search
Back to results

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

Primary Purpose

Adult Growth Hormone Deficiency, Mild Traumatic Brain Injury

Status
Not yet recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Somatropin
Placebo
Sponsored by
VA Office of Research and Development
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Growth Hormone Deficiency

Eligibility Criteria

21 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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)
  • One or more TBI on Military-specific sub-domains of Boston Assessment of Traumatic Brain Injury-Lifetime (BAT-L)
  • GH deficiency diagnosed by: macimorelin stimulation test (cut point 5.1 mcg/L)
  • 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 bi-polar 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 Scale (C-SSRS) suicidal ideation rating, or overt suicidal behavior in the past 6 months Contraindication to rhGH therapy
  • Contraindication to macimorelin use
  • Acute medical illness, active infection, cancer or decompensated chronic medical illness
  • Evidence of substance abuse disorder in the past 6 months other than mild alcohol or cannabis use disorder; nicotine use is allowed
  • Urine toxicology evidence of the use of an illicit drug, excluding cannabis, within the past 90 days prior to screening
  • Scoring less than 41 on Trial I of the Test of Memory and Malingering (TOMM) BMI >35 or body weight >350 lbs

  • Pituitary anatomy documented by an MRI using a sella protocol within the past 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, IGH-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)

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Growth Hormone Replacement Therapy

Placebo

Arm Description

Recombinant Human Growth Hormone

Placebo

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

Full Information

First Posted
April 8, 2021
Last Updated
June 29, 2023
Sponsor
VA Office of Research and Development
search

1. Study Identification

Unique Protocol Identification Number
NCT04867317
Brief Title
Growth Hormone Replacement Therapy in Veterans With Mild Traumatic Brain Injury (mTBI) and Adult Growth Hormone Deficiency (AGHD)
Acronym
GRIT
Official Title
CSP #2018 - Growth Hormone Replacement Therapy in Veterans With Mild Traumatic Brain Injury (mTBI) and Adult Growth Hormone Deficiency (AGHD)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 1, 2024 (Anticipated)
Primary Completion Date
December 1, 2025 (Anticipated)
Study Completion Date
December 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Growth Hormone Deficiency, Mild Traumatic Brain Injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Two arm study: active drug vs placebo
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
172 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Growth Hormone Replacement Therapy
Arm Type
Active Comparator
Arm Description
Recombinant Human Growth Hormone
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Somatropin
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
QoL-AGHDA (Quality of Life-Assessment of Adult Growth Hormone in Adults)
Description
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).
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Body Composition
Description
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.
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Depressive and Anxiety Symptoms measured by Depression Anxiety and Stress Scale (DASS-21)
Description
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.
Time Frame
6 months
Title
Cognition
Description
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.
Time Frame
6 months
Title
Severity of Fatigue Symptoms
Description
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.
Time Frame
6 months
Title
Sleep Quality
Description
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.
Time Frame
6 months
Title
Chronic Pain Assessment
Description
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.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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) One or more TBI on Military-specific sub-domains of Boston Assessment of Traumatic Brain Injury-Lifetime (BAT-L) GH deficiency diagnosed by: macimorelin stimulation test (cut point 5.1 mcg/L) 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 bi-polar 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 Scale (C-SSRS) suicidal ideation rating, or overt suicidal behavior in the past 6 months Contraindication to rhGH therapy Contraindication to macimorelin use Acute medical illness, active infection, cancer or decompensated chronic medical illness Evidence of substance abuse disorder in the past 6 months other than mild alcohol or cannabis use disorder; nicotine use is allowed Urine toxicology evidence of the use of an illicit drug, excluding cannabis, within the past 90 days prior to screening Scoring less than 41 on Trial I of the Test of Memory and Malingering (TOMM) BMI >35 or body weight >350 lbs Pituitary anatomy documented by an MRI using a sella protocol within the past 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, IGH-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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michael T Wininger, PhD
Phone
(203) 932-5711
Ext
3262
Email
michael.wininger@va.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Alexander Beed, MS
Phone
(203) 932-5711
Ext
3799
Email
Alexander.Beed@va.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jose M. Garcia, MD PhD
Organizational Affiliation
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Official's Role
Study Chair
Facility Information:
Facility Name
VA Puget Sound Health Care System Seattle Division, Seattle, WA
City
Seattle
State/Province
Washington
ZIP/Postal Code
98108-1532
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael T Wininger, PhD
Phone
203-932-5711
Ext
3262
Email
michael.wininger@va.gov
First Name & Middle Initial & Last Name & Degree
Jose M. Garcia, MD PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

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

We'll reach out to this number within 24 hrs