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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Growth Hormone Replacement Therapy | Active Comparator | Recombinant Human Growth Hormone |
|
| Placebo | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Somatropin | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 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). | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Depressive and Anxiety Symptoms measured by Depression Anxiety and Stress Scale (DASS-21) | Tertiary endpoint of interest: Depressive and anxiety symptoms measured by DASS-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. | 6 months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Deane V Walker, MHA BS AB | Contact | (203) 937-3440 | 3787 | Deane.Walker@va.gov |
| Michael T Wininger, PhD | Contact | (203) 932-5711 | 3262 | michael.wininger@va.gov |
| Name | Affiliation | Role |
|---|---|---|
| Jose M. Garcia, MD PhD | VA Puget Sound Health Care System Seattle Division, Seattle, WA | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Birmingham VA Medical Center, Birmingham, AL | Not yet recruiting | Birmingham | Alabama | 35233-1927 | United States |
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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Two arm study: active drug vs placebo
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|
| Placebo | Other | 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. |
|
| 6 months |
| Cognition | Tertiary endpoint of interest: Cognitive functioning will be assessed the Color Word Interference Test for cognitive flexibility and inhibition; the Digit Span test for working memory capacity; the Trail Making Test for processing speed, cognitive flexibility, and attention; the Grooved Pegboard for fine motor control and coordination; the Letter Fluency Test for verbal fluency and executive function; and the Rey Auditory Verbal Learning Test for verbal learning, memory, and attention. All test scores will be converted to z-scores, which standardize the results based on the mean and standard deviation of the normative sample, then averaged to generate a composite score, with higher scores indicating better performance relative to the normative sample. Both, individual test scores and the composite score will be analyzed to evaluate whether six-month recombinant human Growth Hormone treatment has any significant effect on cognitive performance. | 6 months |
| Severity of Fatigue Symptoms | 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. | 6 months |
| Sleep Quality | 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. | 6 months |
| Chronic Pain Assessment | 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. | 6 months |
| Phoenix VA Health Care System, Phoenix, AZ | Not yet recruiting | Phoenix | Arizona | 85012 | United States |
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| VA San Diego Healthcare System, San Diego, CA | Not yet recruiting | San Diego | California | 92161-0002 | United States |
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| Rocky Mountain Regional VA Medical Center, Aurora, CO | Not yet recruiting | Aurora | Colorado | 80045-7211 | United States |
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| Washington DC VA Medical Center, Washington, DC | Not yet recruiting | Washington D.C. | District of Columbia | 20422-0001 | United States |
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| Atlanta VA Medical and Rehab Center, Decatur, GA | Active, not recruiting | Decatur | Georgia | 30033-4004 | United States |
| VA Ann Arbor Healthcare System, Ann Arbor, MI | Not yet recruiting | Ann Arbor | Michigan | 48105-2303 | United States |
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| Minneapolis VA Health Care System, Minneapolis, MN | Recruiting | Minneapolis | Minnesota | 55417-2309 | United States |
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| Kansas City VA Medical Center, Kansas City, MO | Not yet recruiting | Kansas City | Missouri | 64128-2226 | United States |
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| Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE | Not yet recruiting | Omaha | Nebraska | 68105-1850 | United States |
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| Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC | Not yet recruiting | Salisbury | North Carolina | 28144 | United States |
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| Oklahoma City VA Medical Center, Oklahoma City, OK | Not yet recruiting | Oklahoma City | Oklahoma | 73104-5007 | United States |
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| VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX | Not yet recruiting | Dallas | Texas | 75216-7167 | United States |
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| Michael E. DeBakey VA Medical Center, Houston, TX | Recruiting | Houston | Texas | 77030-4211 | United States |
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| South Texas Health Care System, San Antonio, TX | Not yet recruiting | San Antonio | Texas | 78229-4404 | United States |
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| VA Puget Sound Health Care System Seattle Division, Seattle, WA | Recruiting | Seattle | Washington | 98108-1532 | United States |
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| ID | Term |
|---|---|
| D004393 | Dwarfism, Pituitary |
| D001924 | Brain Concussion |
| ID | Term |
|---|---|
| D004392 | Dwarfism |
| D001848 | Bone Diseases, Developmental |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D001849 | Bone Diseases, Endocrine |
| D007018 | Hypopituitarism |
| D010900 | Pituitary Diseases |
| D007027 | Hypothalamic Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D004700 | Endocrine System Diseases |
| D000070642 | Brain Injuries, Traumatic |
| D001930 | Brain Injuries |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D016489 | Head Injuries, Closed |
| D014947 | Wounds and Injuries |
| D014949 | Wounds, Nonpenetrating |
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| ID | Term |
|---|---|
| D019382 | Human Growth Hormone |
| ID | Term |
|---|---|
| D013006 | Growth Hormone |
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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