Phase 2 Randomized, Placebo-Controlled Clinical Trial of Recombinant Human Growth Hormone (rhGH) During Rehabilitation From Traumatic Brain Injury
Traumatic brain injury (TBI) is a major cause of death and disability, but there are currently no therapies with proven efficacy for optimizing regeneration of repair during rehabilitation. Using standard stimulation tests, as many as 40–50% of survivors of severe TBI have deficiency of one or more...
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| Format: | Article |
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2018.00520/full |
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| author | Rosemary Dubiel Librada Callender Cynthia Dunklin Caryn Harper Monica Bennett Lisa Kreber Richard Auchus Ramon Diaz-Arrastia |
| author_facet | Rosemary Dubiel Librada Callender Cynthia Dunklin Caryn Harper Monica Bennett Lisa Kreber Richard Auchus Ramon Diaz-Arrastia |
| author_sort | Rosemary Dubiel |
| collection | DOAJ |
| description | Traumatic brain injury (TBI) is a major cause of death and disability, but there are currently no therapies with proven efficacy for optimizing regeneration of repair during rehabilitation. Using standard stimulation tests, as many as 40–50% of survivors of severe TBI have deficiency of one or more pituitary hormones. Of these, the somatotropic axis is the most commonly affected, with Growth Hormone (GH) deficiency affecting ~20% of persons with severe TBI. Treatment with recombinant human Growth Hormone (rhGH) is generally effective in reversing the effects of acquired GH deficiency, but there is no evidence documenting functional or neurocognitive improvement after GH replacement in TBI patients. As a consequence, screening for GH deficiency and GH replacement when deficiency is found is not routinely performed as part of the rehabilitation of TBI survivors. Given that most of the recovery after TBI occurs within the first 6–12 months after injury and IGF-1 and GH are part of a coordinated restorative neurotrophic system, we hypothesized that patients will optimally benefit from GH therapy during the window of maximal neuroregenerative activity. We performed a Phase IIa, randomized, double-blind, placebo-controlled feasibility trial of recombinant human Growth Hormone (rhGH), starting at discharge from an inpatient rehabilitation unit, with follow up at 6 and 12 months. Our primary hypothesis was that treatment with rhGH in the subacute period would result in improved functional outcomes 6 months after injury. Our secondary hypothesis proposed that treatment with rhGH would increase IGF-1 levels and be well tolerated. Sixty-three subjects were randomized, and 40 completed the trial. At baseline, there was no correlation between IGF-1 levels and peak GH levels after L-arginine stimulation. IGF-1 levels increased after rhGH treatment, but it took longer than 1 month for levels to be higher than for placebo-treated patients. rhGH therapy was well-tolerated. The rhGH group was no different from placebo in the Disability Rating Scale, Glasgow Outcome Scale-Extended, or neuropsychological function. However, a trend toward greater improvement from baseline in Functional Independence Measure (FIM) was noted in the rhGH treated group. Future studies should include longer treatment periods, faster titration of rhGH, and larger sample sizes. |
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| language | English |
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| spelling | doaj.art-1d2f46b603a24d86bf991a1673e653a32022-12-21T18:40:16ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-09-01910.3389/fendo.2018.00520333781Phase 2 Randomized, Placebo-Controlled Clinical Trial of Recombinant Human Growth Hormone (rhGH) During Rehabilitation From Traumatic Brain InjuryRosemary Dubiel0Librada Callender1Cynthia Dunklin2Caryn Harper3Monica Bennett4Lisa Kreber5Richard Auchus6Ramon Diaz-Arrastia7Department of Physical Medicine and Rehabilitation, Baylor Institute for Rehabilitation, Dallas, TX, United StatesDepartment of Physical Medicine and Rehabilitation, Baylor Institute for Rehabilitation, Dallas, TX, United StatesDepartment of Physical Medicine and Rehabilitation, Baylor Institute for Rehabilitation, Dallas, TX, United StatesDepartment of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, United StatesDepartment of Physical Medicine and Rehabilitation, Baylor Institute for Rehabilitation, Dallas, TX, United