RECRUITING

Locomotor Training With Testosterone to Promote Bone and Muscle Health After Spinal Cord Injury

Conditions

Spinal Cord Injury Spinal Cord Injuries Trauma, Nervous System Wounds and Injury Central Nervous System Diseases Spinal Cord Diseases Gonadal Disorders Endocrine System Diseases Hypogonadism Genital Diseases, Male Spinal Cord Trauma Injuries, Spinal Cord Walking, Difficulty Gait Disorders, Neurologic Locomotion Disorder, Neurologic Wounds and Injuries Nervous System Diseases Testosterone Deficiency Androgen Deficiency Hormone Deficiency Testosterone Testosterone enanthate Testosterone undecanoate Testosterone 17 beta-cypionate Methyltestosterone Androgens Hormones Hormone Substitutes, and Hormone Antagonists Physiologic Effects of Drugs Pharmacologic Actions Therapeutic Uses Anabolic Agents Testosterone Replacement Therapy Dual Energy X ray Absorptiometry Lean Tissue Mass Body Composition Muscle Strength Muscle Mass Bone Mineral Density Adipose Tissue Body Fat Density, Bone Bone Formation Bone Resorption Bone Density Conservation Agents Magnetic Resonance Imaging Walking Ambulation Locomotor Locomotion Treadmill

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This pilot study will determine the feasibility of implementing a combinatory rehabilitation strategy involving testosterone replacement therapy (TRT) with locomotor training (LT; walking on a treadmill with assistance and overground walking) in men with testosterone deficiency and walking dysfunction after incomplete or complete spinal cord injury. The investigators hypothesize that LT+TRT treatment will improve muscle size and bone mineral density in men with low T and ambulatory dysfunction after incomplete or complete SCI, along with muscle fundtion and walking recovery in men with T low and ambulatory dysfunction ater incomplete SCI.

Official Title

Locomotor Training With Testosterone to Promote Bone and Muscle Health

Quick Facts

Study Start:2021-01-31

Study Completion:2025-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04460872

