To assess the impact of treatment with rhGH on circulating Klotho levels in paediatric patients with IGHD.
ID
Source
Brief title
Condition
- Hypothalamus and pituitary gland disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The absolute change in sKlotho levels in serum and urine before and after
treatment with rhGH in paediatric patients with IGHD.
Secondary outcome
not applicable.
Background summary
The GH - IGF-1 axis is a major controller of cell and tissue growth and
development in human. Stimulation of the pituitary gland under the influence of
hypothalamic hormones leads to pulsatile output of GH from the pituitary,
leading to increased activation of hepatic GH receptors and IGF-1 production.
IGF-1 is a key peptide involved in growth and cellular proliferation. GH and
IGF-1 also have major effects on kidney growth, structure and function and
their overall activities are reduced in patients with CKD.
Klotho is an anti-aging gene and overexpression leads to an extended life span.
Klotho deficiency however, as is the case with patients with CKD, is associated
with premature aging, progression of renal function loss, development of
arterial stiffness, vascular calcification, cardiac hypertrophy, and secondary
hyperparathyroidism. Restoring Klotho levels in different CKD mouse-models
resulted in an impressive amelioration of the kidney injury. Therefore,
upregulation of endogenous Klotho might provide novel treatment strategies not
only to preserve remnant kidney function but also to minimize complications of
CKD. Recent data show that patients with acromegaly, in which the production of
GH and IGF-1 by the anterior pituitary gland is excessive, also have
dramatically elevated levels of sKlotho. After transsphenoidal resection of the
GH-producing adenoma, these elevated sKlotho levels returned rapidly towards
normal. This strongly suggests that GH or IGF-1 are physiological inducers of
Klotho. We hypothesize that exogenously delivered GH may induce higher levels
of Klotho.
As far as we know, no research is ever done to assess sKlotho levels in
paediatric patients with IGHD. In this observational study we will determine
the levels of sKlotho and IGF-1 in serum samples from paediatric patients with
IGHD before and after treatment with GH.
Study objective
To assess the impact of treatment with rhGH on circulating Klotho levels in
paediatric patients with IGHD.
Study design
Open, prospective, multi-center, explorative study.
Study burden and risks
Not applicable.
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
- Subjects with newly diagnosed GHD according to the guideline *Guideline for GH treatment in children* with an indication for treatment with rhGH .
- Boys < 9 years old and girls < 8 years old (pre-pubertal).
- No history of rhGH treatment in the last 6 months.
- Providing informed consent by the parents.
Exclusion criteria
- Subjects with a combined pituitary hormone deficiency.
- Patients taking medications or having concomitant illnesses likely to confound endpoint assessments (e.g.use of corticosteroids, androgens or anabole steroids, insulin).
- Patients with hypothyroidism not adequately supplied with thyroid hormone.
- Patients taking other experimental (i.e., non marketed) therapies.
- Patients with any kind of kidney disease.
- Patients with a single kidney.
Design
Recruitment
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 |
|---|---|
| CCMO | NL48068.029.14 |