Chronic PainPhase 4NCT00737737
Hormone Function in Men Treated for Pain With Opioids or Placebo
A Phase 4 study testing MS Contin in people with Chronic Pain and Osteoarthritis, run by National Institute of Nursing Research (NINR) at 1 site in United States.
Trial summary
This study will examine hormone function in men with osteoarthritis pain and how it is affected by opioid medication (such as Percocet, Vicodin, MS Contin and morphine) versus placebo. Read more about this study
- Who is it for?
- Ages 30 to 65 years, men only
- Conditions the study is for
- Chronic Pain, Osteoarthritis
- What is being tested?
- MS Contin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2008to Apr 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 30 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Impaired pulmonary, renal, hepatic, cardiovascular or endocrine-metabolic function or major coexisting medical condition such as cancer, Cushing s disease, and diabetes which may make participation unsafe or interfere with hormone measurements
- Prostatic disease or hypertrophy which would make subjects prone to urinary retention or require medication that would interfere with study hormone measurements
- Sexual dysfunction including lack of libido, impotence or erectile abnormalities for safety reasons as these symptoms may be worsened by morphine
- Rheumatoid arthritis other types of inflammatory arthritis
- Use of systemic corticosteroids in the two months before study entry which might interfere with study hormone measurements
- Present or past history of alcohol dependence which might predispose subjects to problems with opioid dependence based on 2 or more positive responses to the CAGE questionnaire (the latter group will be referred to psychiatry for further evaluation and excluded from study if found to fulfill psychiatric criteria for alcohol dependence or abuse)
Show all 16Show fewer
- Current usage of any recreational or unauthorized prescription drugs because this may indicate abuse potential based on positive urine drug test at study screening visit
- History of opioid abuse at any time in the past based on patient report or a urine drug screen positive for opioids
- Major depression based on a score of greater than or equal to 20 on the Beck Depression Inventory at screening, present history of major depression or treatment for major depression because these may effect endocrine function
- Hct < 35; anemia or bleeding disorder because subjects will undergo serial blood sampling to assess hormone function
- Allergy or inability to tolerate to morphine
- Current or past fibromyalgia according to Wolfe criteria (1990)
- Present or past history of sleep apnea because of increased risk of respiratory depression with morphine
- Body mass index (BMI) > 30kg/m(2) and BMI < 20kg/m(2)
- Local steroid injections during the study because weight has significant effects on hormone levels
- Addition of or changes to complementary or alternative treatments during the study
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Effects of Chronic Musculoskeletal Pain and Opioidergic Versus Placebo Interventions on Neuroendocrine Function in Men
This study will examine hormone function in men with osteoarthritis pain and how it is affected by opioid medication (such as Percocet, Vicodin, MS Contin and morphine) versus placebo.
Men between 30 and 65 years of age who have had moderate to severe osteoarthritis joint pain at least 5 days a week over the past 3 months may be eligible for this study. Candidates are screened with a physical examination, x-rays, laboratory and other tests, and questionnaires about pain, mood and medical health. They are given a pain diary to complete for 2 weeks.
Read more
Participants are admitted to the hospital for two 12 hour overnight stays, during each of which they provide a 24-hour urine collection and have a small blood sample drawn every 20 minutes for 12 hours (from 8:00 p.m. to 8:00 a.m.) through a catheter that remains in place in a vein. Blood pressure and pulse are monitored during this time. After the catheter is removed, subjects complete questionnaires about their pain, mood and activity.
For the several weeks between the two hospitalizations, subjects take either an opioid medication or placebo, or standard medication such as motrin and naprosyn, according to random assignment to one of the three groups. All participants will be allowed to take anti-inflammatory medications and acetaminophen during this time as needed, but no other pain medications or treatments. They are monitored two or three times a week by telephone and complete a pain diary.
After the second hospitalization, subjects are tapered off the study medication. After 2 to 4 weeks of stopping medication, they return for a final outpatient visit to review pain or other medical problems and to have blood drawn.
Read the detailed description
Use of opioid medicines for relief of chronic pain is increasing substantially but opioidergic medications and chronic pain have been both shown to perturb neuroendocrine function. The objective of this protocol is:
To determine whether long term opioid usage in men with chronic pain due to osteoarthritis results in abnormalities of Adrenocorticotropic Hormone (ACTH), cortisol, Luteinizing Hormone (LH) and testosterone secretion.
