Phase 1
N=105
CYP19A1 (Cytochrome P450 Family 19 Subfamily A Member 1) Gene and Pharmacogenetics of Response to Testosterone Therapy
Hypogonadism
Bottom Line
View on ClinicalTrials.gov: NCT01378299 ↗Enrolled (actual)
105
Serious AEs
17.1%
Results posted
Mar 2019
Primary outcome: Primary: Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene — 3.69; 4.13; 3.82; 0.38 percent change — p=<0.05
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Testosterone Cypionate (Drug)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- Male
- Sponsor
- VA Office of Research and Development
- Primary completion
- Nov 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene |
3.69; 4.13; 3.82; 0.38; 0.93; 0.08 | <0.05 sig |
| PRIMARY Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene |
4.72; 2.85; 3.74; -1.04; 0.64; 0.22 | <0.05 sig |
| SECONDARY Percent Change in Bone Mineral Density According to Body Mass Index (BMI) |
3.00; 4.90; 3.90; 0.14; 1.74; -0.27 | <0.05 sig |
| SECONDARY Percent Change in Prostate-specific Antigen (PSA) According to the rs700518 Polymorphism of the CYP19A1 Gene |
105.78; 58.52; 44.44 | <0.05 sig |
| SECONDARY Percent Change in Prostate-specific Antigen (PSA) According to the rs1062033 Polymorphism of the CYP19A1 Gene |
85.15; 62.86; 52.93 | <0.05 sig |
| SECONDARY Percent Change in Hematocrit According to the Genotype of the 700518 Polymorphism of the CYP19A1gene |
11.32; 9.71; 9.41 | <0.05 sig |
| SECONDARY Percent Change in Hematocrit According to re1062033 Polymorphism of the CYP19A1 Gene |
11.56; 9.67; 9.46 | <0.05 sig |
| SECONDARY Percent Change in Aromatase Gene Activity From the Buffy Coat According to the 700518 Polymorphism of the CYP19A1 Gene |
25.0; 65.25; 113.33 | — |
| SECONDARY Percent Change in Bone Turnover Markers According to the rs700518 Polymorphism of the CYP19A1 Gene |
41.47; 3.35; -9.75; 12.40; -31.22; -7.27 | <0.05 sig |
| SECONDARY Percent Change in Bone Turnover Markers According to the rs1062033 Polymorphism of the CYP19A1 Gene |
48.96; 5.89; -14.49; 33.59; -20.59; -26.96 | <0.05 sig |
| SECONDARY Percent Change in Bone Mineral Density According the Presence of Diabetes Mellitus |
4.05; 3.28; 1.81; 0.53; 1.63; -0.55 | <0.05 sig |
| SECONDARY Percent Change in Bone Turnover Markers According the Presence of Diabetes Mellitus |
73.55; 2.05; 20.54; -6.62 | <0.05 sig |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- Male Veterans with low total testosterone ( 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.
Data sourced from ClinicalTrials.gov (NCT01378299). 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.