Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
Condition: Hypogonadism; Opioid-Related Disorders; Male Infertility
MeSH terms: Infertility; Infertility, Male; Hypogonadism; Opioid-Related Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Clomiphene citrate; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Placebo pill that will have appearance identical to the treatment pill but will not contain active medication.
Other intervention name(s): Clomid; Milophene; Serophene; Sugar pill
Intervention MeSH terms: Clomiphene; Enclomiphene; Zuclomiphene
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Chronic pain; Low testosterone; Hypogonadism; Opioid analgesics; Narcotics; Opioid-induced androgen deficiency; OPIAD; Male infertility; Clomiphene citrate; Selective Estrogen Receptor Modulators; Testosterone replacement therapy