Hormone Function in Men Treated for Pain With Opioids or Placebo

Condition(s) targeted: Chronic Pain; Osteoarthritis

Intervention: MS Contin (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: National Institute of Nursing Research (NINR)

Overall contact:
Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov

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.

Official title: Effects of Chronic Musculoskeletal Pain and Opioidergic Versus Placebo Interventions on Neuroendocrine Function in Men

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Safety Study

Primary outcome: Is chronic opioid treatment associated with changes in ACTH, cortisol, LH and testosterone secretion?

Secondary outcome: Is placebo analgesia associated with a similar hormonal response as elicited by an opioid analgesic?

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 objectives of this protocol are:

1. To determine whether long term opioid usage in men with chronic pain due to osteoarthritis results in abnormalities of ACTH, cortisol, LH and testosterone secretion.

2. To evaluate whether placebo analgesia results in a similar hormonal response as an opioid analgesic.

3. To evaluate the effects of chronic pain per se on ACTH, cortisol, LH and testosterone secretion.

To address these questions, a protocol with the same name was initiated at NCCAM in 2004. In the first phase of this study 12 opioid naive 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 phase 2, 36 opioid naive patients with chronic OA pain, all of whom will have undergone overnight baseline hormone sampling are randomized to one of three treatment groups: MS Contin (15-90 mg), placebo and standard treatment. Standard treatment includes nonsteroidal anti-inflammatory medications and Tylenol only. Doses of placebo and MS Contin are escalated over 4-8 weeks in a similar fashion followed by a two-week maintenance period. At that point patients return for repeat 12 hour frequent sampling of the same hormones as at baseline. They are then tapered off of study medications over a period of 2-4 weeks as outpatients. Subjects then return to clinic for a final visit and, AM blood will be obtained for ACTH, cortisol, LH, and testosterone. Twenty four subjects have already been recruited in this phase of the study (including the 12 opioid na ve men whose baseline endocrine functions were measured in phase 1.

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 and placebo effect on selected neuroendocrine functions in men.

Minimum age: 30 Years. Maximum age: 65 Years. Gender(s): Male.

Criteria:

- INCLUSION CRITERIA:

- Clinical evidence of chronic OA by history, examination and radiological examination

- Pain level of 4/10 or greater on a scale of 0 to 10 over a 2-week screening period

- Pain for a duration of 3 months or longer present at least 5 out of 7 days a week by

history

- Radiographic evidence of moderate to severe OA in at least one joint selected for

study, based on the Kellgren and Lawrence scoring scale

- 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.

- Men of all ethnicities

- Ability to provide his own consent and to cooperate with study procedures

- Willingness to refrain from drinking more than one glass of wine or the equivalent

amount of alcohol during the study because alcohol may exacerbate the sedative effects of morphine

EXCLUSION CRITERIA:

- 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 or 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

- Usage of any recreational drugs because this may indicate abuse potential; positive

urine drug test at study screening visit

- History of opioid abuse at any time in the past

- Major depression based on a score of greater than or equal to 20 on the Beck

Depression Inventory at screening because this may affect endocrine function

- Hct less than 35; anemia or bleeding disorder because subjects will undergo serial

blood sampling to assess hormone function

- Allergy 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) greater than 30kg/m(2) and BMI less than 20kg/m(2) because

weight has significant effects on hormone levels

- Local steroid injections during the study

Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov

National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States; Recruiting

NIH Clinical Center Detailed Web Page

Related 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.

Bolelli 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.

Celani 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.

Starting date: August 2008
Ending date: December 2010
Last updated: October 2, 2009