Clinical trial NCT06294860: Biological Age in Children With GH Deficiency Undergoing Hormone Replacement Therapy
Official title: Evaluation of Biological Age in Children With GH Deficiency Undergoing Hormone
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Growth Hormone Deficiency
Short Stature
Keywords: Growth hormone deficiency
Replacement therapy
Recombinant growth hormone
Short stature
Biological age
Epigenetic
Lead sponsor: Istituto Auxologico Italiano
Sponsor class: OTHER
First posted: 2024-03-06
Enrollment: 12
Sex: ALL
Minimum age (years): 5
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Children with isolated growth hormone deficiency

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

* children of both sexes
* age 5-15 years affected by isolated GH deficiency according to the criteria provided by 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).

Exclusion Criteria:

- presence of organic hypothalamic-pituitary pathologies (diagnosed through encephalic NMR).

Primary outcomes:
measure: Measurement of biological (epigenetic) age
timeFrame: Baseline and after 6 months of substitutive treatment with recombinant growth hormone
Secondary outcomes:
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Istituto Auxologico Italiano
Study officials:
affiliation: Istituto Auxologico Italiano
name: Alessandro Sartorio, MD
role: PRINCIPAL_INVESTIGATOR
References: