Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration

This is an interventional treatment trial for Hypogonadism focused on measuring Chronic pain, Low testosterone, Hypogonadism, Opioid analgesics, Narcotics, Opioid-induced androgen deficiency, OPIAD, Male infertility, Clomiphene citrate, Selective Estrogen Receptor Modulators, Testosterone replacement therapy Read More

Inclusion Criteria:

• Male
• 18 years to 65 years
• Low testosterone as defined by criteria (serum total testosterone <350 ng/dl in men <55 years, <300 ng/dl in men 55-65 years)
• EITHER taking opioid pain medication (see A below) OR planning to start new pain medication regimen (see B below)
• A) EITHER continuous opioid treatment for chronic nonmalignant pain for >=6 months receiving one of several specified opioid regimens for the past 1 month (including >=20 mg/day of oral methadone, >=30 mg/day of oral sustained release oxycodone, >=30 mg/day of oral morphine sulfate, >=6 mg/day of oral dilaudid or >= 8 mg/day of dilaudid ER, or >=25 mcg/hr of transdermal fentanyl or buprenorphine, or intrathecal morphine pump)
• B) OR the pain management physician is planning to start pain medication (opioid or non-opioid pain therapy) but you have not received it yet. If this is the case, your testosterone will be checked before starting and during 1 month of pain therapy to determine if you have low testosterone to qualify to begin medication (clomiphene or placebo) treatment in this study.
• BMI (20-35 kg/m2)
• Presence of clear secondary hypogonadism with hypogonadal symptoms and low total testosterone level (confirmed with morning testosterone level <= 350 ng/dL for men age >= 55 and <= 300ng/dl for men age 55-65) or total testosterone <=200 ng/dl (regardless of symptoms). Additionally luteinizing hormone (LH) should be <15 mIU (milli-International unit )/mL (at baseline only). Symptoms of hypogonadism include fatigue, decreased energy level/endurance, depressed mood, decreased libido, erectile dysfunction.
• Chronic nonmalignant pain etiology includes rheumatoid arthritis, osteoarthritis, spinal stenosis, polymyalgia, complex region pain syndrome I and II, neurinoma, phantom limb pain, neuropathic pain of other origin, scoliosis, neck pain, failed back surgery, or chronic pancreatitis.
• All patients must have ability to complete the study in compliance with the protocol, and the ability to understand and provide written informed consent.

Exclusion Criteria:

• Chronic pain of malignant etiology (cancer-related)
• Preexisting testosterone deficiency
• Concomitant use of medication that could interfere with testosterone levels including antidepressant medication, spironolactone, cimetidine, clomiphene (use in the past 1 year), human chorionic gonadotropin (hCG), androgen, estrogen, anabolic steroid, 5-alpha-reductase inhibitors such as finasteride, dehydroepiandrosterone (DHEA), testosterone therapy (topical testosterone within 7 days of study, injectable testosterone within 6 months of study),
• Uncontrolled hypertension
• Clinically significant abnormal findings on screening examination based on the Investigator's assessment
• Known hypersensitivity to clomiphene
• Symptomatic cataracts
• Presence or history of known hyperprolactinemia with or without a tumor
• End-stage renal disease
• Any contraindication to testosterone supplementation therapy
• Absolute contraindications to hormone supplementation therapy which include active prostate cancer (or suspicion of prostate disease unless ruled out by biopsy), prostatic specific antigen (PSA)>=3.6, breast cancer, hematocrit>=51% (hemoglobin>=17 g/dL), uncontrolled congestive heart failure (CHF), myocardial infarction, acute coronary event, unstable angina, coronary revascularization procedure in the preceding 6 months, untreated obstructive sleep apnea, high risk of prostate cancer (ethnicity or family history), or severe lower urinary tract symptoms (AUA symptom score>19).