Clinical trial NCT04867317: Growth Hormone Replacement Therapy in Veterans With Mild Traumatic Brain Injury (mTBI) and Adult Growth Hormone Deficiency (AGHD)
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
Overall status: RECRUITING
Phase: PHASE3
Conditions: Adult Growth Hormone Deficiency
Mild Traumatic Brain Injury
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2021-04-30
Enrollment: 172
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two arm study: active drug vs placebo
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* OEF/OIF/OND Veteran
* Score of 18 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 IGF-I 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 \>470ms
* 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)

Primary outcomes:
measure: QoL-AGHDA (Quality of Life-Assessment of Adult Growth Hormone in Adults)
timeFrame: 6 months
Secondary outcomes:
measure: Body Composition
timeFrame: 6 months
Other outcomes:
measure: Depressive and Anxiety Symptoms measured by Depression Anxiety and Stress Scale (DASS-21)
timeFrame: 6 months
measure: Cognition
timeFrame: 6 months
measure: Severity of Fatigue Symptoms
timeFrame: 6 months
measure: Sleep Quality
timeFrame: 6 months
measure: Chronic Pain Assessment
timeFrame: 6 months
Locations:
city: Miami
country: United States
facility: Miami VA Healthcare System, Miami, FL
state: Florida
city: Decatur
country: United States
facility: Atlanta VA Medical and Rehab Center, Decatur, GA
state: Georgia
city: Minneapolis
country: United States
facility: Minneapolis VA Health Care System, Minneapolis, MN
state: Minnesota
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center, Houston, TX
state: Texas
city: Seattle
country: United States
facility: VA Puget Sound Health Care System Seattle Division, Seattle, WA
state: Washington
Study officials:
affiliation: VA Puget Sound Health Care System Seattle Division, Seattle, WA
name: Jose M. Garcia, MD PhD
role: STUDY_CHAIR
References: