Search
Close this search box.

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

Studies

Study First Submitted Date 2021-04-08
Study First Posted Date 2021-04-30
Last Update Posted Date 2023-07-03
Start Month Year March 1, 2024
Primary Completion Month Year December 1, 2025
Verification Month Year June 2023
Verification Date 2023-06-30
Last Update Posted Date 2023-07-03

Facilities

Sequence: 199269151
Name VA Puget Sound Health Care System Seattle Division, Seattle, WA
City Seattle
State Washington
Zip 98108-1532
Country United States

Facility Contacts

Sequence: 28010728
Facility Id 199269151
Contact Type primary
Name Michael T Wininger, PhD
Email michael.wininger@va.gov
Phone 203-932-5711
Phone Extension 3262

Facility Investigators

Sequence: 18271664
Facility Id 199269151
Role Study Chair
Name Jose M. Garcia, MD PhD

Conditions

Sequence: 51975991 Sequence: 51975992
Name Adult Growth Hormone Deficiency Name Mild Traumatic Brain Injury
Downcase Name adult growth hormone deficiency Downcase Name mild traumatic brain injury

Id Information

Sequence: 40006727
Id Source org_study_id
Id Value 2018

Countries

Sequence: 42398836
Name United States
Removed False

Design Groups

Sequence: 55377437 Sequence: 55377438
Group Type Active Comparator Group Type Placebo Comparator
Title Growth Hormone Replacement Therapy Title Placebo
Description Recombinant Human Growth Hormone Description Placebo

Interventions

Sequence: 52287092 Sequence: 52287093
Intervention Type Drug Intervention Type Other
Name Somatropin Name Placebo
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. 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.

Design Outcomes

Sequence: 176684701 Sequence: 176684702 Sequence: 176684703 Sequence: 176684704 Sequence: 176684705 Sequence: 176684706 Sequence: 176684707
Outcome Type primary Outcome Type secondary Outcome Type other Outcome Type other Outcome Type other Outcome Type other Outcome Type other
Measure QoL-AGHDA (Quality of Life-Assessment of Adult Growth Hormone in Adults) Measure Body Composition Measure Depressive and Anxiety Symptoms measured by Depression Anxiety and Stress Scale (DASS-21) Measure Cognition Measure Severity of Fatigue Symptoms Measure Sleep Quality Measure Chronic Pain Assessment
Time Frame 6 months Time Frame 6 months Time Frame 6 months Time Frame 6 months Time Frame 6 months Time Frame 6 months Time Frame 6 months
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). 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. 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. 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. 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. 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. 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.

Browse Conditions

Sequence: 192714868 Sequence: 192714869 Sequence: 192714870 Sequence: 192714871 Sequence: 192714872 Sequence: 192714873 Sequence: 192714874 Sequence: 192714875 Sequence: 192714876 Sequence: 192714877 Sequence: 192714878 Sequence: 192714879 Sequence: 192714880 Sequence: 192714881 Sequence: 192714882 Sequence: 192714883 Sequence: 192714884 Sequence: 192714885 Sequence: 192714886 Sequence: 192714887 Sequence: 192714888
Mesh Term Dwarfism, Pituitary Mesh Term Brain Injuries Mesh Term Brain Injuries, Traumatic Mesh Term Brain Concussion Mesh Term Endocrine System Diseases Mesh Term Wounds and Injuries Mesh Term Brain Diseases Mesh Term Central Nervous System Diseases Mesh Term Nervous System Diseases Mesh Term Craniocerebral Trauma Mesh Term Trauma, Nervous System Mesh Term Dwarfism Mesh Term Bone Diseases, Developmental Mesh Term Bone Diseases Mesh Term Musculoskeletal Diseases Mesh Term Bone Diseases, Endocrine Mesh Term Hypopituitarism Mesh Term Pituitary Diseases Mesh Term Hypothalamic Diseases Mesh Term Head Injuries, Closed Mesh Term Wounds, Nonpenetrating
Downcase Mesh Term dwarfism, pituitary Downcase Mesh Term brain injuries Downcase Mesh Term brain injuries, traumatic Downcase Mesh Term brain concussion Downcase Mesh Term endocrine system diseases Downcase Mesh Term wounds and injuries Downcase Mesh Term brain diseases Downcase Mesh Term central nervous system diseases Downcase Mesh Term nervous system diseases Downcase Mesh Term craniocerebral trauma Downcase Mesh Term trauma, nervous system Downcase Mesh Term dwarfism Downcase Mesh Term bone diseases, developmental Downcase Mesh Term bone diseases Downcase Mesh Term musculoskeletal diseases Downcase Mesh Term bone diseases, endocrine Downcase Mesh Term hypopituitarism Downcase Mesh Term pituitary diseases Downcase Mesh Term hypothalamic diseases Downcase Mesh Term head injuries, closed Downcase Mesh Term wounds, nonpenetrating
Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor

Sponsors

Sequence: 48136383
Agency Class FED
Lead Or Collaborator lead
Name VA Office of Research and Development

Overall Officials

Sequence: 29173565
Role Study Chair
Name Jose M. Garcia, MD PhD
Affiliation VA Puget Sound Health Care System Seattle Division, Seattle, WA

Central Contacts

Sequence: 11964646 Sequence: 11964647
Contact Type primary Contact Type backup
Name Michael T Wininger, PhD Name Alexander Beed, MS
Phone (203) 932-5711 Phone (203) 932-5711
Email michael.wininger@va.gov Email Alexander.Beed@va.gov
Phone Extension 3262 Phone Extension 3799
Role Contact Role Contact

Design Group Interventions

Sequence: 67885449 Sequence: 67885450
Design Group Id 55377437 Design Group Id 55377438
Intervention Id 52287092 Intervention Id 52287093

Eligibilities

Sequence: 30650689
Gender All
Minimum Age 21 Years
Maximum Age 55 Years
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)
Adult True
Child False
Older Adult False

Calculated Values

Sequence: 254253638
Number Of Facilities 1
Registered In Calendar Year 2021
Were Results Reported False
Has Us Facility True
Has Single Facility True
Minimum Age Num 21
Maximum Age Num 55
Minimum Age Unit Years
Maximum Age Unit Years
Number Of Primary Outcomes To Measure 1
Number Of Secondary Outcomes To Measure 1
Number Of Other Outcomes To Measure 5

Designs

Sequence: 30397560
Allocation Randomized
Intervention Model Parallel Assignment
Observational Model
Primary Purpose Treatment
Time Perspective
Masking Quadruple
Intervention Model Description Two arm study: active drug vs placebo
Subject Masked True
Caregiver Masked True
Investigator Masked True
Outcomes Assessor Masked True

Responsible Parties

Sequence: 28764046
Responsible Party Type Sponsor