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

NCT01378299 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: SPLC-001-10S
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Hypogonadism

Keywords

testosterone

Outcome Measures

Primary Outcomes (2)

• Percent Change in Bone Mineral Density (BMD) According to rs700518 Polymorphism in the CYP19A1 Gene

  Percent change in bone mineral density from baseline to 18 months

  form baseline to 18 months

• Percent Change in Bone Mineral Density (BMD) According to the rs1062033 Polymorphism in the CYP19A1 Gene

  Percent change in bone mineral density from baseline to 18 months.

  baseline to 18 months

Secondary Outcomes (10)

• Percent Change in Bone Mineral Density According to Body Mass Index (BMI)

  baseline to 18 months

• Percent Change in Prostate-specific Antigen (PSA) According to the rs700518 Polymorphism of the CYP19A1 Gene

  From baseline to 18 months

• Percent Change in Prostate-specific Antigen (PSA) According to the rs1062033 Polymorphism of the CYP19A1 Gene

  from baseline to 18 months

• Percent Change in Hematocrit According to the Genotype of the 700518 Polymorphism of the CYP19A1gene

  baseline to 18 months

• Percent Change in Hematocrit According to re1062033 Polymorphism of the CYP19A1 Gene

  Baseline to 18 months

Study Arms (1)

Arm 1: Testosterone Cypionate

EXPERIMENTAL

All patients who qualify for the study will receive testosterone cypionate

Drug: Testosterone Cypionate

Interventions

Testosterone Cypionate DRUG

Testosterone cypionate was administered at 200 mg by intramuscular injection every 2 weeks. DEPo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)-cyclopentylpropionate ester of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils. The chemical name for testosterone cypionate is androst-4-en-3-one,17-(3-cyclopentyl-1oxopropoxy)-, (178)-. Its molecular formula is CvH400a, and the molecular weight of 412.61.

Also known as: depo testosterone

Arm 1: Testosterone Cypionate

Eligibility Criteria

• Age: 40 Years - 75 Years
• Gender Eligibility Details: Male Veterans with low total testosterone (\<300 ng/dl) as defined by the Endocrine Society, who are between 40-75 years of age.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

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

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Baylor College of Medicine: collaborator

Study Sites (2)

New Mexico VA Health Care System, Albuquerque, NM

Albuquerque, New Mexico, 87108-5153, United States

Location

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Joad S, Ballato E, Deepika F, Gregori G, Fleires-Gutierrez AL, Colleluori G, Aguirre L, Chen R, Russo V, Fuenmayor Lopez VC, Qualls C, Villareal DT, Armamento-Villareal R. Hemoglobin A1c Threshold for Reduction in Bone Turnover in Men With Type 2 Diabetes Mellitus. Front Endocrinol (Lausanne). 2021 Dec 28;12:788107. doi: 10.3389/fendo.2021.788107. eCollection 2021.

  PMID: 35027909 DERIVED

• Colleluori G, Aguirre L, Napoli N, Qualls C, Villareal DT, Armamento-Villareal R. Testosterone Therapy Effects on Bone Mass and Turnover in Hypogonadal Men with Type 2 Diabetes. J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3058-e3068. doi: 10.1210/clinem/dgab181.

  PMID: 33735389 DERIVED

MeSH Terms

Conditions

Hypogonadism

Interventions

testosterone 17 beta-cypionate; Testosterone Propionate

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Testosterone; Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Reina Villareal, MD
• Organization: Michael E. DeBakey VA Medical Center

reina.villareal@va.gov

713-794-7534

Study Officials

• Reina C Villareal, MD

  New Mexico VA Health Care System, Albuquerque, NM

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2011
• First Posted: June 22, 2011
• Study Start: October 1, 2011
• Primary Completion: November 7, 2016
• Study Completion: November 7, 2017
• Last Updated: March 5, 2019
• Results First Posted: March 5, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will share

Locations

US (2)