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

May 14, 2026 updated by: VA Office of Research and Development

CSP #2018 - Growth Hormone Replacement Therapy in Veterans With Mild Traumatic Brain Injury (mTBI) and Adult Growth Hormone Deficiency (AGHD)

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

172

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233-1927
    • Arizona
      • Phoenix, Arizona, United States, 85012
    • California
      • Palo Alto, California, United States, 94304-1207
        • Not yet recruiting
        • VA Palo Alto Health Care System, Palo Alto, CA
        • Contact:
          • TBD TBD
          • Phone Number: 000-000-0000
        • Contact:
          • TBD TBD, MD
          • Phone Number: 0000000000
      • San Diego, California, United States, 92161-0002
    • Colorado
      • Aurora, Colorado, United States, 80045-7211
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20422-0001
        • Not yet recruiting
        • Washington DC VA Medical Center, Washington, DC
        • Contact:
    • Georgia
      • Decatur, Georgia, United States, 30033-4004
        • Active, not recruiting
        • Atlanta VA Medical and Rehab Center, Decatur, GA
    • Michigan
      • Ann Arbor, Michigan, United States, 48105-2303
    • Minnesota
      • Minneapolis, Minnesota, United States, 55417-2309
        • Recruiting
        • Minneapolis VA Health Care System, Minneapolis, MN
        • Contact:
        • Contact:
    • Missouri
      • Kansas City, Missouri, United States, 64128-2226
    • Nebraska
      • Omaha, Nebraska, United States, 68105-1850
    • North Carolina
      • Salisbury, North Carolina, United States, 28144
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104-5007
    • Texas
      • Dallas, Texas, United States, 75216-7167
        • Not yet recruiting
        • VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
        • Contact:
        • Contact:
      • Houston, Texas, United States, 77030-4211
        • Recruiting
        • Michael E. DeBakey VA Medical Center, Houston, TX
        • Contact:
        • Contact:
      • San Antonio, Texas, United States, 78229-4404
    • Washington
      • Seattle, Washington, United States, 98108-1532
        • Recruiting
        • VA Puget Sound Health Care System Seattle Division, Seattle, WA
        • Study Chair:
          • Jose M. Garcia, MD PhD
        • Contact:
        • Contact:

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.

Eligibility Criteria

Ages Eligible for Study

21 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. OEF/OIF/OND Veteran
  2. Score of 18 or more on Combat Experiences sub-scale of Deployment Risk and Resilience Inventory-2 (DRRI-2)
  3. Age 21 - 55 years old
  4. One or more mTBI sustained during military service at least 12 months prior to the screening date, as noted via the CRAFT survey.
  5. GH deficiency diagnosed by: macimorelin stimulation test (cut point 5.1 mcg/L), or glucagon stimulation test (cut point: 3 mcg/L for BMI up to 25; cut point 1 mcg/L for BMI 25 and above) and IGF-I lab values have to be less than or equal to +1 SDS at baseline
  6. Score of 11 or more on QoL-AGHDA
  7. 4-week stability on any psychotropic medications
  8. 3-month stability on all other hormone treatments
  9. Able and willing to provide informed consent to participate in this study, and complete study protocol.

Exclusion Criteria:

  1. History of moderate or severe TBI
  2. History of neurologic disorder other than TBI with substantial impact on quality of life
  3. History of bipolar disorder, schizophrenia, or other concurrent psychotic disorder
  4. 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.
  5. Contraindication to rhGH therapy
  6. Acute medical illness, active infection, cancer or decompensated chronic medical illness
  7. 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.
  8. Score less than or equal to 41 on Trial 2 or Retention Trial of the Test of Memory and Malingering (TOMM).
  9. BMI > 40 or body weight > 350 lbs
  10. 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)
  11. Women who are pregnant or of child-bearing potential not on contraception
  12. Current use of the following: growth hormone, estrogen or estrogen-like dietary supplements, progestin, IGF-I, or chronic glucocorticoid use in supraphysiologic doses
  13. Currently enrolled in any other interventional study unless prior approval is provided by the study chairs and the study sponsor (Cooperative Studies Program)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Other: Placebo
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.
Active Comparator: Growth Hormone Replacement Therapy
Recombinant Human Growth Hormone
Drug: Somatropin
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
QoL-AGHDA (Quality of Life-Assessment of Adult Growth Hormone in Adults)
Time Frame: 6 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Body Composition
Time Frame: 6 months
DEXA (Dual-Energy x-ray absorptiometry); The secondary objective of CSP #2018 is to investigate the efficacy of rhGH vs placebo on long-term surrogate outcomes: a) body composition, assessed through dual-energy x-ray absorptiometry (DEXA) and b) cardiometabolic risk factors including lipids, autonomic function, and highly sensitive C-reactive protein. The specific hypotheses for these outcomes are that compared to placebo there will be a 4.5% mean reduction in total truncal body fat percentage and a mean reduction of 10 mg/dL in LDL serum levels after 6 months of treatment and follow-up of rhGH.
6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Severity of Fatigue Symptoms
Time Frame: 6 months
Tertiary endpoint of interest: Severity of fatigue symptoms measured by the Patient Health Questionnaire 15-item somatic symptom severity scale PHQ-15 are expected to improve after 6 months of rhGH therapy compared to the placebo arm.
6 months
Sleep Quality
Time Frame: 6 months
Exploratory objective and hypothesis: Sleep quality as measured by the Pittsburgh Sleep Quality Index Score (PSQI). We hypothesize that subjective measures of sleep quality and daytime sleepiness will significantly improve in the active arm compared to placebo.
6 months
Chronic Pain Assessment
Time Frame: 6 months
Exploratory objective and hypothesis: Chronic pain assessed using the Defense Veterans Pain Report System-II (DVPRS-II); hypothesize that pain severity and pain interference with activities of daily living will be significantly reduced among participants receiving GHRT compared to placebo.
6 months
Cognition
Time Frame: 6 months
Tertiary endpoint of interest: Cognitive functioning will be assessed the Color Word Interference Test for cognitive flexibility and inhibition; the Digit Span test for working memory capacity; the Trail Making Test for processing speed, cognitive flexibility, and attention; the Grooved Pegboard for fine motor control and coordination; the Letter Fluency Test for verbal fluency and executive function; and the Rey Auditory Verbal Learning Test for verbal learning, memory, and attention. All test scores will be converted to z-scores, which standardize the results based on the mean and standard deviation of the normative sample, then averaged to generate a composite score, with higher scores indicating better performance relative to the normative sample. Both, individual test scores and the composite score will be analyzed to evaluate whether six-month recombinant human Growth Hormone treatment has any significant effect on cognitive performance.
6 months
Depressive and Anxiety Symptoms measured by Depression Anxiety and Stress Scale (DASS-21)
Time Frame: 6 months
Tertiary endpoint of interest: Depressive and anxiety symptoms measured by DASS-21 scores and post-traumatic stress symptoms measured by the PTSD Checklist for DSM-5 are expected to be lower (improved) within the rhGH arm after 6 months of therapy compared to the placebo arm.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Investigators

  • Study Chair: Jose M. Garcia, MD PhD, VA Puget Sound Health Care System Seattle Division, Seattle, WA

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 Major Dates

Study Start (Actual)

January 13, 2025

Primary Completion (Estimated)

February 28, 2027

Study Completion (Estimated)

September 30, 2029

Study Registration Dates

First Submitted

April 8, 2021

First Submitted That Met QC Criteria

April 28, 2021

First Posted (Actual)

April 30, 2021

Study Record Updates

Last Update Posted (Actual)

May 15, 2026

Last Update Submitted That Met QC Criteria

May 14, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Digital data underlying primary scientific publications from this study will be held as part of a data sharing resource maintained by the Cooperative Studies Program (VA-CSP). These data may be available to the public and other VA and non-VA researchers under certain conditions and consistent with the informed consent and CSP policy which prioritize protecting subjects' privacy and confidentiality to the fullest extent possible.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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