Treatment Of Adult Growth Hormone Deficiency After Traumatic Brain Injury

Study Overview
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Brief Summary
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To establish the effects of genotropin replacement on cognitive function in patients with severe growth hormone deficiency after traumatic brain injury.

Detailed Description
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The study was terminated on 15-Dec-2008 due to an inability to recruit the protocol specified patient population. The study has not been terminated due to any safety concerns.

Official Title
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Placebo Controlled Trial on the Efficacy of Growth Hormone Replacement Therapy in Patients With Growth Hormone Deficiency After Traumatic Brain Injury.

Conditions
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Brain Injuries, Growth Hormone Deficiency

Intervention / Treatment
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* Drug: Genotropin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have had a previous traumatic brain injury (more than 1 year and less than 20 years) prior to the screening visit. Have an Extended Glasgow Outcome Scale (GOS-E) more than or equal to 5. Have proven GHD deficiency Exclusion Criteria: Active systemic malignancy or active intracranial tumor. A successfully treated tumor or malignancy is not an exclusion criterion if the patient has not had active disease for 5 years and is not currently receiving maintenance chemotherapy, (except for basal cell skin cancers. Receiving treatment with prednisolone in doses above 10 mg/day or treatment with other oral glucocorticosteroids above replacement doses is not permitted throughout the study. Topical and inhaled corticosteroids are permitted. History of dementia unrelated to TBI History of benign intracranial hypertension

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Genotropin treatment arm<br> | Drug: Genotropin<br>* Subcutaneous injection, starting dose 0.2mg/day for males and 0.3mg/day for female with dose titration at 0.1mg to 0.2 mg increments in accordance to IGF-1 results for a total duration of 36 weeks.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Subcutaneous injection, with dummy dose titration for a total duration of 36 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Cognitive Function (CogState™) Composite Score at Week 36 | CogState™: 7 tasks: Detection (Part A); Identification; One back working memory; Monitoring; One card learning; Prediction; Detection (Part B). Detection, Identification, Monitoring score range: 2 (worse) to 5 (best); One back working memory/one card learning score range: 0 (worse) to 1.57 (best); Prediction score range: 0 (worse) to 100 (best). Composite change score=average of cognitive change scores for each task at each postdrug assessment; total possible score: -300 to 300. Change=change from baseline (average of 2 postdose assessments). Positive composite score=improved performance. | Baseline, Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in CogState™ at Week 12 and 24. | CogState™: 7 tasks: Detection (Part A); Identification; One back working memory; Monitoring; One card learning; Prediction; Detection (Part B). Detection, Identification, Monitoring score range: 2 (worse) to 5 (best); One back working memory/one card learning score range: 0 (worse) to 1.57 (best); Prediction score range: 0 (worse) to 100 (best). Composite change score=average of cognitive change scores for each task at each postdrug assessment; total possible score: -300 to 300. Change=change from baseline (average of 2 postdose assessments). Positive composite score=improved performance. | Baseline, Week 12 and 24 | 
| Change From Baseline in Lean Body Mass and Fat Mass at Week 36 | The change from Baseline values for lean body mass and fat mass is calculated as the difference between the parameter values at Visit 36, and the parameter values at Baseline. | Baseline, Week 36 | 
| Change From Baseline in Neurological Outcome as Assessed by Extended Glasgow Outcome Scale (GOS-E) at Week 36 | The GOS is widely used for assessing outcome after head injury and non-traumatic acute brain insults and is performed by a physician. The GOS-E uses eight points to assess disability and handicap. The GOS-E focuses on how the injury has affected functioning in major areas of life rather than on the particular deficits and symptoms caused by injury. The overall score ranges from 1-8; 1=Death and 8=Upper Good Recovery | Baseline, Week 36 | 
| Change From Baseline in Quality of Life Using Short Form (SF)-36 Health Survey at Week 36 | A subject administered scale assessing general quality of life. A subject administered score, scale, direction of scale. The SF-36 consists of 36 questions covering the following eight health domains (subscales): Physical Functioning, Bodily Pain, Role Limitations Due to Physical Problems, Role Limitations Due to Emotional Problems, General Health Perceptions, Mental Health, Social Function, Vitality. | Baseline, Week 36 | 
| Change From Baseline In Assessment of Growth Hormone Deficiency in Adults (AGHDA) Questionnaires at Week 36 | The AGHDA is a quality of life subject-administered questionnaire that is condition-specific and comprises of 25 'Yes' or 'No' statements covering 6 dimensions - mobility, pain, energy, sleep, emotional reactions and social isolation. The AGHDA total score change from Baseline values is calculated as the difference between the total score at Visit 6 (Week 36), and the total score at Baseline. | Baseline, Week 36 | 
| Change From Baseline in Cardiovascular Risk | The cardiovascular risk parameters (low-density lipoprotein-cholesterol, high-density lipoprotein cholesterol, total cholesterol and fasting triglycerides) was measured at all visits (Weeks 2, 4, 12, 24, and 36). | Baseline, Weeks 2, 4, 12, 24, and 36 | 
| Change From Baseline in Weight |  | Baseline, Weeks 2, 4, 12, 24, and 36 | 
| Change From Baseline in Waist Circumference |  | Baseline, Weeks 2, 4, 12, 24, and 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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traumatic brain Injury, cognitive function