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Men \>18 years of age * Diagnosis of an incomplete SCI involving spinal segments L1 or above or a clinically complete SCI involving spinal segments T2-L1, with upper motor neuron injury signs (i.e., spasticity, hypertonicity) for \>60-days * Low serum total testosterone (\<300 ng/dL), bioavailable testosterone (\<110 ng/dL), or free testosterone (\<46 pg/mL or \<4.6 ng/dL) * Presence of one or more sign or symptom that may be related to low testosterone, including: loss of body hair or reduced shaving, very small testes (\<6 mL), reduced sexual desire (libido) and activity, decreased spontaneous erections (e.g., morning erections) or erectile dysfunction, breast discomfort or gynecomastia, height loss, low-trauma fracture, or low BMD, hot flushes or sweats, decreased energy, motivation, initiative, or self-confidence, fatigue or irritability, feeling sad or blue, having a depressed mood, or having a persistent low-grade depressive disorder, poor concentration or memory, sleep disturbances or increased sleepiness, mild unexplained anemia (normochromic or normocytic), reduced muscle bulk, strength, or physical performance, Increased body fat or body mass index, any other sign or symptom commonly associated with low testosterone * Locomotor dysfunction, definted as self-selected walking pace ≤1.0 m/s on a 10mWT, either with or without gait devices or braces and with or without assistance, or as self-selected walking pace \>1.0 m/s with reliance on a gait device or brace or with highly compensated movement impairments, as identified by a trained observer. * Diagnosis of first time SCI including etiology from trauma, vascular, or orthopedic pathology * Medically-stable condition that is asymptomatic for conditions that will interfere with the study participation * Willingness to administer TRT as instructed by the study staff and to abide by study protocol * Documented approval from the study physician verifying medical status	* Currently participating in another research protocol that may influence study outcomes. * Mental state that precludes understanding the study protocol. * Life expectancy \<12-months. * History of or current congenital SCI (e.g., Chiari malformation, myelomeningocele, intraspinal neoplasm, Frederich's ataxis) or other degenerative spinal disorder (e.g., spinocerebellar degeneration) that may complicate study procedures * Multiple sclerosis, amyotrophic lateral sclerosis, or other neurologic impairment or injury * Current prostate, breast, or other organ cancer or a history of prostate or breast cancer * Any other diagnosed or treated cancer within the past 24-months, with the exceptions of basal or squamous cell carcinoma of the skin that has been successfully treated * Serum prostate-specific antigen (PSA) \>3.0 ng/mL \[men treated with 5-alpha reductase inhibitors (e.g., finasteride or dutasteride) are eligible to participate if PSA values are ≤1.5 ng/mL\] * Prostate nodule or induration noted on digital rectal exam (DRE) during screening that tests positive for prostate cancer * Currently seeking fertility or expected during the duration of the study * Gynecomastia * Hematocrit (HCT) \>49% * Any major cardiovascular (CV) 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, revascularization of the carotid or middle cerebral artery or procedures to treat critical limb ischemia, or hospitalization due to unstable angina, transient ischemic attack, stroke, or peripheral vascular disease) * Angina that is not controlled on a current medical regimen (Canadian class II, III, or IV) * Poorly compensated congestive heart failure (NYHA class III or IV) * Poorly controlled hypertension (consistently measured systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg), while on medications * Poorly controlled arrhythmia of any type * Severe valvular heart disease * Baseline electrocardiogram (ECG) findings such as left bundle branch block or marked ECG abnormalities that would preclude serial screening evaluations for occult ischemic events * History of unprovoked deep venous thrombosis (DVT), unprovoked pulmonary embolism, history of recurrent DVT or known thrombophilia * LDL cholesterol \>160 mg/dL with history of any major CV event, defined above, within the last 12-months * Major non-CV surgery (e.g., major abdominal or thoracic procedure) within 90-days prior to screening and/or a major surgery scheduled at the time of screening * Liver enzymes (AST or ALT) \>1.5 times the normal upper limit * Severe or end-stage chronic kidney disease documented by estimated glomerular filtration rate (eGFR) \<30 mL/min * Diagnosed, but untreated severe obstructive sleep apnea * Lower extremity fracture in the last 12-months (exclusion criterion for participation in LT+TRT group only) * Femoral neck, total hip, or lumbar spine t-score below -2.5 or distal femur BMD \<0.70 g/cm2, assessed via DEXA at screening (exclusion criterion for participation in LT+TRT group only) * Current anticoagulant therapy (contraindication for i.m. injections) * Use of any of the following pharmacologic agents in the previous 90-days: any TRT formulation, any compounded or over-the-counter androgenic hormones or androgen precursors, clomiphene, aromatase inhibitors, anti-estrogen or estrogen treatment, or growth hormone * Use of anti-resorptive or bone anabolic drug therapy in the previous 180-days * Acute use (\>5-days) of any opioids (e.g., oxycodone, hydrocodone, etc) or systemic glucocorticoids \>7.5 mg/d prednisone equivalent (e.g., hydrocortisone 30 mg, methylprednisolone 6 mg, or dexamethasone 1.2 mg) within 1-week before screening visit, except men who are taking these medications for a chronic condition and are anticipated to continue treatment for the study duration * Known allergy to any component of the TRT formulation (e.g., sesame oil or cottonseed oil) * Any other condition, therapy, lab abnormality, medical or psychiatric conditions, or reason that might pose a risk to the participant, make participation not in the person's best interest, confound the study results (e.g., inability to comply with study requirements), make the participant unsuitable to receive study intervention, or interfere with the person's ability to participate for the entire study duration

Inclusion Criteria

Exclusion Criteria

* Men \>18 years of age
* Diagnosis of an incomplete SCI involving spinal segments L1 or above or a clinically complete SCI involving spinal segments T2-L1, with upper motor neuron injury signs (i.e., spasticity, hypertonicity) for \>60-days
* Low serum total testosterone (\<300 ng/dL), bioavailable testosterone (\<110 ng/dL), or free testosterone (\<46 pg/mL or \<4.6 ng/dL)
* Presence of one or more sign or symptom that may be related to low testosterone, including: loss of body hair or reduced shaving, very small testes (\<6 mL), reduced sexual desire (libido) and activity, decreased spontaneous erections (e.g., morning erections) or erectile dysfunction, breast discomfort or gynecomastia, height loss, low-trauma fracture, or low BMD, hot flushes or sweats, decreased energy, motivation, initiative, or self-confidence, fatigue or irritability, feeling sad or blue, having a depressed mood, or having a persistent low-grade depressive disorder, poor concentration or memory, sleep disturbances or increased sleepiness, mild unexplained anemia (normochromic or normocytic), reduced muscle bulk, strength, or physical performance, Increased body fat or body mass index, any other sign or symptom commonly associated with low testosterone
* Locomotor dysfunction, definted as self-selected walking pace ≤1.0 m/s on a 10mWT, either with or without gait devices or braces and with or without assistance, or as self-selected walking pace \>1.0 m/s with reliance on a gait device or brace or with highly compensated movement impairments, as identified by a trained observer.
* Diagnosis of first time SCI including etiology from trauma, vascular, or orthopedic pathology
* Medically-stable condition that is asymptomatic for conditions that will interfere with the study participation
* Willingness to administer TRT as instructed by the study staff and to abide by study protocol
* Documented approval from the study physician verifying medical status

* Currently participating in another research protocol that may influence study outcomes.
* Mental state that precludes understanding the study protocol.
* Life expectancy \<12-months.
* History of or current congenital SCI (e.g., Chiari malformation, myelomeningocele, intraspinal neoplasm, Frederich's ataxis) or other degenerative spinal disorder (e.g., spinocerebellar degeneration) that may complicate study procedures
* Multiple sclerosis, amyotrophic lateral sclerosis, or other neurologic impairment or injury
* Current prostate, breast, or other organ cancer or a history of prostate or breast cancer
* Any other diagnosed or treated cancer within the past 24-months, with the exceptions of basal or squamous cell carcinoma of the skin that has been successfully treated
* Serum prostate-specific antigen (PSA) \>3.0 ng/mL \[men treated with 5-alpha reductase inhibitors (e.g., finasteride or dutasteride) are eligible to participate if PSA values are ≤1.5 ng/mL\]
* Prostate nodule or induration noted on digital rectal exam (DRE) during screening that tests positive for prostate cancer
* Currently seeking fertility or expected during the duration of the study
* Gynecomastia
* Hematocrit (HCT) \>49%
* Any major cardiovascular (CV) 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, revascularization of the carotid or middle cerebral artery or procedures to treat critical limb ischemia, or hospitalization due to unstable angina, transient ischemic attack, stroke, or peripheral vascular disease)
* Angina that is not controlled on a current medical regimen (Canadian class II, III, or IV)
* Poorly compensated congestive heart failure (NYHA class III or IV)
* Poorly controlled hypertension (consistently measured systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg), while on medications
* Poorly controlled arrhythmia of any type
* Severe valvular heart disease
* Baseline electrocardiogram (ECG) findings such as left bundle branch block or marked ECG abnormalities that would preclude serial screening evaluations for occult ischemic events
* History of unprovoked deep venous thrombosis (DVT), unprovoked pulmonary embolism, history of recurrent DVT or known thrombophilia
* LDL cholesterol \>160 mg/dL with history of any major CV event, defined above, within the last 12-months
* Major non-CV surgery (e.g., major abdominal or thoracic procedure) within 90-days prior to screening and/or a major surgery scheduled at the time of screening
* Liver enzymes (AST or ALT) \>1.5 times the normal upper limit
* Severe or end-stage chronic kidney disease documented by estimated glomerular filtration rate (eGFR) \<30 mL/min
* Diagnosed, but untreated severe obstructive sleep apnea
* Lower extremity fracture in the last 12-months (exclusion criterion for participation in LT+TRT group only)
* Femoral neck, total hip, or lumbar spine t-score below -2.5 or distal femur BMD \<0.70 g/cm2, assessed via DEXA at screening (exclusion criterion for participation in LT+TRT group only)
* Current anticoagulant therapy (contraindication for i.m. injections)
* Use of any of the following pharmacologic agents in the previous 90-days: any TRT formulation, any compounded or over-the-counter androgenic hormones or androgen precursors, clomiphene, aromatase inhibitors, anti-estrogen or estrogen treatment, or growth hormone
* Use of anti-resorptive or bone anabolic drug therapy in the previous 180-days
* Acute use (\>5-days) of any opioids (e.g., oxycodone, hydrocodone, etc) or systemic glucocorticoids \>7.5 mg/d prednisone equivalent (e.g., hydrocortisone 30 mg, methylprednisolone 6 mg, or dexamethasone 1.2 mg) within 1-week before screening visit, except men who are taking these medications for a chronic condition and are anticipated to continue treatment for the study duration
* Known allergy to any component of the TRT formulation (e.g., sesame oil or cottonseed oil)
* Any other condition, therapy, lab abnormality, medical or psychiatric conditions, or reason that might pose a risk to the participant, make participation not in the person's best interest, confound the study results (e.g., inability to comply with study requirements), make the participant unsuitable to receive study intervention, or interfere with the person's ability to participate for the entire study duration

Contacts and Locations

Study Contact

Joshua F Yarrow, PhD

CONTACT

(352) 548-6477

joshua.yarrow@va.gov

Dana M Otzel, PhD

CONTACT

(352) 548-6477

dana.otzel@va.gov

Principal Investigator

Joshua F Yarrow, PhD

STUDY_DIRECTOR

North Florida/South Georgia Veterans Health System

Dana M Otzel, Phd

PRINCIPAL_INVESTIGATOR

North Florida/South Georgia Veterans Health System

Study Locations (Sites)

North Florida/South Georgia Veterans Health System

Gainesville, Florida, 32608

United States

Brooks Rehabilitation

Jacksonville, Florida, 32216

United States

Collaborators and Investigators

Sponsor: North Florida Foundation for Research and Education

Joshua F Yarrow, PhD, STUDY_DIRECTOR, North Florida/South Georgia Veterans Health System
Dana M Otzel, Phd, PRINCIPAL_INVESTIGATOR, North Florida/South Georgia Veterans Health System

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-01-31

Study Completion Date2025-06-30

Study Record Updates

Study Start Date2021-01-31

Study Completion Date2025-06-30

Terms related to this study

Keywords Provided by Researchers

Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Androgens
Hormones
Hormone Substitutes, and Hormone Antagonists
Physiologic Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Anabolic Agents
Testosterone Replacement Therapy
Dual Energy X ray Absorptiometry
Lean Tissue Mass
Body Composition
Muscle Strength
Muscle Mass
Bone Mineral Density
Adipose Tissue
Body Fat
Density, Bone
Bone Formation
Bone Resorption
Bone Density Conservation Agents
Magnetic Resonance Imaging
Walking
Ambulation
Locomotor
Locomotion
Treadmill
Spinal Cord Injury

Additional Relevant MeSH Terms

Spinal Cord Injury
Spinal Cord Injuries
Trauma, Nervous System
Wounds and Injury
Central Nervous System Diseases
Spinal Cord Diseases
Gonadal Disorders
Endocrine System Diseases
Hypogonadism
Genital Diseases, Male
Spinal Cord Trauma
Injuries, Spinal Cord
Walking, Difficulty
Gait Disorders, Neurologic
Locomotion Disorder, Neurologic
Wounds and Injuries
Nervous System Diseases
Testosterone Deficiency
Androgen Deficiency
Hormone Deficiency