Growth Hormone Replacement Therapy in Veterans With Mild Traumatic Brain Injury (mTBI) and Adult Growth Hormone Deficiency (AGHD)

NCT04867317 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 2018
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to determine whether growth hormone replacement therapy (GHRT) is effective versus placebo in the improvement of Quality of Life in patients with adult growth hormone deficiency (AGHD) and mild traumatic brain injury (mTBI).

Conditions

Adult Growth Hormone Deficiency; Mild Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• QoL-AGHDA (Quality of Life-Assessment of Adult Growth Hormone in Adults)

  25 question survey on quality of life; The primary objective of CSP #2018 is to determine the efficacy of rhGH, given daily for 6 months, versus placebo to improve QoL, as measured by difference in mean QoL-AGHDA score, among Veterans with a history of mTBI and AGHD (primary outcome). The primary hypothesis is that the investigators, compared to placebo, patients treated with rhGH will exhibit a 3.5-point lower mean score (higher quality of life) in QoL-AGHDA at 6 months. QoL-AGHDA: minimum score=0 (high QoL: best outcome); maximum score=25 (low QoL: worst outcome).

  6 months

Secondary Outcomes (1)

• Body Composition

  6 months

Other Outcomes (5)

• Depressive and Anxiety Symptoms measured by Depression Anxiety and Stress Scale (DASS-21)

  6 months

• Cognition

  6 months

• Severity of Fatigue Symptoms

  6 months

Study Arms (2)

Growth Hormone Replacement Therapy

ACTIVE COMPARATOR

Recombinant Human Growth Hormone

Drug: Somatropin

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

Somatropin DRUG

Participants (n=172) will be randomized in a 1:1 ratio to rhGH (n=86) versus placebo (n=86) for six months, stratified by participating site. Both study participants and the study team will be blinded to treatment assignment. All participants will complete in-clinic follow-ups at Days 14, 40, 65, and 90 (3 months) and at day 180 (6 months). The primary outcome will be the mean difference in QoL-AGHDA scores between treatment arms at 6 months follow-up. Patients will discontinue the study intervention at 6 months, and will be followed-up two weeks subsequent, in order to assure patient safety and wellness, and to ensure maximal facilitation of patient transition back into routine care.

Growth Hormone Replacement Therapy

Placebo OTHER

Participants (n=172) will be randomized in a 1:1 ratio to rhGH (n=86) versus placebo (n=86) for six months, stratified by participating site. Both study participants and the study team will be blinded to treatment assignment. All participants will complete in-clinic follow-ups at Days 14, 40, 65, and 90 (3 months) and at day 180 (6 months). The primary outcome will be the mean difference in QoL-AGHDA scores between treatment arms at 6 months follow-up. Patients will discontinue the study intervention at 6 months, and will be followed-up two weeks subsequent, in order to assure patient safety and wellness, and to ensure maximal facilitation of patient transition back into routine care.

Placebo

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• OEF/OIF/OND Veteran
• Score of 18 or more on Combat Experiences sub-scale of Deployment Risk and Resilience Inventory-2 (DRRI-2)
• Age 21 - 55 years old
• One or more mTBI sustained during military service at least 12 months prior to the screening date, as noted via the CRAFT survey.
• GH deficiency diagnosed by: macimorelin stimulation test (cut point 5.1 mcg/L) and IGF-I lab values have to be less than or equal to +1 SDS at baseline
• Score of 11 or more on QoL-AGHDA
• week stability on any psychotropic medications
• month stability on all other hormone treatments
• Able and willing to provide informed consent to participate in this study, and complete study protocol.

You may not qualify if:

• History of moderate or severe TBI
• History of neurologic disorder other than TBI with substantial impact on quality of life
• History of bipolar disorder, schizophrenia, or other concurrent psychotic disorder
• Active suicidal ideation (no plan required) as determined by a score of 2 points or more on the Columbia Suicide Severity Rating Scale (C-SSRS) suicidal ideation rating, or overt suicidal behavior in the past 6 months
• Contraindication to rhGH therapy
• Contraindication to macimorelin use, including QTc interval \>470ms
• Acute medical illness, active infection, cancer or decompensated chronic medical illness
• Evidence of substance use disorder, -other than mild alcohol or cannabis use disorder-, or urine toxicology evidence of the use of an illicit drug (excluding cannabis), in the past 6 months. Nicotine use is allowed.
• Score less than or equal to 41 on Trial 2 or Retention Trial of the Test of Memory Malingering (TOMM).
• BMI \> 35 or body weight \> 350 lbs
• Pituitary anatomy documented by an MRI using a sella protocol within the last 2 years indicating abnormalities consistent with an etiology other than mild-TBI (i.e.; pituitary mass)
• Women who are pregnant or of child-bearing potential not on contraception
• Current use of the following: growth hormone, estrogen or estrogen-like dietary supplements, progestin, IGF-I, or chronic glucocorticoid use in supraphysiologic doses
• Currently enrolled in any other interventional study unless prior approval is provided by the study chairs and the study sponsor (Cooperative Studies Program)

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (4)

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033-4004, United States

RECRUITING

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, 55417-2309, United States

RECRUITING

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030-4211, United States

RECRUITING

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, 98108-1532, United States

RECRUITING

MeSH Terms

Conditions

Dwarfism, Pituitary; Brain Concussion

Interventions

Human Growth Hormone

Condition Hierarchy (Ancestors)

Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Endocrine; Hypopituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Brain Injuries, Traumatic; Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating

Intervention Hierarchy (Ancestors)

Growth Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Jose M. Garcia, MD PhD

  VA Puget Sound Health Care System Seattle Division, Seattle, WA

  STUDY CHAIR

Central Study Contacts

Deane V Walker, MHA BS AB

CONTACT

(203) 937-3440; Deane.Walker@va.gov

Michael T Wininger, PhD

CONTACT

(203) 932-5711; michael.wininger@va.gov

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Two arm study: active drug vs placebo

Study Record Dates

• First Submitted: April 8, 2021
• First Posted: April 30, 2021
• Study Start: January 13, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): September 30, 2029
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (4)