Phase 2
N=13
Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
Hypogonadism · Opioid-Related Disorders · Male Infertility
Bottom Line
View on ClinicalTrials.gov: NCT01880086 ↗Enrolled (actual)
13
Serious AEs
0.0%
Results posted
Jun 2017
Primary outcome: Primary: Serum Total Testosterone (Change From Baseline) — 322.5; 179.8 ng/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Clomiphene citrate (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Male
- Sponsor
- Weill Medical College of Cornell University
- Primary completion
- Mar 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Serum Total Testosterone (Change From Baseline) |
322.5; 179.8 | — |
| SECONDARY Other Hormonal Profile (Change From Baseline) |
3.3; 2.2 | — |
| SECONDARY Androgen Deficiency in the Aging Male (ADAM) Questionnaire |
8.0; 8.0 | — |
| SECONDARY Hematocrit (%) |
35.2; 42.3 | — |
| SECONDARY Estradiol |
23; 25.2 | — |
| SECONDARY Sexual Health Inventory for Men (SHIM) Questionnaire |
12.2; 18.5 | — |
| SECONDARY Men's Sexual Health Questionnaire (MSHQ) Questionnaire |
7.0; 8.8 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Male
- 18 years to 65 years
- Low testosterone as defined by criteria (serum total testosterone =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 = 55 and =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).
Data sourced from ClinicalTrials.gov (NCT01880086). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.