Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06294860 |
| Other study ID # |
01C317 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 19, 2023 |
| Est. completion date |
December 31, 2024 |
Study information
| Verified date |
March 2024 |
| Source |
Istituto Auxologico Italiano |
| Contact |
Alessandro Sartorio, MD |
| Phone |
+390261911 |
| Email |
sartorio[@]auxologico.it |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The primary objective of the study is to evaluate the epigenetic age in children with GH
deficiency, before and after 6 months of treatment with growth hormone replacement therapy.
The secondary objective is to correlate the epigenetic age with the auxometric and
biochemical parameters used in the clinical-endocrinological practice. The results of the
study will be useful to set up the clinical and biochemical follow-up of the hormone
replacement therapy with rhGH and to understand the biomolecular mechanisms at the base of
the debated "anti" or "pro" aging action of GH, the most important anabolic hormone of the
human organism.
Description:
12 children of both sexes affected by an isolated GH deficiency (defined according to the
criteria provided by the note 39 AIFA for this pathology: short stature: ≤ -3 DS or ≤ -2 DS;
growth rate/year ≤ -1.0 DS per age and sex evaluated at a distance of at least six months; GH
peak at two different pharmacological stimulation tests < 8 ng/ml), recruited at the Regional
Reference Centre for Growth Disorders, Istituto Auxologico Italiano, IRCCS, Milano. The
exclusion criteria for the study (and from the rhGH treatment) are the presence of organic
hypothalamic-pituitary pathologies (diagnosed through encephalic RMN).
In basal conditions (pre-treatment), the clinical and anthropometric/auxometric data (height,
weight, BMI) are collected, including the evaluation of the body composition with
bioelectrical impedance analysis. The same evaluations is repeated after 6 months of
treatment with recombinant growth hormone (see below).
Each subject is treated with replacement therapy with rhGH at a dose of 0.025-0.035 mg/kg
body weight per day (or 0.7-1.0 mg/ m2 body surface area per day).
Blood samples for the determination of: glycemia, insulin, HbA1C, triglycerides, total
cholesterol, LDL, HDL, hsPCR, IGF-1, osteocalcin, ICTP, and PIIINP are collected at T0
(before the start of the hormone replacement therapy with rhGH) and at T6 (after 6 months of
rhGH, approximately 10-12 from the last dosing).
From the leucocytes isolated from the samples taken at T0 and T6, the DNA is extracted. The
DNA methylation is performed with sodium bisulfite and PCR- Pyrosequencing.
The biological age (epigenetic) is measured with two algorithms of Zbiec-Piekarska and of
Daunay, based on DNA methylation level in specific loci. To have an estimate of the
epigenetic age (biological) that is independent of the chronological age, a defined measure
defined as age acceleration will be used, for which calculation a linear regression model
will be applied with the chronological age as independent variable and the epigenetic age as
dependent variable; the difference between the observed value and the predicted value from
the model represents the age acceleration due to a properly epigenetic effect. In case the
epigenetic age is higher than the chronological age, the age acceleration has a positive
value expressed in years, otherwise negative.