This protocol is a revised continuation of a two phase protocol with the same name which was initiated at NCCAM in 2004. In the first phase of this study 12 opioid na(SqrRoot) ve men with chronic OA pain were compared to12 healthy men by means of 12 hour overnight frequent blood sampling for measurement of baseline ACTH, cortisol, LH and testosterone. The results of phase 1 suggest that chronic osteoarthritis pain does not affect ACTH, cortisol, LH and testosterone secretion in middle aged men as compared to matched controls. In the second phase the NCCAM protocol intended to evaluate the effect of long term opioid usage AND the placebo effect if any- on the same hormones in men with chronic OA pain. Therefore the NCCAM study had a three arm design comparing MS Contin to placebo and standard treatment. When the protocol was being revised under NINR, review of the placebo literature suggested that placebo effect becomes negligible with time and therefore a two arm design was chosen comparing morphine to placebo. Baseline overnight blood hormone sampling, doses of medication, escalation and tapering schedules will be the same as in phase II of the NCCAM protocol.
Because of design changes the sample size was however recalculated to be a total of 30 opioid na(SqrRoot) ve patients with chronic OA pain. Fourteen patients, previously recruited under NCCAM, had been randomized to either morphine or placebo and finished the study. Therefore 16 additional patients need to complete the study. Taking into consideration a 25% drop out rate therefore a total of 20 patients need to be recruited. After undergoing overnight baseline hormone sampling all patients will be randomized to one of two treatment groups: MS Contin (15-90 mg), or placebo Doses of placebo and MS Contin will be escalated over 4-8 weeks in a similar fashion followed by a two-week maintenance period. At that point patients will return for repeat 12 hour frequent sampling of the same hormones as at baseline. They will then be tapered off of study medications over a period of 2-4 weeks as outpatients. Subjects will then return to clinic for a final visit and, AM blood will be obtained for ACTH, cortisol, LH, and testosterone.
The primary endpoints of this study are measures of ACTH, cortisol, LH, and testosterone secretion, whereas secondary endpoints are neurobehavioral indices such as pain symptomatology on a 0-10 (Likert) scale, the Oswestry Disability Index, Multidimensional Pain Inventory, and the Beck Depression Inventory. It is anticipated that the results of the second phase of this study will provide novel information regarding the effects of treatment with opioids on selected neuroendocrine functions in men.
- Conditions
- Chronic Pain, Osteoarthritis
- Being tested
- MS Contin, Placebo
- Keywords
- Analgesia, Chronic Pain, Neuroendocrine Axis, Degenerative Diseases
- Medical subject headings
- Chronic Pain, Osteoarthritis, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MS ContinDrug
Also called oxycodone, morphine
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Opioid | Experimental | Participants will receive MS Contin over a 4 week period starting at 15 mg bid. Doses will titrated upwards as tolerated by increments of 15-30 mg to a highest attained dose or a maximum dose of 90 mg Receives: Drug: MS Contin |
| Placebo | Experimental | Participants will receive a similar number of placebo tablets which match the study drug with regards to appearance over a period of 4 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Is Chronic Opioid Treatment Associated With Changes in Adrenocorticotropic Hormone (ACTH), Cortisol, Luteinizing Hormone (LH) and Testosterone Secretion?
Measured: 4 weeks
Secondary outcomes (1)
Is Placebo Analgesia Associated With a Similar Hormonal Response as Elicited by an Opioid Analgesic?
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2008 (estimated)
- Study startAug 2008
- Primary completionSep 2013
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Nursing Research (NINR)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Andrew J Mannes, M.D., Principal investigator, National Institutes of Health Clinical Center (CC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00737737
- Sponsor's protocol ID
- 080190
- Other IDs
- 08-NR-0190
- Status last verified
- Apr 2015
- First submitted
- 16 Aug 2008
- Last updated
- 29 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Joranson DE, Ryan KM, Gilson AM, Dahl JL. Trends in medical use and abuse of opioid analgesics. JAMA. 2000 Apr 5;283(13):1710-4. doi: 10.1001/jama.283.13.1710.
