Testosterone Plus Finasteride Treatment After Spinal Cord Injury

Higher-Than-Replacement Testosterone Plus Finasteride Treatment After SCI

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02248701

Enrollment

Registered

2014-09-25

Start date

2017-04-27

Completion date

2021-08-13

Last updated

2023-09-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Central Nervous System Diseases, Endocrine System Diseases, Genital Diseases, Male, Gonadal Disorders, Hypogonadism, Nervous System Diseases, Spinal Cord Diseases, Spinal Cord Injuries, Spinal Cord Injury, Trauma, Nervous System, Wounds and Injuries

Keywords

Testosterone, Testosterone enanthate, Testosterone undecanoate, Testosterone 17 beta-cypionate, Methyltestosterone, Androgens, Hormones, Hormone Substitutes, and Hormone Antagonists, Physiologic Effects of Drugs, Pharmacologic Actions, Antineoplastic Agents, Hormonal, Antineoplastic Agents, Therapeutic Uses, Anabolic Agents, Testosterone Replacement Therapy, Dual Energy X ray Absorptiometry, Lean Tissue Mass, Body Composition, Lipid and Glucose profile, Muscle Strength, 5-alpha Reductase, Muscle Mass, Bone Mineral Density, Adipose Tissue, Body Fat, Density, Bone, Bone Formation, Bone Resorption, Bone Density Conservation Agents, Magnetic Resonance Imaging, Muscle, Skeletal, Bone and Bones, Gait, Walking, Locomotion, Motor Activity

Brief summary

The purpose of this study is to determine whether testosterone plus finasteride treatment will improve musculoskeletal health, neuromuscular function, body composition, and metabolic health in hypogonadal men who have experienced ambulatory dysfunction subsequent to incomplete spinal cord injury. The investigators hypothesize that this treatment will improve bone mineral density, enhance muscle size and muscle function, and improve body composition, without causing prostate enlargement.

Detailed description

Men with spinal cord injury (SCI) experience a high prevalence of hypogonadism which influences the neural, muscular, skeletal, and body composition deficits that occur after injury. It remains unknown whether testosterone administration improves bone mineral density, muscle mass and muscle function, and body composition / metabolic health in hypogonadal men who have experienced ambulatory dysfunction subsequent to incomplete spinal cord injury. In addition, it is unknown whether testosterone or the 5-alpha reduced metabolite dihydrotestosterone (an endogenous metabolite of testosterone) mediate effects in these and other tissues. For this study hypogonadal men with motor incomplete spinal cord injury who present with ambulatory dysfunction will be randomized to receive testosterone plus the 5-alpha reductase inhibitor finasteride or a placebo treatment for 12 months. Testosterone or placebo injection will be administered weekly; finasteride or placebo will be administered daily. Participants will be assessed at study entry and at 1-6 month intervals thereafter. Assessments will include measurements such as a dual energy x-ray absorptiometry (DEXA) scan, MRI scan, and muscle performance tests. Participants will also have several safety tests, including electrocardiogram (EKG) for cardiac electrophysiology, prostate digital rectal exam and prostate ultrasound sizing for prostate health, and blood tests to assess hematocrit, liver enzymes (AST and ALT), prostate specific antigen (PSA), cholesterol, and other health markers.

Interventions

DRUGPlacebo injection

Subjects receive placebo (weekly) by intramuscular injection

DRUGPlacebo pill

Subjects receive placebo pill (daily) orally

DRUGTestosterone Enanthate

Subjects receive testosterone (125 mg/week) by intramuscular injection

DRUGFinasteride

Subjects receive finasteride (5 mg/day) orally

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

MALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Male \> 18 years of age * Traumatic, vascular, or orthopedic spinal cord injury between C2-L3 \>12 months prior to enrollment * Motor incomplete spinal cord (AIS C/D) * Ambulatory dysfunction * Medically stable condition that is asymptomatic for bladder infection, decubiti, cardiopulmonary disease, or other significant medical conditions * Serum total testosterone (\<325 ng/dL) or bioavailable testosterone (\<70 ng/dL)

Exclusion criteria

* Currently participating in another research protocol that may influence study outcomes * Life expectancy \<1 year * History of or current congenital spinal cord injury or other degenerative spinal disorder * Diagnosis of multiple sclerosis, amyotrophic lateral sclerosis, or other neurologic impairment/injury * History of venous thromboembolism within the last 6 months, specifically deep venous thromboembolism and pulmonary embolism, history of recurrent venous thromboembolism or know hereditary thrombophilia * Poorly compensated or uncontrolled cardiovascular disease * Any major cardiovascular event within the last 12 months (defined as a history of acute myocardial infarction, any cardiac revascularization procedure including angioplasty, stenting, or coronary artery bypass grafting, hospitalization due to unstable angina, transient ischemic attack, or stroke) * Any angina that is not controlled on a current medical regimen (Canadian class II, III, or IV) * New York Heart Association (NYHA) class III or IV congestive heart failure * Systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mm Hg * Poorly controlled arrhythmia * Severe valvular disease * LDL cholesterol \>160 mg/dl with known history of any major cardiovascular event, as defined above, within the last 12 months * Baseline EKG findings (e.g. left bundle branch block) or marked EKG abnormalities that would preclude serial screening for occult ischemic events * Current prostate, breast, or other organ cancer * History of prostate, breast, or other organ cancer, with the exceptions of completely resolved basal or squamous cell carcinoma for a duration of \>24 months or completely resolved melanoma for a duration of \>24 months * Serum prostate-specific antigen (PSA) \>3.0 ng/ml * History of benign prostate enlargement (BPE) \>40cc, evaluated via TRUS * Hematocrit \>47% * Liver enzymes (AST / ALT) above normal upper limit * Creatinine \>1.4 mg/dL * Serum calcium \>10.5 mg/dL * Gynecomastia * Mental state that precludes understanding of the protocol * Diagnosed, but untreated moderate or severe sleep apnea * Spinal nutrition screening tool score \>15 * Severe claustrophobia that precludes MRI testing * Current anticoagulant therapy * Use of any of the following pharmacologic agents in the previous 3 months (testosterone, leuprolide, androgenic hormones, growth hormone, oral androgen precursors, 5-alpha reductase or aromatase inhibitors) * Use of anti-resorptive or bone anabolic drug therapy in the previous 6 months * Known allergy to sesame oil

