcitabine and nab-paclitaxel.

The starting dose of enzalutamide will be 80 mg (Level 1) daily, taken orally. The dose escalation schedule is a standard 3 + 3 design. In the first part of the study, different doses of enzalutamide will be tested. In the second part of the study, all patients will be started at the same dose of enzalutamide.

Enzalutamide

The starting dose of gemcitabine will be 1000 mg/m\^2 administered intravenously on days 1, 8 and 15 of each cycle.

The starting dose of nab-paclitaxel will be 125 mg/m\^2 administered intravenously on days 1, 8 and 15 of each cycle.

Nab-paclitaxel

Richard Kim, M.D.

The main purpose of this study is to find out the dose of enzalutamide that can be safely given with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer. Researchers also want to find out the side effects of these drugs when given together. This study will help in finding out the effect on tumor of the combination of enzalutamide, gemcitabine and nab-paclitaxel. In the first part of the study, different doses of enzalutamide will be tested. In the second part of the study, all patients will be started at the same dose of enzalutamide.

Enzalutamide in Combination With Gemcitabine and Nab-Paclitaxel for the Treatment of Advanced Pancreatic Cancer

A Phase I Trial With Cohort Expansion of Enzalutamide in Combination With Gemcitabine and Nab-Paclitaxel for the Treatment of Advanced Pancreatic Cancer

To determine the maximally tolerated dose (MTD) of enzalutamide in combination with gemcitabine and nab-paclitaxel in advanced pancreatic cancer.

Astellas Pharma Inc

H. Lee Moffitt Cancer Center and Research Institute

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Immune and Endocrine Systems in Chronic Non-cancer Patients Treated With Opioids	NCT02277080	Pain Opioids Immune System Endocrine Syste... Quality of Life		18 Years - 65 Years	Rigshospitalet, Denmark
The Immune and Endocrine Systems in Chronic Non-cancer Patients Treated With Opioids	NCT02277080	Pain Opioids Immune System Endocrine Syste... Quality of Life		18 Years - 65 Years	Rigshospitalet, Denmark
Enzalutamide in Combination With Gemcitabine and Nab-Paclitaxel for the Treatment of Advanced Pancreatic Cancer	NCT02138383	Pancreatic Canc...	Enzalutamide Gemcitabine Nab-paclitaxel	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Enzalutamide in Combination With Gemcitabine and Nab-Paclitaxel for the Treatment of Advanced Pancreatic Cancer	NCT02138383	Pancreatic Canc...	Enzalutamide Gemcitabine Nab-paclitaxel	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for endocrine system