PubMed 10755497Bolelli G, Lafisca S, Flamigni C, Lodi S, Franceschetti F, Filicori M, Mosca R. Heroin addiction: relationship between the plasma levels of testosterone, dihydrotestosterone, androstenedione, LH, FSH, and the plasma concentration of heroin. Toxicology. 1979 Dec;15(1):19-29. doi: 10.1016/0300-483x(79)90016-7.
PubMed 120622Celani MF, Carani C, Montanini V, Baraghini GF, Zini D, Simoni M, Ferretti C, Marrama P. Further studies on the effects of heroin addiction on the hypothalamic-pituitary-gonadal function in man. Pharmacol Res Commun. 1984 Dec;16(12):1193-203. doi: 10.1016/s0031-6989(84)80084-3.
PubMed 6522443
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Chronic Musculoskeletal Pain and Opioidergic Versus Placebo Interventions on Neuroendocrine Function in Men
- ClinicalTrials.gov ID
- NCT00737737
- Acronym / sponsor ID
- 080190
- Conditions
- Chronic Pain, Osteoarthritis
- Keywords
- Analgesia, Chronic Pain, Neuroendocrine Axis, Degenerative Diseases
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- National Institute of Nursing Research (NINR)US National Institutes of Health
- Study start
- Aug 2008
- Primary completion
- Sep 2013 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 20 Aug 2008 (estimated)
- Results
- Posted 29 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine hormone function in men with osteoarthritis pain and how it is affected by opioid medication (such as Percocet, Vicodin, MS Contin and morphine) versus placebo.
Men between 30 and 65 years of age who have had moderate to severe osteoarthritis joint pain at least 5 days a week over the past 3 months may be eligible for this study. Candidates are screened with a physical examination, x-rays, laboratory and other tests, and questionnaires about pain, mood and medical health. They are given a pain diary to complete for 2 weeks.
Participants are admitted to the hospital for two 12 hour overnight stays, during each of which they provide a 24-hour urine collection and have a small blood sample drawn every 20 minutes for 12 hours (from 8:00 p.m. to 8:00 a.m.) through a catheter that remains in place in a vein. Blood pressure and pulse are monitored during this time. After the catheter is removed, subjects complete questionnaires about their pain, mood and activity.
For the several weeks between the two hospitalizations, subjects take either an opioid medication or placebo, or standard medication such as motrin and naprosyn, according to random assignment to one of the three groups. All participants will be allowed to take anti-inflammatory medications and acetaminophen during this time as needed, but no other pain medications or treatments. They are monitored two or three times a week by telephone and complete a pain diary.
After the second hospitalization, subjects are tapered off the study medication. After 2 to 4 weeks of stopping medication, they return for a final outpatient visit to review pain or other medical problems and to have blood drawn.
Detailed description
Use of opioid medicines for relief of chronic pain is increasing substantially but opioidergic medications and chronic pain have been both shown to perturb neuroendocrine function. The objective of this protocol is:
To determine whether long term opioid usage in men with chronic pain due to osteoarthritis results in abnormalities of Adrenocorticotropic Hormone (ACTH), cortisol, Luteinizing Hormone (LH) and testosterone secretion.
This protocol is a revised continuation of a two phase protocol with the same name which was initiated at NCCAM in 2004. In the first phase of this study 12 opioid na(SqrRoot) ve men with chronic OA pain were compared to12 healthy men by means of 12 hour overnight frequent blood sampling for measurement of baseline ACTH, cortisol, LH and testosterone. The results of phase 1 suggest that chronic osteoarthritis pain does not affect ACTH, cortisol, LH and testosterone secretion in middle aged men as compared to matched controls. In the second phase the NCCAM protocol intended to evaluate the effect of long term opioid usage AND the placebo effect if any- on the same hormones in men with chronic OA pain. Therefore the NCCAM study had a three arm design comparing MS Contin to placebo and standard treatment. When the protocol was being revised under NINR, review of the placebo literature suggested that placebo effect becomes negligible with time and therefore a two arm design was chosen comparing morphine to placebo. Baseline overnight blood hormone sampling, doses of medication, escalation and tapering schedules will be the same as in phase II of the NCCAM protocol.
