Clinical trial NCT01397500: Hormone Treatment in Growth Hormone and Testosterone Deficient Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hormone Deficiency
Lead sponsor: Max-Planck-Institute of Psychiatry
Sponsor class: OTHER
Collaborators: name: Schoen Clinic Bad Aibling
First posted: 2011-07-19
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

Group 1:

1. Age
2. F/M
3. Stable phase after TBI, SAH or IS
4. Stable substitution of other hormonal axes
5. 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
6. Written informed consent

Group 2:

1. Age
2. M
3. PSA in normal range
4. Stable phase after TBI, SAH or IS
5. Stable substitution of other hormonal axes
6. Below 3.5 ng/ml testosterone
7. Written informed consent

Group 3:

1. Age
2. F/M
3. Stable phase after TBI, SAH or IS
4. 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
5. Written informed consent

Exclusion Criteria:

Group 1:

1. Pregnancy/lactation period
2. Women of childbearing potential not using an adequate method of birth control
3. Men not willing to use an adequate method of birth control
4. Previous or concomitant medication with GH
5. Hypersensitivity to GH
6. Drug or alcohol abuse
7. Condition which in opinion of investigator makes patient unsuitable for inclusion
8. Participation in another clinical trial with investigational new drug
9. Planned treatment or changes in established treatment with other drug which might significantly influence GH axis or cognitive function
10. Non-ability to perform testing
11. Presence of other conditions listed in contraindications or warnings in local SPC of GH
12. Onset of GH-deficiency before BI

Group 2:

1. Men not willing to use an adequate method of birth control
2. Previous or concomitant medication with androgens or anabolic steroids within 12 months
3. Hypersensitivity to active substances or excipients of Nebido®
4. Drug or alcohol abuse
5. Condition which in opinion of investigator makes patient unsuitable for inclusion
6. Participation in another clinical trial with investigational new drug
7. Planned treatment or changes in established treatment with other drug which might influence gonadotrophic axis or cognitive function
8. Severe disturbances in articulation, visual faculty, hearing
9. Presence of other conditions listed in contraindications or warnings in local SPC of Nebido®
10. Onset of hormonal deficiency before BI
11. 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
12. Abnormal finding on DRE
13. PSA higher 4 ng/ml
14. History of clinically significant post void residual urine before BI
15. Suspicion or known history of liver tumor
16. Blood coagulation irregularities presenting an increased risk of bleeding after i.m injections
17. Hypercalcemia accompanying malignant tumors
18. Sleep apnea
19. Polycythemia
20. Haematocrit higher than 50 %
21. Concurrent use of DHEA, anabolic steroids, clomipramine, antiandrogens, estrogen, ACTH, corticosteroids, oxyphenbutazone
22. Uncontrolled thyroid disorders like diabetes mellitus, epilepsia, migraine, hypertension, coronary heart disease as well as hepatic, renal or cardiac insufficiency
23. Patients requiring or undergoing fertility treatment
24. Condition which in opinion of investigator makes patient unsuitable for inclusion
25. Non-ability to perform cognitive testing
26. Onset of androgen deficiency before BI.

Group 3:

1. Previous or concomitant medication with androgens, GH or anabolic steroids within 12 months
2. Drug or alcohol abuse
3. Condition which in opinion of investigator makes patient unsuitable for inclusion
4. Participation in another clinical trial with investigational new drug
5. Planned treatment or changes in established treatment with other drug which might influence gonadotrophic axis or cognitive function
6. Severe disturbances in articulation, visual faculty, hearing
7. Non-ability to perform cognitive testing

Primary outcomes:
measure: Quality of Life
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Muenchen
country: Germany
facility: Max Planck Institute
state: Bavaria
Study officials:
affiliation: Max Planck Institute
name: Caroline Sievers, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leonhardt M, Kopczak A, Schapers B, Limbrock J, Samann PG, Czisch M, von Steinbuechel N, Jordan M, Schneider HJ, Schneider M, Sievers C, Stalla GK. Low Prevalence of Isolated Growth Hormone Deficiency in Patients After Brain Injury: Results From a Phase II Pilot Study. Front Endocrinol (Lausanne). 2018 Dec 17;9:723. doi: 10.3389/fendo.2018.00723. eCollection 2018.