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AGH Replacement Therapy With mTBI (GRIT)

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ClinicalTrials.gov Identifier: NCT04867317
Recruitment Status : Not yet recruiting
First Posted : April 30, 2021
Last Update Posted : April 30, 2021
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

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).

Condition or disease Intervention/treatment Phase
Adult Growth Hormone Deficiency Mild Traumatic Brain Injury Drug: Macimorelin Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 172 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Two arm study: active drug vs placebo
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: CSP #2018 - Growth Hormone Replacement Therapy in Veterans With Mild Traumatic Brain Injury (mTBI) and Adult Growth Hormone Deficiency (AGHD)
Estimated Study Start Date : October 1, 2021
Estimated Primary Completion Date : September 30, 2024
Estimated Study Completion Date : September 30, 2025


Arm Intervention/treatment
Active Comparator: Growth Hormone Replacement Therapy
Recombinant Human Growth Hormone
Drug: Macimorelin
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.
Other Name: Macrilen

Placebo Comparator: Placebo
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.




Primary Outcome Measures :
  1. 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, 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 :
  1. 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.


Other Outcome Measures:
  1. 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 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.

  2. Cognition [ Time Frame: 6 months ]
    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.

  3. 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.

  4. 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.

  5. 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.



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Ages Eligible for Study:   21 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04867317


Contacts
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Contact: Michael T Wininger, PhD (203) 932-5711 ext 3262 michael.wininger@va.gov
Contact: Alexander Beed, MS (203) 932-5711 ext 3799 Alexander.Beed@va.gov

Locations
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United States, Washington
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Seattle, Washington, United States, 98108
Contact: Michael T Wininger, PhD    203-932-5711 ext 3262    michael.wininger@va.gov   
Study Chair: Jose M. Garcia, MD PhD         
Sponsors and Collaborators
VA Office of Research and Development
Investigators
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Study Chair: Jose M. Garcia, MD PhD VA Puget Sound Health Care System Seattle Division, Seattle, WA
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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT04867317    
Other Study ID Numbers: 2018
First Posted: April 30, 2021    Key Record Dates
Last Update Posted: April 30, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

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