StatesCenter for Neuro Skills, Bakersfield, CA, United StatesDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, United StatesDepartment of Neurology, University of Pennsylvania, Philadelphia, PA, United StatesTraumatic brain injury (TBI) is a major cause of death and disability, but there are currently no therapies with proven efficacy for optimizing regeneration of repair during rehabilitation. Using standard stimulation tests, as many as 40–50% of survivors of severe TBI have deficiency of one or more pituitary hormones. Of these, the somatotropic axis is the most commonly affected, with Growth Hormone (GH) deficiency affecting ~20% of persons with severe TBI. Treatment with recombinant human Growth Hormone (rhGH) is generally effective in reversing the effects of acquired GH deficiency, but there is no evidence documenting functional or neurocognitive improvement after GH replacement in TBI patients. As a consequence, screening for GH deficiency and GH replacement when deficiency is found is not routinely performed as part of the rehabilitation of TBI survivors. Given that most of the recovery after TBI occurs within the first 6–12 months after injury and IGF-1 and GH are part of a coordinated restorative neurotrophic system, we hypothesized that patients will optimally benefit from GH therapy during the window of maximal neuroregenerative activity. We performed a Phase IIa, randomized, double-blind, placebo-controlled feasibility trial of recombinant human Growth Hormone (rhGH), starting at discharge from an inpatient rehabilitation unit, with follow up at 6 and 12 months. Our primary hypothesis was that treatment with rhGH in the subacute period would result in improved functional outcomes 6 months after injury. Our secondary hypothesis proposed that treatment with rhGH would increase IGF-1 levels and be well tolerated. Sixty-three subjects were randomized, and 40 completed the trial. At baseline, there was no correlation between IGF-1 levels and peak GH levels after L-arginine stimulation. IGF-1 levels increased after rhGH treatment, but it took longer than 1 month for levels to be higher than for placebo-treated patients. rhGH therapy was well-tolerated. The rhGH group was no different from placebo in the Disability Rating Scale, Glasgow Outcome Scale-Extended, or neuropsychological function. However, a trend toward greater improvement from baseline in Functional Independence Measure (FIM) was noted in the rhGH treated group. Future studies should include longer treatment periods, faster titration of rhGH, and larger sample sizes.https://www.frontiersin.org/article/10.3389/fendo.2018.00520/fullinsulin-like growth factor Iglasgow outcome scaledisability rating scalefunctional independence measureshort form 36 |
| spellingShingle | Rosemary Dubiel Librada Callender Cynthia Dunklin Caryn Harper Monica Bennett Lisa Kreber Richard Auchus Ramon Diaz-Arrastia Phase 2 Randomized, Placebo-Controlled Clinical Trial of Recombinant Human Growth Hormone (rhGH) During Rehabilitation From Traumatic Brain Injury Frontiers in Endocrinology insulin-like growth factor I glasgow outcome scale disability rating scale functional independence measure short form 36 |
| title | Phase 2 Randomized, Placebo-Controlled Clinical Trial of Recombinant Human Growth Hormone (rhGH) During Rehabilitation From Traumatic Brain Injury |
| title_full | Phase 2 Randomized, Placebo-Controlled Clinical Trial of Recombinant Human Growth Hormone (rhGH) During Rehabilitation From Traumatic Brain Injury |
| title_fullStr | Phase 2 Randomized, Placebo-Controlled Clinical Trial of Recombinant Human Growth Hormone (rhGH) During Rehabilitation From Traumatic Brain Injury |
| title_full_unstemmed | Phase 2 Randomized, Placebo-Controlled Clinical Trial of Recombinant Human Growth Hormone (rhGH) During Rehabilitation From Traumatic Brain Injury |
| title_short | Phase 2 Randomized, Placebo-Controlled Clinical Trial of Recombinant Human Growth Hormone (rhGH) During Rehabilitation From Traumatic Brain Injury |
| title_sort | phase 2 randomized placebo controlled clinical trial of recombinant human growth hormone rhgh during rehabilitation from traumatic brain injury |
| topic | insulin-like growth factor I glasgow outcome scale disability rating scale functional independence measure short form 36 |
| url | https://www.frontiersin.org/article/10.3389/fendo.2018.00520/full |
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