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GH deficiency in patients with spinal cord injury: efficacy/safety of GH replacement, a pilot study.

ABSTRACT: Objective Growth hormone (GH) was shown to stimulate proliferation, migration and survival of neural cells in animal models. GH deficiency (GHD) was reported following traumatic brain lesions; however, there are not available data in spinal cord injury (SCI) patients. The aim of the study was to evaluate (1) the frequency of GHD in chronic SCI population; (2) the efficacy/safety of GH replacement in patients with SCI and suboptimal GH secretion. Design and methods Nineteen consecutive patients with chronic thoracic complete SCI (AIS-A) were studied. Patients with low GH secretion were randomized in a double-blind, placebo-controlled study to receive either subcutaneous placebo injections or GH combined with physical therapy, for 6 months. Baseline cranial MRI, AIS motor and sensory scale, quality of life (spinal cord impact measurement) and modified Ashworth spasticity scale, quantitative sensory testing and neurophysiological exploration were assessed at baseline, 1, 3 and 6 months following treatment. Results Thirteen had GH deficiency. Seven received GH, five placebo and one dropped out. Both groups were similar according to clinical and demographical data at baseline, except for greater GH deficiency in the GH treatment group. At 6th month, patients treated with GH showed a significant improvement in SCIM-III score and in electrical perception threshold up to the 5th level below SCI, on both sides compared to baseline. Conclusions GHD seems to be frequent in traumatic SCI and GH replacement is safe without side effects. GH combined with physical therapy can improve quality of life of SCI patients and, strikingly, the sensory perception below lesion level.

SUBMITTER: Cuatrecasas G

PROVIDER: S-EPMC6198193 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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GH deficiency in patients with spinal cord injury: efficacy/safety of GH replacement, a pilot study.

Cuatrecasas Guillem G Kumru Hatice H Coves M Josep MJ Vidal Joan J

Endocrine connections 20181001 10

Objective Growth hormone (GH) was shown to stimulate proliferation, migration and survival of neural cells in animal models. GH deficiency (GHD) was reported following traumatic brain lesions; however, there are not available data in spinal cord injury (SCI) patients. The aim of the study was to evaluate (1) the frequency of GHD in chronic SCI population; (2) the efficacy/safety of GH replacement in patients with SCI and suboptimal GH secretion. Design and methods Nineteen consecutive patients w ...[more]

PMID: 30352393

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Project description:BackgroundDespite age-related adipose involution, T cell generation in the thymus (thymopoiesis) is maintained beyond puberty in adults. In rodents, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and GH secretagogues reverse age-related changes in thymus cytoarchitecture and increase thymopoiesis. GH administration also enhances thymic mass and function in HIV-infected patients. Until now, thymic function has not been investigated in adult GH deficiency (AGHD). The objective of this clinical study was to evaluate thymic function in AGHD, as well as the repercussion upon thymopoiesis of GH treatment for restoration of GH/IGF-1 physiological levels.Methodology/principal findingsTwenty-two patients with documented AGHD were enrolled in this study. The following parameters were measured: plasma IGF-1 concentrations, signal-joint T-cell receptor excision circle (sjTREC) frequency, and sj/beta TREC ratio. Analyses were performed at three time points: firstly on GH treatment at maintenance dose, secondly one month after GH withdrawal, and thirdly one month after GH resumption. After 1-month interruption of GH treatment, both plasma IGF-1 concentrations and sjTREC frequency were decreased (p<0.001). Decreases in IGF-1 and sjTREC levels were correlated (r = 0.61, p<0.01). There was also a decrease in intrathymic T cell proliferation as indicated by the reduced sj/beta TREC ratio (p<0.01). One month after reintroduction of GH treatment, IGF-1 concentration and sjTREC frequency regained a level equivalent to the one before GH withdrawal. The sj/beta TREC ratio also increased with GH resumption, but did not return to the level measured before GH withdrawal.ConclusionsIn patients with AGHD under GH treatment, GH withdrawal decreases thymic T cell output, as well as intrathymic T cell proliferation. These parameters of thymus function are completely or partially restored one month after GH resumption. These data indicate that the functional integrity of the somatotrope GH/IGF-1 axis is important for the maintenance of a normal thymus function in human adults.Trial registrationClinicalTrials.gov NTC00601419.

Project description:INTRODUCTION:Acute traumatic spinal cord injury (tSCI) is a devastating neurological disorder with no pharmacological neuroprotective strategy proven effective to date. Progressive haemorrhagic necrosis (PHN) represents an increasingly well-characterised mechanism of secondary injury after tSCI that negatively impacts neurological outcomes following acute tSCI. Preclinical studies evaluating the use of the Food and Drug Administration-approved sulfonylurea receptor 1-transient receptor potential melastatin 4 channel blocker glyburide in rodent models have shown reduced secondary microhaemorrhage formation and the absence of capillary fragmentation, the pathological hallmark of PHN. METHODS AND ANALYSIS:In this initial phase multicentre open-label pilot study, we propose to enrol 10 patients with acute cervical tSCI to primarily assess the feasibility, and safety of receiving oral glyburide within 8?hours of injury. Secondary objectives include pharmacokinetics and preliminary evaluations on neurological recovery as well as blood and MRI-based injury biomarkers. Analysis will be performed using the descriptive and non-parametric statistics. ETHICS AND DISSEMINATION:Glyburide has been shown as an effective neuroprotective agent in preclinical tSCI models and in the treatment of ischaemic stroke with the additional risk of a hypoglycaemic response. Given the ongoing secondary injury and the traumatic hyperglycaemic stress response seen in patients with tSCI, glyburide; thus, offers an appealing neuroprotective strategy to supplement standard of care treatment. The study protocol was approved by the Ohio State University Biomedical Institutional Review Board. The protocol was amended in February 2017 with changes related to study feasibility and patient recruitment. Specifically, the route of administration was changed to the oral form to allow for streamlined and rapid drug administration, and the injury-to-drug time window was extended to 8?hours in an effort to further enhance enrolment. Participants or legally authorised representatives are informed about the trial and its anticipated risks orally and in written form using an approved informed consent form prior to inclusion. The findings of this study will be disseminated to the participants and to academic peers through scientific conferences and peer-reviewed journal publications. TRIAL REGISTRATION NUMBERS:NCT02524379 and 2014H0335.

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GH deficiency in patients with spinal cord injury: efficacy/safety of GH replacement, a pilot study.

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GH deficiency in patients with spinal cord injury: efficacy/safety of GH replacement, a pilot study.

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