Trial Outcomes & Findings for Testosterone Therapy and Bone Quality in Men With Diabetes and Hypogonadism (NCT NCT03887936)

Last Updated: 2025-12-23

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE4

Target enrollment

92 participants

Primary outcome timeframe

months 0, 6 and 12

Results posted on

2025-12-23

Participant Flow

Participants were recruited by flyers and letters from the Primary Care and Endocrine Clinics at the Michael E. DeBakey VA Medical Center. The study was open to enrollment on October 1, 2019 and closed on September 30, 2024.

There were 467 subjects who responded to our study advertisement. Three hundred ninety-five came for orientation, consent and screening, while 72 declined to come. Three hundred three were not enrolled; 271 failed our screening procedures from either laboratory tests or significant past medical history that constitutes an exclusion from the study, 21 did not finish the required screening tests and 11 decided not to proceed with the study.

Participant milestones

Participant milestones
Measure	Testosterone Arm Testosterone gel 1.62%: Testosterone gel 1.62%, apply 2 pumps to upper arm and shoulder.	Placebo Arm Matching placebo will be prepared by the Michael DeBakey VA Medical Center Pharmacy. Placebo: Matching placebo gel, apply 2 pumps to upper arm and shoulder
Overall Study STARTED	46	46
Overall Study Bone Quality Assessments	34	34
Overall Study COMPLETED	44	42
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Testosterone Arm Testosterone gel 1.62%: Testosterone gel 1.62%, apply 2 pumps to upper arm and shoulder.	Placebo Arm Matching placebo will be prepared by the Michael DeBakey VA Medical Center Pharmacy. Placebo: Matching placebo gel, apply 2 pumps to upper arm and shoulder
Overall Study Relocation	2	2
Overall Study Physician Decision	0	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Testosterone Therapy and Bone Quality in Men With Diabetes and Hypogonadism

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Testosterone Arm n=46 Participants Testosterone gel 1.62%: Testosterone gel 1.62%, apply 2 pumps to upper arm and shoulder.	Placebo Arm n=46 Participants Matching placebo will be prepared by the Michael DeBakey VA Medical Center Pharmacy. Placebo: Matching placebo gel, apply 2 pumps to upper arm and shoulder	Total n=92 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=68 Participants	0 Participants n=4 Participants	0 Participants n=219 Participants
Age, Categorical Between 18 and 65 years	46 Participants n=68 Participants	45 Participants n=4 Participants	91 Participants n=219 Participants
Age, Categorical >=65 years	0 Participants n=68 Participants	1 Participants n=4 Participants	1 Participants n=219 Participants
Age, Continuous	53.7 years STANDARD_DEVIATION 6.8 • n=68 Participants	55.5 years STANDARD_DEVIATION 6.6 • n=4 Participants	54.6 years STANDARD_DEVIATION 6.8 • n=219 Participants
Sex: Female, Male Female	0 Participants n=68 Participants	0 Participants n=4 Participants	0 Participants n=219 Participants
Sex: Female, Male Male	46 Participants n=68 Participants	46 Participants n=4 Participants	92 Participants n=219 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=68 Participants	9 Participants n=4 Participants	15 Participants n=219 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	40 Participants n=68 Participants	37 Participants n=4 Participants	77 Participants n=219 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=68 Participants	0 Participants n=4 Participants	0 Participants n=219 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=68 Participants	0 Participants n=4 Participants	0 Participants n=219 Participants
Race (NIH/OMB) Asian	4 Participants n=68 Participants	1 Participants n=4 Participants	5 Participants n=219 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=68 Participants	0 Participants n=4 Participants	0 Participants n=219 Participants
Race (NIH/OMB) Black or African American	18 Participants n=68 Participants	15 Participants n=4 Participants	33 Participants n=219 Participants
Race (NIH/OMB) White	24 Participants n=68 Participants	30 Participants n=4 Participants	54 Participants n=219 Participants
Race (NIH/OMB) More than one race	0 Participants n=68 Participants	0 Participants n=4 Participants	0 Participants n=219 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=68 Participants	0 Participants n=4 Participants	0 Participants n=219 Participants
Region of Enrollment United States	46 Participants n=68 Participants	46 Participants n=4 Participants	92 Participants n=219 Participants

PRIMARY outcome

Timeframe: months 0, 6 and 12

Population: There were 2 dropouts in the testosterone group thus, 44 participants finished the study. However, the imaging studies of one patient who finished the study is not optimum for FEA. There were 4 dropouts in the placebo thus, 42 participants finished the study. However, the investigators were unable to assess the finite element analysis in one patient as HRPQCT machine broke down when the participant came for final visit and refused to come again just for this assessment.

