Hormone Function in Men Treated for Pain With Opioids or Placebo
Condition: Chronic Pain; Osteoarthritis
MeSH terms: Chronic Pain
Intervention: MS Contin; Placebo
Intervention MeSH terms: Morphine; Oxycodone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 8.0
Sex: Male
Minimum age: 30 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Analgesia; Chronic Pain; Neuroendocrine Axis; Degenerative Diseases

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.
    

Eligibility criteria:

        -INCLUSION CRITERIA:

          1. Clinical evidence of chronic OA by history, examination and radiological examination

               -  a. Pain level of 4/10 or greater on a scale of 0 to 10 over a 2 week screening
                  period

               -  b. Pain for a duration of 3 months or longer present at least 5 out of 7 days a
                  week by history

               -  c. Radiographic evidence of moderate to severe OA in at least one joint selected
                  for study based on the Kellgren and Lawrence scoring scale (Appendix I:Table 2)

          2. Age between 30-65 at study entry. This age range was chosen as osteoarthritis is rare
             in people younger than 30 and to minimize the effect of the neuroendocrine changes
             associated with aging on study outcome measures.

          3. Men of all ethnicities

          4. Ability to provide his own consent and to cooperate with study procedures

          5. Willingness to refrain from drinking alcohol during the study because alcohol may
             exacerbate the sedative effects of morphine

          6. Willingness to refrain from using muscle relaxers, antiepileptic medications and
             antidepressants within 6 weeks of starting study procedures

          7. Willingness not to be on opioids other than prescribed by the study for the duration
             of the study and willingness to come off of opioids six weeks prior to starting study
             procedures

        EXCLUSION CRITERIA:

          1. 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

          2. Prostatic disease or hypertrophy which would make subjects prone to urinary retention
             or require medication that would interfere with study hormone measurements

          3. Sexual dysfunction including lack of libido, impotence or erectile abnormalities for
             safety reasons as these symptoms may be worsened by morphine

          4. Rheumatoid arthritis other types of inflammatory arthritis

          5. Use of systemic corticosteroids in the two months before study entry which might
             interfere with study hormone measurements

          6. 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)

          7. 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

          8. History of opioid abuse at any time in the past based on patient report or a urine
             drug screen positive for opioids

          9. 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

         10. Hct < 35; anemia or bleeding disorder because subjects will undergo serial blood
             sampling to assess hormone function

         11. Allergy or inability to tolerate to morphine

         12. Current or past fibromyalgia according to Wolfe criteria (1990)

         13. Present or past history of sleep apnea because of increased risk of respiratory
             depression with morphine

         14. Body mass index (BMI) > 30kg/m(2) and BMI < 20kg/m(2)

         15. Local steroid injections during the study because weight has significant effects on
             hormone levels

         16. Addition of or changes to complementary or alternative treatments during the study