Hormone Function in Men Treated for Pain With Opioids or Placebo - Full Text View

Sponsor:	National Institute of Nursing Research (NINR)
Collaborator:	National Institute of Mental Health (NIMH)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00737737

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 IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Control: Placebo Control 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:

MedlinePlus related topics: Osteoarthritis

U.S. FDA Resources

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 ]

Estimated Enrollment:	18
Study Start Date:	August 2008
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Intervention Details:

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 objectives of this protocol are:

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

Eligibility

Ages Eligible for Study:	30 Years to 65 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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

Contacts

Contact: Patient Recruitment and Public Liaison Office	(800) 411-1222	prpl@mail.cc.nih.gov
Contact: TTY	1-866-411-1010

Locations

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

Sponsors and Collaborators

National Institute of Nursing Research (NINR)

National Institute of Mental Health (NIMH)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

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.

Responsible Party:	National Institutes of Health ( Raymond A. Dionne Jr., D.D.S./National Institutes of Nursing Research )
Study ID Numbers:	080190, 08-NR-0190
Study First Received:	August 16, 2008
Last Updated:	November 25, 2009
ClinicalTrials.gov Identifier:	NCT00737737 History of Changes
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:

Morphine
Osteoarthritis
Joint Diseases
Physiological Effects of Drugs
Central Nervous System Depressants
Narcotics
Rheumatic Diseases
Pharmacologic Actions

Musculoskeletal Diseases
Sensory System Agents
Therapeutic Uses
Arthritis
Analgesics
Peripheral Nervous System Agents
Central Nervous System Agents
Analgesics, Opioid

ClinicalTrials.gov processed this record on March 18, 2010