Outcome measures

Outcome measures
Measure	Testosterone Arm n=43 Participants Testosterone gel 1.62%: Testosterone gel 1.62%, apply 2 pumps to upper arm and shoulder.	Placebo Arm n=41 Participants Matching placebo will be prepared by the Michael DeBakey VA Medical Center Pharmacy. Placebo: Matching placebo gel, apply 2 pumps to upper arm and shoulder
Finite Element Analysis of Bone to Measure Bone Strength Change (%) from baseline in stiffness of radius at 6 months	1.2 % change Standard Deviation 8.7	1.6 % change Standard Deviation 11.6
Finite Element Analysis of Bone to Measure Bone Strength Change (%) from baseline in failure load of radius at 6 months	1.6 % change Standard Deviation 10.4	0.88 % change Standard Deviation 8.4
Finite Element Analysis of Bone to Measure Bone Strength Change (%) from baseline in stiffness of tibia at 6 months	-0.50 % change Standard Deviation 5.2	-0.45 % change Standard Deviation 6.8
Finite Element Analysis of Bone to Measure Bone Strength Change (%) from baseline in failure load of tibia at 6 months	-0.41 % change Standard Deviation 8.3	-0.36 % change Standard Deviation 5.8
Finite Element Analysis of Bone to Measure Bone Strength Change (%) from baseline in stiffness of the radius at 12 months	0.69 % change Standard Deviation 8.3	0.52 % change Standard Deviation 7.5
Finite Element Analysis of Bone to Measure Bone Strength Change (%) from baseline in failure load of radius at 12 months	0.74 % change Standard Deviation 8.3	0.09 % change Standard Deviation 8.5
Finite Element Analysis of Bone to Measure Bone Strength Change (%) from baseline in stiffness of tibia at 12 months	-0.01 % change Standard Deviation 5.3	0.44 % change Standard Deviation 5.0
Finite Element Analysis of Bone to Measure Bone Strength Change (%) from baseline in failure load of tibia in 12 months	0.08 % change Standard Deviation 4.4	0.37 % change Standard Deviation 4.4

SECONDARY outcome

Timeframe: months 0, 6 and 12

Two markers of bone resorption, serum C-telopeptide (CTX) and tartrate-resistant acid phosphatase 5b (TRAP5b) and 2 markers of bone formation osteocalcin (OCN) and N-terminal propeptide of type 1 collagen (P1NP) will be evaluated. These markers will be obtained at months 0, 6, and 12. Enzyme-linked immunosorbent assay will be used to measure serum CTX (serum crosslaps, Osteometer, Hawthorne, CA), tartrate-resistant acid phosphatase 5b (TRAP5b) (EIA) (Microvue Bonehealth, Quidel Corporation, Biosource); and serum osteocalcin (ALPCO, Salem, NH). Serum P1NP will be measured by competitive radioimmunoassay (UniqTM P1NP RIA, Immunodiagnostic Systems, Scottsdale, AZ). Coefficients of variations for these assays are \<10%.

Outcome measures

Outcome measures
Measure	Testosterone Arm n=32 Participants Testosterone gel 1.62%: Testosterone gel 1.62%, apply 2 pumps to upper arm and shoulder.	Placebo Arm n=31 Participants Matching placebo will be prepared by the Michael DeBakey VA Medical Center Pharmacy. Placebo: Matching placebo gel, apply 2 pumps to upper arm and shoulder
Markers of Bone Turnover to Measure Bone Metabolism Change (%) in osteocalcin at 12 months	7.8 % Change Standard Deviation 63	33.8 % Change Standard Deviation 87.5
Markers of Bone Turnover to Measure Bone Metabolism Change (%) in osteocalcin from baseline at 6 months	-9.7 % Change Standard Deviation 47.5	17.4 % Change Standard Deviation 88.8
Markers of Bone Turnover to Measure Bone Metabolism Change (%) in C-telopeptide (CTX) from baseline at 6 months	-81.6 % Change Standard Deviation 10.6	-80.4 % Change Standard Deviation 12.5
Markers of Bone Turnover to Measure Bone Metabolism Change (%) in CTX from baseline at 12 months	15.7 % Change Standard Deviation 64.2	-1.4 % Change Standard Deviation 51.7
Markers of Bone Turnover to Measure Bone Metabolism Change (%) in N-terminal peptide of type 1 collagen (P1NP) from baseline at 6 months	-8.6 % Change Standard Deviation 56.1	-31.1 % Change Standard Deviation 34.5
Markers of Bone Turnover to Measure Bone Metabolism Change (%) in P1NP from baseline at 12 months	2.31 % Change Standard Deviation 60.2	-23.1 % Change Standard Deviation 56.6

SECONDARY outcome

Timeframe: months 0, 6 and 12

Population: Out of the 44 participants who finished the study in testosterone arm, the cells did not stain in 3 patients. Out of the 42 participants who finished in the placebo, cells did not stain in one and the another was unable to provide enough blood sample for analysis at the end of the study

Osteoblast and osteoclast progenitor cells will be harvested from the serum at baseline, 6 and 12 months.

