Testosterone Therapy and Bone Quality in Men With Diabetes and Hypogonadism

NCT03887936 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: ENDB-009-18F1I01CX001665-01A2
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

Low testosterone and diabetes mellitus are each associated with increased risk for fractures. Men with diabetes mellitus are commonly found to have low testosterone as well. Testosterone has been shown to improve the bone health of patients with low testosterone but has not been tested in patients who also have diabetes mellitus in addition to low testosterone. To date, there is no treatment that is specifically recommended for bone disease among patients with diabetes. This study will evaluate the effect of testosterone on the bone health of male Veterans who have both diabetes and low testosterone, both of which are highly prevalent in this subset of the population.

Conditions

Type 2 Diabetes Mellitus; Hypogonadism

Keywords

diabetes mellitus; hypogonadism; testosterone; bone quality

Outcome Measures

Primary Outcomes (1)

• Finite Element Analysis of Bone to Measure Bone Strength

  The FEA (or FEA) is a surrogate measure of strength using computational biomechanical principles and integrate bone morphology and bone mass to calculate bone strength under various loading conditions normally seen in daily living activities. In addition, the ratio of load to strength can be calculated by using patient information (i.e. weight and height) and FEA derived bone strength to mechanistically simulate bone failure and thus, whether fracture is likely during a given activity. Using high-resolution peripheral quantitative computer tomography (HRPQCT) we will compute for FEA, using FEA software with images generated using Image Processing Language to estimate the biomechanical properties of the bone. Each bone voxel will be converted to hexahedral finite elements with linear-elastic and isotropic material behavior. The FEA model will be subject to uniaxial compression and stiffness and failure load will be estimated. FEA will be assessed at months 0, 6 and 12.

  months 0, 6 and 12

Secondary Outcomes (2)

• Markers of Bone Turnover to Measure Bone Metabolism

  months 0, 6 and 12

• Osteoblast and Osteoclast Progenitor Cells Which Are Cells Found in Bone

  months 0, 6 and 12

Study Arms (2)

Testosterone arm

EXPERIMENTAL

Testosterone gel 1.62%

Drug: Testosterone gel 1.62%

Placebo arm

PLACEBO COMPARATOR

Matching placebo will be prepared by the Michael DeBakey VA Medical Center Pharmacy.

Drug: Placebo

Interventions

Placebo DRUG

Matching placebo gel, apply 2 pumps to upper arm and shoulder

Placebo arm

Testosterone gel 1.62% DRUG

Testosterone gel 1.62%, apply 2 pumps to upper arm and shoulder.

Also known as: Androgel

Testosterone arm

Eligibility Criteria

• Age: 35 Years - 70 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male veterans only
• to 70 years old
• With an average fasting morning T level from 2 measurements of \<300 ng/dl taken at least a day apart
• symptoms of hypogonadism as assessed using the androgen deficiency in aging male (ADAM) questionnaire
• Participants should have
• T2D
• an A1C of \<11.5 %
• a fasting blood sugar of 180 mg/dl
• body mass index (BMI) \<40 kg/m2
• with DM of 15 years duration or less to target men who have relatively less complications from long-term DM

You may not qualify if:

• history of prostate or breast cancer
• history of testicular disease
• untreated severe sleep apnea
• ongoing illness that could prevent the subject from completing the study
• a hematocrit of \>50%
• prostate-related findings as:
• a palpable prostate nodule on digital rectal exam (DRE)
• serum PSA of 4.0 ng/ml
• International Prostate Symptom Score (IPSS) \>19 (severe)
• on androgen therapy or selective androgen receptor modulators
• on medications that affect bone metabolism such as:
• estrogen
• selective estrogen receptor modulator as:
• raloxifene
• aromatase inhibitors

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030-4211, United States

Location

Related Publications (10)

• Russo V, Chen R, Armamento-Villareal R. Hypogonadism, Type-2 Diabetes Mellitus, and Bone Health: A Narrative Review. Front Endocrinol (Lausanne). 2021 Jan 18;11:607240. doi: 10.3389/fendo.2020.607240. eCollection 2020.