Design outcomes

Primary

Measure	Time frame	Description
Percent Change in Hip Bone Mineral Density	Baseline, 6 months, 12 months	Percent change in total hip bone mineral density of the non-dominant limb assessed via dual-energy X-ray absorptiometry (DXA)
Percent Changes in Muscle Cross-Sectional Area	Baseline, 6 months, 12 months	Percent Change in thigh (knee extensors) muscle cross-sectional area of the non-dominant limb assessed via MRI
Percent Change in Total Body Fat	Baseline, 6 months, 12 months	Percent change in total body fat assessed via dual-energy x-ray absorptiometry (DXA)
Absolute Change in Walking Speed	Baseline, 6 months, 12 months	Absolute change in 10 m walking speed

Secondary

Measure	Time frame	Description
Percent Change in Neuromuscular Function	Baseline, 6 months, 12 months	Percent change in thigh (knee extensors) peak isometric torque production of the non-dominant limb assessed via dynamometry
Percent Change in Visceral Fat	Baseline, 6 months, 12 months	Percent change in visceral (android) fat mass assessed via dual-energy x-ray absorptiometry (DXA)

Countries

United States

Participant flow

Recruitment details

Participants were recruited based on physician referrals at 2 VA medical centers and via community-based advertisements between January 2017 and March 2021 and pre-screened via phone to determine criteria to enroll. Those meeting criteria to enroll were screened for potential eligibility, with the first participant enrolled on April 27, 2017 and the last participant enrolled on December 4, 2020.

Pre-assignment details

Enrolled participants were evaluated at an in-person screening visit to determine if they qualify. Those that did not qualify were excluded from the study before randomization. Of 33 enrolled participants, 12 met inclusion criteria and were randomized to treatment / placebo groups.

Participants by arm

Arm	Count
Testosterone Enanthate, Finasteride Testosterone enanthate via i.m. injection (125 mg/week) and finasteride orally (5 mg/day) Testosterone Enanthate: Subjects receive testosterone (125 mg/week) by intramuscular injection Finasteride: Subjects receive finasteride (5 mg/day) orally	7
Placebo Treatment Placebo via i.m. injection (once weekly) and placebo pill orally (daily) Placebo injection: Subjects receive placebo (weekly) by intramuscular injection Placebo pill: Subjects receive placebo pill (daily) orally	5
Total	12

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	0
Overall Study	Physician Decision	0	1
Overall Study	VA mandated stop on all in person visits for VA sponsored research nationally	1	0
Overall Study	Withdrawal by Subject	2	1

Baseline characteristics

Characteristic	Placebo Treatment	Total	Testosterone Enanthate, Finasteride
Age, Continuous	57.4 years STANDARD_DEVIATION 9.4	60.5 years STANDARD_DEVIATION 7.8	62.7 years STANDARD_DEVIATION 6.3
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	2 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants	10 Participants	6 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Hip bone mineral density	1.016 g/cm^2 STANDARD_DEVIATION 0.1365	0.996 g/cm^2 STANDARD_DEVIATION 0.1712	0.9788 g/cm^2 STANDARD_DEVIATION 0.2073
Neuromuscular function	111 N/m STANDARD_DEVIATION 36	117 N/m STANDARD_DEVIATION 35	121 N/m STANDARD_DEVIATION 37
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	3 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	5 Participants	9 Participants	4 Participants
Region of Enrollment United States	5 participants	12 participants	7 participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	5 Participants	12 Participants	7 Participants
Thigh muscle cross-sectional area	6453 cm^2 STANDARD_DEVIATION 1177	7054 cm^2 STANDARD_DEVIATION 1783	7483 cm^2 STANDARD_DEVIATION 2096
Total body fat	30.3 kg STANDARD_DEVIATION 9.6	30.3 kg STANDARD_DEVIATION 8.6	30.4 kg STANDARD_DEVIATION 8.7
Visceral fat	3.19 kg STANDARD_DEVIATION 1.61	3.00 kg STANDARD_DEVIATION 1.25	2.85 kg STANDARD_DEVIATION 1
Walking speed	0.76 m/s STANDARD_DEVIATION 0.35	0.84 m/s STANDARD_DEVIATION 0.33	0.90 m/s STANDARD_DEVIATION 0.33

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 7	0 / 5
other Total, other adverse events	7 / 7	5 / 5
serious Total, serious adverse events	1 / 7	0 / 5