Effects of Osteoarthritis Pain, Morphine, and Placebo on Neuroendocrine Function in Men

NCT00088296 | Completed Phase 2

• 2 other identifiers: 04023904-AT-0239
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the effects of morphine on leuteinizing hormone, testosterone, adrenocorticotropic hormone and cortisol in men. The use of long-term opioids, such as morphine, to treat patients with pain is increasing, despite a dearth of information about their effects on hormones. The study will also look at the effect of chronic pain on these hormone levels and the effect of placebo on pain. Men between 30 and 65 years of age who have had moderate to severe chronic pain due to osteoarthritis for at least 3 months and healthy, pain-free men in the same age range may be eligible for this study. Patients taking an opioid-based medication such as percocet, vicodin, or morphine for pain relief, as well as patients who are not taking opioids, may participate. Candidates are screened with a medical history, physical examination, blood tests, including a blood test to look for possible "pain genes," electrocardiogram, x-ray, and questionnaires that assess the impact of pain on functional level and psychological well being. This is a four-part study. Healthy volunteers and patients who are taking opioids for their arthritis pain end their participation after Part I; those who are not taking opioids continue with Parts II, III, and IV, as follows: Part I: Participants are admitted to the NIH Clinical Center at 4 p.m. for an overnight stay. At 6 p.m. a catheter (plastic tube) is placed in a vein in the forearm and remains in place throughout the night. Blood samples of 3 cc's each (less than a teaspoon) are collected through the catheter every 20 minutes for 12 hours, from 8 p.m. until 8 a.m. Participants also collect their urine starting from 8 a.m. on the morning of hospital admission and continue the collection throughout their 24-hour hospital stay. Patients are discharged at the completion of the blood sampling. Part II: Patients are randomly assigned to take morphine (MS Contin), placebo, or standard treatment, which consists of anti-inflammatory medications and acetaminophen as needed, but no opioids. (Patients in groups I and II are also permitted to take anti-inflammatory drugs and acetominophen, in addition to their study medication.) Patients are monitored for drug side effects by phone twice a week, and medication doses are adjusted as needed. The morphine dose is gradually increased over a 4-week period if no side effects develop. After 2 weeks on the highest dose of morphine, hormone blood levels are measured and patients complete questionnaires. Patients are readmitted to the hospital for a repeat blood sampling and blood collection as in Part I. Patients on morphine and placebo are then gradually tapered off drug over 12 days and remain drug-free for 2 days before starting Part III. Part III: All patients are given morphine in this part of the study and are monitored for drug side effects by phone twice a week, with doses adjusted as needed. The morphine is gradually increased over a 6-week period if no side effects develop and is maintained at the highest dose for another 8 weeks. Hormone levels are measured and the blood and urine studies and questionnaires are repeated. Patients interested in continuing long-term treatment with MC Contin are referred back to their physicians with recommendations to that effect. Part IV: Patients are followed by phone for 6 months, at which time they return to the Clinical Center for hormone level measurements, repeat blood and urine tests, and questionnaires.

Conditions

Osteoarthritis

Keywords

Osteoarthritis; MS Contin; Placebo; Cortisol; Testosterone; Degenerative Joint Disease; OA; Arthritis; Joint Pain; Arthritic Pain; Opioid

Interventions

Blood Draw PROCEDURE

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical evidence of chronic OA by history and examination in a major joint or the spine.
• Pain level of 4/10 or greater on a scale of 0 to 10
• Pain for a duration of 3 months or longer present at least 5 out of 7 days a week
• Radiographic evidence of moderate to severe OA in the involved joint based on the Kellgren and Lawrence scoring scale.
• Age between 30-65 at study entry
• Men of all ethnicities
• Ability to understand the study measures and mentally capable of giving consent to participate in the study (based on an 8th grade education level)
• Willingness to refrain from taking opioids other than as dictated by the study design

You may not qualify if:

• Impaired pulmonary, renal, hepatic, cardiovascular or endocrine-metabolic function; major coexisting medical condition such as cancer, chronic obstructive pulmonary disease and severe hepatic and renal dysfunction
• Primary or secondary endocrine disease such as diabetes or Cushing's syndrome
• Prostatic disease requiring usage of urological medications
• Presence of sexual dysfunction defined as lack of libido, impotence or erectile abnormalities.
• Current symptoms of coronary artery disease
• Presence of RA, or other types of inflammatory arthritis
• Use of systemic corticosteroids in the two months before screening and study entry
• Alcohol abuse up to a year prior to study enrollment
• Usage of any recreational drugs
• History of narcotic abuse at any time in the past
• Major depression whether successfully or unsuccessfully treated or diagnosed at the time of study screening based on a score of greater than or equal to 20 on the Beck Depression Inventory
• Hct less than 35; anemia or bleeding disorder
• Allergy to morphine
• Current or past history of fibromyalgia as described by Wolfe F et al., (1990) (a minimum of 12 out of 19 points of tenderness must be present to satisfy criteria for fibromyalgia)
• Cognitive impairment such that the individual is unable to give informed consent, complete study data collection tools or required study visits

Sponsors & Collaborators

• National Center for Complementary and Integrative Health (NCCIH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• 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

Osteoarthritis; Joint Diseases; Arthritis; Arthralgia

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Rheumatic Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: July 23, 2004
• First Posted: July 26, 2004
• Study Start: July 13, 2004
• Study Completion: October 18, 2007
• Last Updated: July 2, 2017

Record last verified: 2007-10-18

Locations

US (1)