Hormone Function in Men Treated for Pain With Opioids or Placebo

NCT00737737 | Completed Phase 4 Results

• 2 other identifiers: 08019008-NR-0190
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Pain; Osteoarthritis

Keywords

Analgesia; Chronic Pain; Neuroendocrine Axis; Degenerative Diseases

Outcome Measures

Primary Outcomes (1)

• Is Chronic Opioid Treatment Associated With Changes in Adrenocorticotropic Hormone (ACTH), Cortisol, Luteinizing Hormone (LH) and Testosterone Secretion?

  4 weeks

Secondary Outcomes (1)

• Is Placebo Analgesia Associated With a Similar Hormonal Response as Elicited by an Opioid Analgesic?

  4 weeks

Study Arms (2)

Opioid

EXPERIMENTAL

Participants will receive MS Contin over a 4 week period starting at 15 mg bid. Doses will titrated upwards as tolerated by increments of 15-30 mg to a highest attained dose or a maximum dose of 90 mg

Drug: MS Contin

Placebo

EXPERIMENTAL

Participants will receive a similar number of placebo tablets which match the study drug with regards to appearance over a period of 4 weeks

Drug: Placebo

Interventions

MS Contin DRUG

Also known as: oxycodone, morphine

Opioid

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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 alcohol during the study because alcohol may exacerbate the sedative effects of morphine
• Willingness to refrain from using muscle relaxers, antiepileptic medications and antidepressants within 6 weeks of starting study procedures
• 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

You may not qualify if:

• 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 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 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)
• 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
• History of opioid abuse at any time in the past based on patient report or a urine drug screen positive for opioids
• 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
• Hct \< 35; anemia or bleeding disorder because subjects will undergo serial blood sampling to assess hormone function
• Allergy or inability to tolerate 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) \> 30kg/m(2) and BMI \< 20kg/m(2)
• Local steroid injections during the study because weight has significant effects on hormone levels

Sponsors & Collaborators

• National Institute of Nursing Research (NINR): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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. doi: 10.1001/jama.283.13.1710.

  PMID: 10755497 BACKGROUND

• 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. doi: 10.1016/0300-483x(79)90016-7.

  PMID: 120622 BACKGROUND

• 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. doi: 10.1016/s0031-6989(84)80084-3.

  PMID: 6522443 BACKGROUND

MeSH Terms

Conditions

Chronic Pain; Osteoarthritis; Agnosia

Interventions

Morphine; Oxycodone

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Codeine

Results Point of Contact

• Title: Andrew Mannes, M.D.
• Organization: National Institutes of Health Clinical Center

Andrew.Mannes@nih.gov

301-594-3427

Study Officials

• Andrew J Mannes, M.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2008
• First Posted: August 20, 2008
• Study Start: August 1, 2008
• Primary Completion: September 1, 2013
• Study Completion: April 1, 2014
• Last Updated: April 29, 2015
• Results First Posted: April 29, 2015

Record last verified: 2015-04

Locations

US (1)