Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
The purpose of this randomized controlled clinical trial is to evaluate the effects of clomiphene citrate compared to placebo (substance without active medication) in men who are taking pain medication (opioids) for chronic pain conditions and who have low blood testosterone levels.
The condition of men having low testosterone with long-term pain medication (opioid) usage is called opioid-induced androgen deficiency (OPIAD). Low testosterone can be caused by pain medication effects on part of the brain (hypothalamic-pituitary axis) which ultimately result in decreased testosterone production by the testes. Typical symptoms of low testosterone (hypogonadism) may include decreased muscle mass, increased fat, osteoporosis, anemia, erectile dysfunction, delayed ejaculation. In addition, men with low testosterone may experience decreased attention, and decreased libido, fatigue, and depressed mood. Few studies have looked at hormonal changes caused by long-term opioid usage in men.
Clomiphene citrate, a selective estrogen receptor modulator (SERM) oral medication which inhibits estrogen effects (feedback) on the brain, has been identified by prior studies to raise testosterone in men with low testosterone (due to reasons other than chronic pain medication). Clomiphene citrate is also known to lead to increased sperm production in men with low testosterone unlike testosterone topical or injection medications. Although clomiphene citrate has been studied in hypogonadal men with beneficial outcomes and minimal side effects, no group has previously studied clomiphene citrate as treatment in patients with OPIAD.
Drug: Clomiphene citrate
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Clomiphene Citrate for the Treatment of Opioid-Induced Androgen Deficiency: Randomized Controlled Clinical Trial|
- Serum total testosterone (change from baseline) [ Time Frame: Baseline, 2 weeks, 1 month, 3 months ] [ Designated as safety issue: No ]Morning venipuncture of serum total testosterone to assess change over time.
- Other hormonal profile (change from baseline) [ Time Frame: Baseline, 2 weeks, 1 month, 3 months ] [ Designated as safety issue: No ]Serum free testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle stimulating hormone (FSH), dihydrotestosterone (DHT), estradiol, prolactin, adrenocorticotropic hormone (ACTH), cortisol, insulin like growth factor 1 (IGF-1), complete blood count (CBC), cholesterol, B-endorphin, met-enkephalin. Each lab test is intended to assess change over time.
- Urine studies (change from baseline) [ Time Frame: Baseline, 2 weeks, 1 month, 3 months ] [ Designated as safety issue: No ]24 hour urine aldosterone/cortisol to assess change over time.
- Semen analysis (sperm count, concentration, motility, morphology: change from baseline) [ Time Frame: Baseline, 2 weeks, 1 month, 3 months ] [ Designated as safety issue: No ]This portion of the study will be completed with patient consent and may be omitted if desired by the patient.
- Questionnaires- self-administered [ Time Frame: Baseline, 2 weeks, 1 month, 3 months ] [ Designated as safety issue: No ]The following validated questionnaires will be used: Androgen Deficiency in the Aging Male (ADAM) questionnaire (with 10 yes/no questions assessing low testosterone symptoms), IIEF-5 (International Index of Erectile Function 5 question survey each with 1 to 5 answers, summed: score of 22-25 demonstrates no erectile dysfunction, score of 5-7 demonstrates severe erectile dysfunction), and Visual Analog Scale (VAS, scored 0=no pain to 10=worst possible pain). Overall, study subjects will be assessed for possible change in hypogonadal, sexual function, and pain symptoms.
|Study Start Date:||August 2013|
|Estimated Study Completion Date:||June 2014|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
Experimental: Clomiphene citrate
The initial dose of clomiphene citrate will be 25 mg (po, pill by mouth) every other day. This will be started at visit 2, week 0 of the study following diagnosis of low baseline testosterone (serum total testosterone <350 ng/dl in men <55 years, <300 ng/dl in men 55-65 years). Clomiphene citrate dose will be titrated up to a maximum of 50 mg daily according to serum total testosterone levels measured at follow-up visits during the 3 month duration of the study.
Drug: Clomiphene citrate
Placebo Comparator: Placebo
Placebo pill will be administered (po, pill by mouth) every other day starting at week 0 of the study in men diagnosed with low testosterone. Treatment will be delayed in these men until the 3 month completion of the study, at which time this group may also receive testosterone replacement therapy.
Placebo pill that will have appearance identical to the treatment pill but will not contain active medication.
Other Name: Sugar pill
Chronic nonmalignant pain is a widespread issue affecting 15-30% of the population. Many patients with chronic pain are responsive to first-line combination of physical modalities and non-opioid analgesics. Up to 20% of these patients, however, require opioid therapy for adequate pain relief. The use of long-acting opioids, including morphine sulfate, oxycodone, fentanyl, and methadone, although effective for pain control, carries risks of addiction, tolerance, and systemic side effects including nausea, itching, constipation, and hypogonadotropic hypogonadism with consequent testosterone depletion (in up to 86% of patients taking chronic pain medication) leading to the multiple adverse effects. Opioid-induced androgen deficiency (OPIAD), occurs with high frequency and persistence, and commonly remains undiagnosed in the pain clinic. Low testosterone may be treated using exogenous testosterone (topical or gel) or other medications such as selective estrogen receptor modulators (i.e. clomiphene citrate). While both medication types increase serum testosterone levels, clomiphene citrate is known to benefit sperm parameters in hypogonadal men while exogenous testosterone is known to inhibit sperm production. Few studies have examined the hormonal changes caused by long-term opioid usage in men, and no studies have formally studied clomiphene citrate for this patient population.
|Contact: Matthew Wosnitzer, MDfirstname.lastname@example.org|
|United States, New York|
|Weill Cornell Medical College, Department of Urology||Recruiting|
|New York, New York, United States, 10065|
|Contact: Matthew Wosnitzer, MD 212-746-5470|
|Principal Investigator: Peter N Schlegel, MD|
|Principal Investigator:||Peter N Schlegel, MD||Weill Medical College of Cornell University|