Outcome measures

Outcome measures
Measure	Testosterone Arm n=41 Participants Testosterone gel 1.62%: Testosterone gel 1.62%, apply 2 pumps to upper arm and shoulder.	Placebo Arm n=40 Participants Matching placebo will be prepared by the Michael DeBakey VA Medical Center Pharmacy. Placebo: Matching placebo gel, apply 2 pumps to upper arm and shoulder
Osteoblast and Osteoclast Progenitor Cells Which Are Cells Found in Bone Change (%) in osteoclast precursors from baseline at 6 months	68.4 % Change Standard Deviation 161.6	19.2 % Change Standard Deviation 104.4
Osteoblast and Osteoclast Progenitor Cells Which Are Cells Found in Bone Change (%) in osteoclast precursors from baseline at 12 months	59.1 % Change Standard Deviation 161.0	56.0 % Change Standard Deviation 130.1
Osteoblast and Osteoclast Progenitor Cells Which Are Cells Found in Bone Change (%) in osteoblast progenitor cells from baseline at 12 months	10.8 % Change Standard Deviation 55.2	-10.4 % Change Standard Deviation 29.5
Osteoblast and Osteoclast Progenitor Cells Which Are Cells Found in Bone Change (%) in osteoblast progenitor cells from baseline at 6 months	5.1 % Change Standard Deviation 40.5	-4.4 % Change Standard Deviation 36.9

Adverse Events

Testosterone Arm

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo Arm

Serious events: 4 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Testosterone Arm n=46 participants at risk Testosterone gel 1.62%: Testosterone gel 1.62%, apply 2 pumps to upper arm and shoulder.	Placebo Arm n=46 participants at risk Matching placebo will be prepared by the Michael DeBakey VA Medical Center Pharmacy. Placebo: Matching placebo gel, apply 2 pumps to upper arm and shoulder
Blood and lymphatic system disorders Lymphocytic leukemia	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.
Infections and infestations Sepsis	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.
Gastrointestinal disorders Vomiting and constipation secondary to gastroparesis	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.
Endocrine disorders Neuroendocrine tumor	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.
Gastrointestinal disorders Vomiting and bloody stools	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.
Vascular disorders Hypotension	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.

Other adverse events

Additional Information

Dr, Reina Villareal

Michael E. DeBakey VA Medical Center

Phone: 314-313-4550

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Testosterone Arm n=46 participants at risk Testosterone gel 1.62%: Testosterone gel 1.62%, apply 2 pumps to upper arm and shoulder.	Placebo Arm n=46 participants at risk Matching placebo will be prepared by the Michael DeBakey VA Medical Center Pharmacy. Placebo: Matching placebo gel, apply 2 pumps to upper arm and shoulder
Musculoskeletal and connective tissue disorders Fracture of greater trochanter after a fall	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.
Musculoskeletal and connective tissue disorders head trauma, rib pain and laceration of forehead after assault by the neighbor	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.
Musculoskeletal and connective tissue disorders C6-7 and rotator cuff surgeries from an injury sustained before he was enrolled in the study	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.
Musculoskeletal and connective tissue disorders C7-T1 disc injury from MVA	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.
Musculoskeletal and connective tissue disorders Pain in the groin area after a car accident	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.
Musculoskeletal and connective tissue disorders Outpatient knee surgery for meniscal tear.	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.
Musculoskeletal and connective tissue disorders Lumbar 4 vertebral fracture after picking-up a 375 lb. patients during an emergency	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.
Musculoskeletal and connective tissue disorders Left biceps tendon tear	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.
Musculoskeletal and connective tissue disorders Achilles tendon rupture	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.
Skin and subcutaneous tissue disorders Pain and rashes at the site of drug application	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.	4.3% 2/46 • Number of events 2 • Through study completion, i.e. approximately, 1 year.
Psychiatric disorders Anxious and having anger issues	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.
Psychiatric disorders Trouble sleeping and mood swings	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.
Infections and infestations Abscess on he right breast	2.2% 1/46 • Number of events 1 • Through study completion, i.e. approximately, 1 year.	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.
Renal and urinary disorders High prostate-specific antigen	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.	4.3% 2/46 • Number of events 2 • Through study completion, i.e. approximately, 1 year.
Blood and lymphatic system disorders High hematocrit	4.3% 2/46 • Number of events 2 • Through study completion, i.e. approximately, 1 year.	0.00% 0/46 • Through study completion, i.e. approximately, 1 year.