Because of design changes the sample size was however recalculated to be a total of 30 opioid na(SqrRoot) ve patients with chronic OA pain. Fourteen patients, previously recruited under NCCAM, had been randomized to either morphine or placebo and finished the study. Therefore 16 additional patients need to complete the study. Taking into consideration a 25% drop out rate therefore a total of 20 patients need to be recruited. After undergoing overnight baseline hormone sampling all patients will be randomized to one of two treatment groups: MS Contin (15-90 mg), or placebo Doses of placebo and MS Contin will be escalated over 4-8 weeks in a similar fashion followed by a two-week maintenance period. At that point patients will return for repeat 12 hour frequent sampling of the same hormones as at baseline. They will then be tapered off of study medications over a period of 2-4 weeks as outpatients. Subjects will then return to clinic for a final visit and, AM blood will be obtained for ACTH, cortisol, LH, and testosterone.
The primary endpoints of this study are measures of ACTH, cortisol, LH, and testosterone secretion, whereas secondary endpoints are neurobehavioral indices such as pain symptomatology on a 0-10 (Likert) scale, the Oswestry Disability Index, Multidimensional Pain Inventory, and the Beck Depression Inventory. It is anticipated that the results of the second phase of this study will provide novel information regarding the effects of treatment with opioids on selected neuroendocrine functions in men.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Opioid | Experimental | Drug: MS ContinParticipants will receive MS Contin over a 4 week period starting at 15 mg bid. Doses will titrated upwards as tolerated by increments of 15-30 mg to a highest attained dose or a maximum dose of 90 mg |
| Placebo | Experimental | Drug: PlaceboParticipants will receive a similar number of placebo tablets which match the study drug with regards to appearance over a period of 4 weeks |
Who may qualify
- Ages
- 30 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (16 listed)
- Impaired pulmonary, renal, hepatic, cardiovascular or endocrine-metabolic function or major coexisting medical condition such as cancer, Cushing s disease, and diabetes which may make participation unsafe or interfere with hormone measurements
- Prostatic disease or hypertrophy which would make subjects prone to urinary retention or require medication that would interfere with study hormone measurements
- Sexual dysfunction including lack of libido, impotence or erectile abnormalities for safety reasons as these symptoms may be worsened by morphine
- Rheumatoid arthritis other types of inflammatory arthritis
- Use of systemic corticosteroids in the two months before study entry which might interfere with study hormone measurements
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MS ContinAlso: oxycodone, morphine | Drug | Opioid |
| Placebo | Drug | Placebo |
Primary outcome
Is Chronic Opioid Treatment Associated With Changes in Adrenocorticotropic Hormone (ACTH), Cortisol, Luteinizing Hormone (LH) and Testosterone Secretion?
Time frame: 4 weeks
1 secondary outcome
Is Placebo Analgesia Associated With a Similar Hormonal Response as Elicited by an Opioid Analgesic?
Time frame: 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10755497Joranson DE, Ryan KM, Gilson AM, Dahl JL. Trends in medical use and abuse of opioid analgesics. JAMA. 2000 Apr 5;283(13):1710-4. doi: 10.1001/jama.283.13.1710.
- Background: PubMed 120622Bolelli G, Lafisca S, Flamigni C, Lodi S, Franceschetti F, Filicori M, Mosca R. Heroin addiction: relationship between the plasma levels of testosterone, dihydrotestosterone, androstenedione, LH, FSH, and the plasma concentration of heroin. Toxicology. 1979 Dec;15(1):19-29. doi: 10.1016/0300-483x(79)90016-7.
- Background: PubMed 6522443Celani MF, Carani C, Montanini V, Baraghini GF, Zini D, Simoni M, Ferretti C, Marrama P. Further studies on the effects of heroin addiction on the hypothalamic-pituitary-gonadal function in man. Pharmacol Res Commun. 1984 Dec;16(12):1193-203. doi: 10.1016/s0031-6989(84)80084-3.
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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.
Andrew J Mannes, M.D. principal investigator
National Institutes of Health Clinical Center (CC)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing MS Contin in people with Chronic Pain and Osteoarthritis, run by National Institute of Nursing Research (NINR) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 16 exclusion criteria. 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 29 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Is Chronic Opioid Treatment Associated With Changes in Adrenocorticotropic Hormone (ACTH), Cortisol, Luteinizing Hormone (LH) and Testosterone Secretion? (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00737737, which also lists 3 linked publications.
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 29 Apr 2015.