CYP19A1 (Cytochrome P450 Family 19 Subfamily A Member 1) Gene and Pharmacogenetics of Response to Testosterone Therapy

Completed · Phase 1

Conditions studied: Hypogonadism

In brief

Testosterone (T) replacement prevents bone loss and relieves symptoms associated with androgen deficiency in male patients with hypogonadism, but at the expense of an increase in prostate-related adverse events and in the hematocrit values above the normal which may lead to bad circulatory outcomes. Most of the effects of T on the male skeleton are mediated by its conversion to estradiol (E2) by the enzyme aromatase. Genetic variations in the aromatase (CYP19A1) gene result in enzymes with variable activity and variable levels of E2 and T. This project is designed to determine if genetic variations in the CYP19A1 gene will result in differences in the skeletal response and incidence of side effects from T treatment in patients with low T. A large number of male Veterans are on T. Results from this project will help identify patients who would benefit from the therapy from those at risk for side effects, and would definitely have an impact in the future care of these patients and male patients in general once genetic profiling becomes part of the standard of care.

Key facts

Study ID

NCT01378299

Run by

VA Office of Research and Development

People needed

105

Starts

2011-10-01

Expected to finish

2017-11-07

Last updated by the study team

2019-03-05

Who can join

Age: 40 and older, up to 75. Sex: male. Healthy volunteers: accepted.

You may qualify if…

• Male Veterans with low total testosterone (<300 ng/dl) as defined by the Endocrine Society, who are between 40-75 years of age.
• These patients must be ambulatory; and be willing and able to provide written informed consent.

You may not qualify if…

• history of prostate cancer, breast cancer
• history of testicular disease
• untreated sleep apnea
• any ongoing illness that, in the opinion of the investigator, could prevent the subject from completing the study
• patients with a hematocrit of more than 50% (2010 Endocrine Society Guidelines)
• prostate-related findings of a palpable prostate nodule on exam, a serum PSA of 4.0 ng/ml or more, International Prostate Symptom Score >8(9), urinary postvoid residual by ultrasound of >149 ml, or an abnormal transrectal ultrasound
• patients who are on androgen replacement therapy, selective androgen receptor modulator, or finasteride
• patients currently on medications that affects bone metabolism such as:
• estrogen
• the selective estrogen receptor modulator (SERM) as raloxifene
• use of bisphosphonates (i.e. risedronate, alendronate, zoledronic acid and pamidronate)
• within two years of study entry
• aromatase inhibitors
• GnRH analogs
• glucocorticoids of at least 5 mg daily for one month or more
• anabolic steroids
• dilantin
• warfarin
• patients with diseases known to interfere with bone metabolism as hyperparathyroidism, untreated hyperthyroidism, osteomalacia, chronic liver disease, renal failure, hypercortisolism, malabsorption and immobilization
• those with current alcohol use of more than 3 drinks per day (62).
• history of documented coronary artery disease at high risk for recurrence
• Subjects with osteoporosis or a BMD T-score of -2.5 in the lumbar spine, total femur or femoral neck as well as those patients with a history of osteoporosis-related fractures (spine, hip or wrist) or vertebral deformities on lateral spine radiographs deemed as fragility fractures by the team principal investigator.
• history of documented coronary artery disease at high risk for recurrence, history of deep vein thrombosis and cerebrovascular event.

Where it is running

• New Mexico VA Health Care System, Albuquerque, NM — Albuquerque, New Mexico, United States
• Michael E. DeBakey VA Medical Center, Houston, TX — Houston, Texas, United States

Full record on ClinicalTrials.gov

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