  PMID: 33537005 BACKGROUND

• Deepika F, Ballato E, Colleluori G, Aguirre L, Chen R, Qualls C, Villareal DT, Armamento-Villareal R. Baseline Testosterone Predicts Body Composition and Metabolic Response to Testosterone Therapy. Front Endocrinol (Lausanne). 2022 Jul 11;13:915309. doi: 10.3389/fendo.2022.915309. eCollection 2022.

  PMID: 35898448 BACKGROUND

• Bathina S, Armamento-Villareal R. The complex pathophysiology of bone fragility in obesity and type 2 diabetes mellitus: therapeutic targets to promote osteogenesis. Front Endocrinol (Lausanne). 2023 Jul 20;14:1168687. doi: 10.3389/fendo.2023.1168687. eCollection 2023.

  PMID: 37576965 BACKGROUND

• Deepika F, Bathina S, Armamento-Villareal R. Novel Adipokines and Their Role in Bone Metabolism: A Narrative Review. Biomedicines. 2023 Feb 20;11(2):644. doi: 10.3390/biomedicines11020644.

  PMID: 36831180 BACKGROUND

• Bathina S, Prado M, Fuenmayor Lopez V, Colleluori G, Aguirre L, Chen R, Villareal DT, Armamento-Villareal R. PRDM16 Enhances Osteoblastogenic RUNX2 via Canonical WNT10b/beta-CATENIN Pathway in Testosterone-Treated Hypogonadal Men. Biomolecules. 2025 Jan 8;15(1):79. doi: 10.3390/biom15010079.

  PMID: 39858473 BACKGROUND

• Chen R, Armamento-Villareal R. Obesity and Skeletal Fragility. J Clin Endocrinol Metab. 2024 Jan 18;109(2):e466-e477. doi: 10.1210/clinem/dgad415.

  PMID: 37440585 BACKGROUND

• Russo V, Colleluori G, Chen R, Mediwala S, Qualls C, Liebschner M, Villareal DT, Armamento-Villareal R. Testosterone therapy and bone quality in men with diabetes and hypogonadism: Study design and protocol. Contemp Clin Trials Commun. 2021 Jan 20;21:100723. doi: 10.1016/j.conctc.2021.100723. eCollection 2021 Mar.

  PMID: 33718653 RESULT

• Ballato E, Deepika FNU, Russo V, Fleires-Gutierrez A, Colleluori G, Fuenmayor V, Chen R, Villareal DT, Qualls C, Armamento-Villareal R. One-Year Mean A1c of > 7% is Associated with Poor Bone Microarchitecture and Strength in Men with Type 2 Diabetes Mellitus. Calcif Tissue Int. 2022 Sep;111(3):267-278. doi: 10.1007/s00223-022-00993-x. Epub 2022 Jun 4.

  PMID: 35665818 RESULT

• Bathina S, Lopez VF, Prado M, Ballato E, Colleluori G, Tetlay M, Villareal DT, Mediwala S, Chen R, Qualls C, Armamento-Villareal R. Health implications of racial differences in serum growth differentiation factor levels among men with obesity. Physiol Rep. 2024 Dec;12(23):e70124. doi: 10.14814/phy2.70124.

  PMID: 39668628 RESULT

• Ballato E, Deepika F, Prado M, Russo V, Fuenmayor V, Bathina S, Villareal DT, Qualls C, Armamento-Villareal R. Circulating osteogenic progenitors and osteoclast precursors are associated with long-term glycemic control, sex steroids, and visceral adipose tissue in men with type 2 diabetes mellitus. Front Endocrinol (Lausanne). 2022 Sep 12;13:936159. doi: 10.3389/fendo.2022.936159. eCollection 2022.

  PMID: 36171900 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypogonadism; Diabetes Mellitus

Interventions

Testosterone

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

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

reina.villareal@bcm.edu

314-313-4550

Study Officials

• Reina C. Villareal, MD

  Michael E. DeBakey VA Medical Center, Houston, TX

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: No other parties will be masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Double-blind randomized placebo-controlled study comparing the effect of testosterone therapy in men with both type 2 diabetes mellitus and hypogonadism on bone quality, bone turnover markers and circulating osteoblast and osteoclast progenitors.

Study Record Dates

• First Submitted: March 21, 2019
• First Posted: March 25, 2019
• Study Start: October 1, 2019
• Primary Completion: October 8, 2025
• Study Completion: October 8, 2025
• Last Updated: April 29, 2026
• Results First Posted: December 23, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)