Hormone Function in Men Treated for Pain With Opioids or Placebo

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Nursing Research (NINR) )
ClinicalTrials.gov Identifier:
NCT00737737
First received: August 16, 2008
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Chronic Pain
Osteoarthritis
Drug: MS Contin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Effects of Chronic Musculoskeletal Pain and Opioidergic Versus Placebo Interventions on Neuroendocrine Function in Men

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Is chronic opioid treatment associated with changes in ACTH, cortisol, LH and testosterone secretion? [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Is placebo analgesia associated with a similar hormonal response as elicited by an opioid analgesic? [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: August 2008
Study Completion Date: April 2014
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: MS Contin
    N/A
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 ACTH, cortisol, 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.

  Eligibility

Ages Eligible for Study:   30 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00737737

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Andrew J Mannes, M.D. National Institutes of Health Clinical Center (CC)
  More Information

Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Nursing Research (NINR) )
ClinicalTrials.gov Identifier: NCT00737737     History of Changes
Other Study ID Numbers: 080190, 08-NR-0190
Study First Received: August 16, 2008
Last Updated: April 24, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Analgesia
Chronic Pain
Neuroendocrine Axis
Degenerative Diseases

Additional relevant MeSH terms:
Osteoarthritis
Chronic Pain
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms

ClinicalTrials.gov processed this record on October 01, 2014