Hormone Function in Men Treated for Pain With Opioids or Placebo
Condition: Chronic Pain; Osteoarthritis
MeSH terms: Chronic Pain
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): MS Contin; Placebo
Intervention type(s): Drug; Drug
Other intervention name(s): oxycodone, morphine
Intervention MeSH terms: Morphine; Oxycodone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Analgesia; Chronic Pain; Neuroendocrine Axis; Degenerative Diseases