To evaluate whether GH substitution in patients with an isolated GHD after TBI could reverse the severity of symptoms which characterize GHD.
ID
Source
Brief title
Condition
- Other condition
- Hypothalamus and pituitary gland disorders
- Structural brain disorders
Synonym
Health condition
traumatologische aandoeningen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. change in different components of the GHD syndrome, before and after GH
substitution, in patients with TBI
2. change in physical and neuro-cognitive factors, not necessarily associated
with GHD syndrome, before and after GH substitution, in patients with TBI
Secondary outcome
not applicable
Background summary
Traumatic brain injury (TBI) is a frequent cause of morbidity and mortality in
young adults. Most of the patients have impaired physical and psychological
functioning. Most of these impairments cannot be explained by direct tissue
damage due to trauma.
It was found recently that individuals with a TBI display pituitary
insufficiency, ranging from isolated defects to multiple defects of pituitary
hormonal axes. Most often an isolated defect was found in the somatotropic
axes, an isolated growth hormone deficiency (in about 10% of all TBI patients).
The classical syndrome of growth hormone deficiency (GHD) in adulthood is
characterized by a change in body composition with an increase in
intraabdominal fat (and consequently an increased risk profile for
cardiovascular disease; eg. a proatherogenic lipid profile), impaired cognitive
function and a decrease in Quality of Life. Interestingly, this complex of
symptoms is highly similar to those which are observed among individuals after
TBI. Intervention with recombinant GH in adults is a safe and experienced mode
of treatment.
Study objective
To evaluate whether GH substitution in patients with an isolated GHD after TBI
could reverse the severity of symptoms which characterize GHD.
Study design
intervention study with an Off-On-Off treatment design
Intervention
Patients with an isolated GHD will be evaluated at baseline (Off treatment),
after 12 months recombinant GH (Norditropin Simplexx) substitution (On
treatment), and 6 months after stop of GH substitution (Off treatment). The
daily dosage of rGH will be titrated on plasma IGF-1 levels, adjusted for age
and sex. Patients will visit the out patiënt clinic of the department of
Endocrine Diseases during the period of rGH substitution.
Study burden and risks
GHD in adulthood is a well recognized clinical entity with an option for
adequate treatment. Substitution with rGH, especially with actual low dose
regimens, is not frequently associated with major side effects. Minor side
effects consist of mild oedema of the legs and joints which could manifest the
first months after start of rGH substitution. Therefore, identification of a
GHD state in patients with a history of TBI indeed offers additional
opportunities to improve their general condition. This study protocol only
consists of regular methods which are daily practice, eg. venous puncture and
completion of questionnaires (with collection of 45 ml of venous blood each
visit). In order to assess cardiac performance, a transthoracal ultrasound is
performed at visit 0, visit 12 months and a visit 18 months (in collaboration
with dr MJM Cramer, UMCU, the Netherlands)
Reinier postlaan 4
6500 HB Nijmegen
NL
Reinier postlaan 4
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
1. The patient visits the emergency department with mild, moderate or severe traumatic brain injury. (Mild traumatic brain injury is defined as a history of impact to the head and a Glasgow Coma Scale score (GCS) 13-15 at entry in the emergency room, moderate traumatic brain injury is defined as a GCS 9-12 at entry in the emergency room, and severe traumatic brain injury is defined as a GCS <= 8 at entry in the emergency room)
2. The trauma has occurred less than 24 hours before visiting the emergency department.
3. Age >= 18 years and <= 65 years at the time of inclusion
4. Absolute growth hormone deficiency (defined as growth hormone response < 9 mE/l in the GHRH-arginine test), diagnosed within one of the protocols going with ABR form no. 14996 or 14998
Exclusion criteria
1. Age > 65 or < 18 years
2. No oral or written informed consent by patient
3. Pre-existent neuro-endocrine disorder
4. Co-existent dysfunction of pituitary axis other than the somatotropic axis
5. Instable infiltrative disease in the hypothalamus/pituitary region (eg sarcoidosis, tumour metastasis)
6. BMI >30 kg/m2
7. Primary dyslipidemia that necessitates treatment
8. Positive family history of premature cardiovascular disease
9. Overt diabetes mellitus type II (including a history of gestational diabetes mellitus)
10. Impairment in renal function (Creatinin clearance < 60 ml/min)
11. Pregnancy or wish for pregnancy during the study period, lactation
12. Retinal disease
13. History of neoplasmata
14. Co-existent disease with decreased life expectancy, especially active malignant tumor
15. Chronic alcohol or drug abuse
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-005442-37-NL |
| CCMO | NL14034.091.06 |