Adult Growth Hormone Deficiency, Mild Traumatic Brain Injury
Conditions
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).
Interventions
DRUGSomatropin
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.
OTHERPlacebo
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.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Two arm study: active drug vs placebo
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. OEF/OIF/OND Veteran 2. Score of 18 or more on Combat Experiences sub-scale of Deployment Risk and Resilience Inventory-2 (DRRI-2) 3. Age 21 - 55 years old 4. One or more mTBI sustained during military service at least 12 months prior to the screening date, as noted via the CRAFT survey. 5. GH deficiency diagnosed by: macimorelin stimulation test (cut point 5.1 mcg/L), or glucagon stimulation test (cut point: 3 mcg/L for BMI up to 25; cut point 1 mcg/L for BMI 25 and above) and IGF-I lab values have to be less than or equal to +1 SDS at baseline 6. Score of 11 or more on QoL-AGHDA 7. 4-week stability on any psychotropic medications 8. 3-month stability on all other hormone treatments 9. Able and willing to provide informed consent to participate in this study, and complete study protocol.
Exclusion criteria
1. History of moderate or severe TBI 2. History of neurologic disorder other than TBI with substantial impact on quality of life 3. History of bipolar disorder, schizophrenia, or other concurrent psychotic disorder 4. 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. 5. Contraindication to rhGH therapy 6. Acute medical illness, active infection, cancer or decompensated chronic medical illness 7. 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. 8. Score less than or equal to 41 on Trial 2 or Retention Trial of the Test of Memory and Malingering (TOMM). 9. BMI \> 40 or body weight \> 350 lbs 10. 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) 11. Women who are pregnant or of child-bearing potential not on contraception 12. Current use of the following: growth hormone, estrogen or estrogen-like dietary supplements, progestin, IGF-I, or chronic glucocorticoid use in supraphysiologic doses 13. Currently enrolled in any other interventional study unless prior approval is provided by the study chairs and the study sponsor (Cooperative Studies Program)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| QoL-AGHDA (Quality of Life-Assessment of Adult Growth Hormone in Adults) | 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 the investigators, 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
| Measure | Time frame | Description |
|---|---|---|
| Body Composition | 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. |
Countries
United States
Contacts
CONTACTDeane V Walker, MHA BS AB
CONTACTMichael T Wininger, PhD
STUDY_CHAIRJose M. Garcia, MD PhD
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Outcome results
None listed