PainNCT02277080
The Immune and Endocrine Systems in Chronic Non-cancer Patients Treated With Opioids
An observational study of Pain and Opioids, run by Copenhagen University Hospital, Rigshospitalet.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Pain, Opioids, Immune System
- How many people
- 82 participants
- Where
- No sites listed yet
- Study dates
- Sep 2014to 28 Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Pain patients at Multidisciplinary Pain Centre at Rigshospitalet, Denmark
CRITERIA FOR INCLUSION IN THE OPIOID GROUP
- Age >18 yrs and <65 yrs
- Chronic non-cancer pain (>6 months' duration)
- At least six years of schooling
- Fluent in spoken and written Danish
- On opioid treatment (>30 mg of morphine equivalents pr. day) for at least one month
CRITERIA FOR INCLUSION IN THE CONTROL GROUP
- Age >18 yrs and <65 yrs
- Chronic non-cancer pain (>6 months' duration)
- At least six years of schooling
- Fluent in spoken and written Danish (no need for translator)
- No analgesic treatment for the last month
CRITERIA FOR EXCLUSION
- Treatment with glucocorticoid or sex hormones within the previous 6 months or on-going therapy with drugs known to interfere with endocrine function
- Treatment with adjuvant analgesics (anticonvulsants, antidepressants and others), NSAIDs/paracetamol, benzodiazepines and hypnotics (sleeping pills can be discontinued 3 days before testing) the last month
- Known endocrine disease including insulin treated diabetes mellitus
- Previously diagnosed dementia or encephalopathy
- Brain trauma necessitating hospitalization within last 6 months
- Previously diagnosed liver disease
- Renal insufficiency (serum creatinine concentration >140 µmol/l)
- Pregnancy
About this study
Official title: The Immune and Endocrine Systems in Chronic Non-cancer Patients Treated With Opioids: Effects on Cognition, Pain and Quality of Life
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.
Read the detailed description
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:
- 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.
- 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.
- Conditions
- Pain, Opioids, Immune System, Endocrine System, Quality of Life
- Keywords
- Pain, opioids, immune system, endocrine system, quality of life
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Opioid group | These patients should have been treated only with one opioid (morphine, oxycodone, fentanyl, methadone, hydromorphone, tapentadol or tramadol) for more than one month | |
| Control group | Chronic non-cancer pain patients not treated with analgesics |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose and time dependent effects
Differences on the mean results of endocrine and immunologic blood tests between patients and controls, considering dose and time dependent effects.
Measured: Up to 2.5 years
Secondary outcomes (1)
Function of the immune and endocrine systems
Differences on the mean scores of the cognitive tests, pain intensity and quality of life between patients and controls.
Measured: Up to 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2014 (estimated)
- Study startSep 2014
- Primary completionJun 2021
- Study completion28 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Per Sjogren, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Per Sjøgren, Proff., Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02277080
- Sponsor's protocol ID
- H-1-2014-063
- Status last verified
- Mar 2023
- First submitted
- 22 Oct 2014
- Last updated
- 20 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Immune and Endocrine Systems in Chronic Non-cancer Patients Treated With Opioids: Effects on Cognition, Pain and Quality of Life
- ClinicalTrials.gov ID
- NCT02277080
- Acronym / sponsor ID
- H-1-2014-063
- Conditions
- Pain, Opioids, Immune System, Endocrine System, Quality of Life
- Keywords
- Pain, opioids, immune system, endocrine system, quality of life
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Study start
- Sep 2014 (actual)
- Primary completion
- Jun 2021 (actual)
- Study completion
- 28 Dec 2022 (actual)
- First posted
- 28 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- 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.
- 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.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Opioid group | – | –These patients should have been treated only with one opioid (morphine, oxycodone, fentanyl, methadone, hydromorphone, tapentadol or tramadol) for more than one month |
| Control group | – | –Chronic non-cancer pain patients not treated with analgesics |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Pain patients at Multidisciplinary Pain Centre at Rigshospitalet, Denmark
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Dose and time dependent effects
Time frame: Up to 2.5 years
Differences on the mean results of endocrine and immunologic blood tests between patients and controls, considering dose and time dependent effects.
1 secondary outcome
Function of the immune and endocrine systems
Time frame: Up to 2.5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Per Sjøgren, Proff. principal investigator
Copenhagen University Hospital, Rigshospitalet
Questions about this trial
What is this clinical trial studying?
An observational study of Pain and Opioids, run by Copenhagen University Hospital, Rigshospitalet.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose and time dependent effects (time frame: Up to 2.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2023.