Hormone Treatment in Growth Hormone and Testosterone Deficient Patients

Study Overview
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Brief Summary
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Growth hormone and gonadotropin deficiency after brain injury (traumatic brain injury, ischemic stroke, subarachnoidal hemorrhage): the effects of hormone replacement on cognition, quality of life and body composition Randomized, controlled, 3 arm (group 2: double-blind; groups 1 and 3: open), multi-center, pilot study (Phase II)

Detailed Description
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The aim of the study is to investigate the influence of growth-hormone replacement on cognition, quality of life, body mass index, body composition and reorganization of brain activity of hypopituitary patients in a stable, chronic phase after brain injury compared to control patients and the influence of testosterone replacement in gonadotropin deficient patients compared to placebo treated control patients.

Official Title
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Growth Hormone and Gonadotropin Deficiency After Brain Injury (Traumatic Brain Injury, Subarachnoidal Hemorrhage, Ischemic Stroke): the Effects of Hormone Replacement on Cognition, Quality of Life and Body Composition

Conditions
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Hormone Deficiency

Intervention / Treatment
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* Drug: Genotropin
* Drug: Testosterone undecannoate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Group 1: Age F/M Stable phase after TBI, SAH or IS Stable substitution of other hormonal axes GH below 6 ng/ml after stimulation with ITT or GH below cut-off in GHRH/arginine test using BMI-adjusted cut-off limits, GHRH/arginine test should be done only in patients denying or with a contraindication for ITT Written informed consent Group 2: Age M PSA in normal range Stable phase after TBI, SAH or IS Stable substitution of other hormonal axes Below 3.5 ng/ml testosterone Written informed consent Group 3: Age F/M Stable phase after TBI, SAH or IS GH higher 6 ng/ml after stimulation with ITT or GH below cut-off in GHRH/arginine test using BMI-adjusted cut-off limits, GHRH/arginine test should be done only in patients denying or with a contraindication for ITT Written informed consent Exclusion Criteria: Group 1: Pregnancy/lactation period Women of childbearing potential not using an adequate method of birth control Men not willing to use an adequate method of birth control Previous or concomitant medication with GH Hypersensitivity to GH Drug or alcohol abuse Condition which in opinion of investigator makes patient unsuitable for inclusion Participation in another clinical trial with investigational new drug Planned treatment or changes in established treatment with other drug which might significantly influence GH axis or cognitive function Non-ability to perform testing Presence of other conditions listed in contraindications or warnings in local SPC of GH Onset of GH-deficiency before BI Group 2: Men not willing to use an adequate method of birth control Previous or concomitant medication with androgens or anabolic steroids within 12 months Hypersensitivity to active substances or excipients of Nebido® Drug or alcohol abuse Condition which in opinion of investigator makes patient unsuitable for inclusion Participation in another clinical trial with investigational new drug Planned treatment or changes in established treatment with other drug which might influence gonadotrophic axis or cognitive function Severe disturbances in articulation, visual faculty, hearing Presence of other conditions listed in contraindications or warnings in local SPC of Nebido® Onset of hormonal deficiency before BI Suspicion or known history of prostate or breast cancer or other hormone dependent neo plasia as well as history of malignancy within last 5 years Abnormal finding on DRE PSA higher 4 ng/ml History of clinically significant post void residual urine before BI Suspicion or known history of liver tumor Blood coagulation irregularities presenting an increased risk of bleeding after i.m injections Hypercalcemia accompanying malignant tumors Sleep apnea Polycythemia Haematocrit higher than 50 % Concurrent use of DHEA, anabolic steroids, clomipramine, antiandrogens, estrogen, ACTH, corticosteroids, oxyphenbutazone Uncontrolled thyroid disorders like diabetes mellitus, epilepsia, migraine, hypertension, coronary heart disease as well as hepatic, renal or cardiac insufficiency Patients requiring or undergoing fertility treatment Condition which in opinion of investigator makes patient unsuitable for inclusion Non-ability to perform cognitive testing Onset of androgen deficiency before BI. Group 3: Previous or concomitant medication with androgens, GH or anabolic steroids within 12 months Drug or alcohol abuse Condition which in opinion of investigator makes patient unsuitable for inclusion Participation in another clinical trial with investigational new drug Planned treatment or changes in established treatment with other drug which might influence gonadotrophic axis or cognitive function Severe disturbances in articulation, visual faculty, hearing Non-ability to perform cognitive testing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Active Comparator: Genotropin<br>6 months Genotropin (open treatment) Daily dose: Male < 45 years: 0,4 mg; ≥ 45 years: 0,2 mg Female < 45 years: 0,5 mg; ≥ 45 years: 0,3 mg Starting with half of the dose for the first 4 weeks. | Drug: Genotropin<br>* Genotropin administered sc once a day by patient or caregiver.<br>* Other names: GH;|
| Active Comparator: Testosterone undecannoate<br>18 weeks testosterone undecanoate/placebo (double-blind treatment) 1000 mg/4 ml at baseline and after 6 weeks | Drug: Testosterone undecannoate<br>* Testosterone undecannoate administered twice (6 week Interval) im by investigator.<br>* Other names: Testo;|
| No Intervention: control group<br>No Intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life | Quality of Life (QoL) was measured with the following questionnaires prior to treatment and after treatment: SF-12 short-form health questionnaire (12 items, score: min. 12/max. 47) QoL-AGHDA Assessment of GHD in Adults (25 items: yes/no answers) EQ-5 D Euroquol (5 items, scale per items from 1 (no problems) to 3 (severe problems); 1 Likert scale (0 worst-100 best) to measure health status) BDI Beck Depression Inventory (21 items, score: min. 0/max. 63) PSQI Pittsburgh Sleep Quality Index: (4 items regarding sleep duration, 11 items regarding sleep quality, 1 item regarding sleeping medication, 2 item regarding daytime dysfunction, 1 item regarding sleeping habit; 5 items for third-party assessment) QOLIBRI Quality of Life after Brain Injury (37 items, scale per item from 1 (not at all) to 5 (very much) QoL was measured with difference between mean scores of the respective questionnaires, determined before and after treatment. | 6 months |