Clinical trial NCT00737737
Conditions: Chronic Pain Osteoarthritis
Keywords: Analgesia Chronic Pain Neuroendocrine Axis Degenerative Diseases
Sponsor: National Institute of Nursing Research (NINR)
Start date: 2008-08-01; Completion date: 2014-04-01
Enrollment: 8 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

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.

Arms: arm 1: 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 arm 2: Participants will receive a similar number of placebo tablets which match the study drug with regards to appearance over a period of 4 weeks
Interventions: intervention 1: MS Contin intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents: