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

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: Not yet recruiting
• Conditions: Mild Traumatic Brain Injury; Adult Growth Hormone Deficiency
• Intervention / Treatment: Drug: Somatropin; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 172
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Alexander Beed, MS; Phone Number: 3799 (203) 932-5711; Email: Alexander.Beed@va.gov
• Study Contact Backup: Name: Michael T Wininger, PhD; Phone Number: 3262 (203) 932-5711; Email: michael.wininger@va.gov

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98108-1532
      • VA Puget Sound Health Care System Seattle Division, Seattle, WA
      • Contact: Michael T Wininger, PhD; Phone Number: 3262 203-932-5711; Email: michael.wininger@va.gov
      • Study Chair: Jose M. Garcia, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• OEF/OIF/OND Veteran
• Score of 1 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 IGFI lab values have to be less than or equal to +1 SDS at baseline
• Score of 11 or more on QoL-AGHDA
• 4-week stability on any psychotropic medications
• 3-month stability on all other hormone treatments
• Able and willing to provide informed consent to participate in this study, and complete study protocol.

Exclusion Criteria:

• 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 >450ms (male) or >470ms (female)
• 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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

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)	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, 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	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
Depressive and Anxiety Symptoms measured by Depression Anxiety and Stress Scale (DASS-21)	Tertiary endpoint of interest: Depressive and anxiety symptoms measured by DESS-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
Cognition	Tertiary endpoint of interest: Cognition will be measured by the NIH Toolbox Fluid Cognition Composite Score (NIHTB-FCCS), which is comprised on tests that measure executive function, inhibition, processing speed, and episodic memory. It is expected that this composite score will be higher (improve) within the rhGH arm after 6 months of therapy compared to the placebo arm.	6 months
Severity of Fatigue Symptoms	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	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	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

Collaborators and Investigators

• 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

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): March 1, 2028

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): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Musculoskeletal Diseases; Craniocerebral Trauma; Trauma, Nervous System; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Pituitary Diseases; Dwarfism; Bone Diseases, Developmental; Hypopituitarism; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Dwarfism, Pituitary; Endocrine System Diseases; Brain Concussion
• 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