Effects of Osteoarthritis Pain, Morphine, and Placebo on Neuroendocrine Function in Men
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00088296|
Recruitment Status : Completed
First Posted : July 26, 2004
Last Update Posted : July 2, 2017
|First Submitted Date ICMJE||July 23, 2004|
|First Posted Date ICMJE||July 26, 2004|
|Last Update Posted Date||July 2, 2017|
|Study Start Date ICMJE||July 13, 2004|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00088296 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Effects of Osteoarthritis Pain, Morphine, and Placebo on Neuroendocrine Function in Men|
|Official Title ICMJE||Effects of Osteoarthritis Pain, Morphine and Placebo on Neuro-Endocrine Function in Men|
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.
Several studies suggest that acceptance and use of opioid medicines for relief of chronic pain are increasing substantially, and that opiodergic medications and chronic pain each perturb neuroendocrine functions, especially those of the hypothalamic pituitary, adrenal, and gonadal axes. The objectives of the proposed protocol, entitled "Effects of Chronic Musculoskeletal Pain and Opioidergic versus Placebo Interventions on Neuro-endocrine Function in Men," are three fold:
To address these questions, we propose a 4-part study. In part I, 12 healthy men will be compared with 12 men with chronic osteoarthritis (OA) pain on long term opioids and 12 narcotic naive men with chronic OA pain by means of 12 hour overnight frequent blood sampling for measurement of cortisol, ACTH, LH and testosterone.
In part II, 36 narcotic naive patients with chronic OA, pain, all of whom will have undergone overnight hormone sampling in Part I, will be randomized to one of three treatment groups: MS Contin (15-90 mg), placebo and "standard treatment."
Doses of placebo and MS Contin will be escalated over 4 weeks in a similar fashion with two-week maintenance and 2 week taper. At the end of maintenance at 6 weeks, all patients will return for repeat 12 hour frequent sampling of the same hormones as in Part I. At the end of part II, patients will be invited to go on to an open label treatment period with MS Contin (15-120 mg) in part III of the study, which will consist of 6-week dose escalation and 8 weeks maintenance. At that point patients will be referred back to their physicians with recommendations for continued treatment with MS Contin, if patients are interested in this option.
Patients will be followed by phone for 6 months. At that point they will be asked to return to clinic for part IV, an outpatient AM sample of testosterone, LH, ACTH and cortisol. The primary endpoints of this study will be measures of LH, testosterone, ACTH, and cortisol secretion, whereas the secondary endpoints will be neurobehavioral indices such as pain and bothersomeness on visual analog scales, the Oswestry Disability Index, Multidimensional Pain Inventory, and the Beck Depression Inventory. It is anticipated that this study will provide novel information regarding the effects of chronic musculoskeletal pain, and treatment with opioids versus placebo, on selected neuroendocrine functions in men.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Primary Purpose: Treatment|
|Intervention ICMJE||Procedure: Blood Draw|
|Study Arms||Not Provided|
|Publications *||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.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Original Enrollment ICMJE||Same as current|
|Study Completion Date||October 18, 2007|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
EXCLUSION CRITERIA :
Usage of nonsteroidal anti-inflammatory drugs (NSAIDs) will be allowed at study entry and during the conduct of the study. Patients will be asked to refrain from using muscle relaxers, other opioids apart from the study drug (MS Contin), AED's (anti-epileptic drugs), TCAs (tricyclic antidepressants), SSRIs (selective serotonin reuptake inhibitors) and benzodiazepines for pain control during part II and III. Patients will also be asked to refrain from having local joint injections with steroids or other agents. Patients will be queried regarding their use of complementary and/or alternative medicine (CAM) treatments (e.g. acupuncture, chiropractic manipulations, herbs and botanicals, and mind-body interventions) at the start of the study and will be counseled against beginning CAM treatments during the study protocol. Starting any of these treatments during the study will be considered a study violation. The only exception will be for glucosamine and/or chondroitin.
|Ages||30 Years to 65 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00088296|
|Other Study ID Numbers ICMJE||040239
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Center for Complementary and Integrative Health (NCCIH)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||October 18, 2007|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP