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Gene Expression in Monocytes of Growth Hormone Deficient Children

Conditions
Growth Hormone Deficiency
Interventions
Other: blood sampling
Registration Number
NCT04352712
Lead Sponsor
University of Salerno
Brief Summary

The Growth hormone (GH) is mainly synthesized in the anterior portion of the pituitary gland and has an effect on different body areas. Secreted in the circulatory stream, growth hormone reaches the liver and here stimulates the secretion of somatomedin C better known as insulin-like growth factor 1 (IGF), which constitutes its main anabolic effector.

Growth hormone deficiency (GHD) is characterized by a delay in the statural growth in children and is correlated with a worsening of body composition, cognitive functions, lipid metabolism, bone mineralization, cardiac performance and exercise in adults. Recombinant GH (rhGH) replacement therapy can correct these alterations and therefore improve the quality of life in treated patients, and accelerate growth in children.

The optimal dosage of rhGH varies for each patient, as the response to treatment suffers from considerable inter-individual variability. To date, IGF1 is the only available biomarker whose plasma levels correlate with replacement therapy.

It is important to underline how somatomedin C does not provide information about the optimal posology of rhGH for each patient in order, therefore, to predict its adverse events and efficacy.

In addition, it has been shown that the effects mediated by the somatotropic hormone on some tissues are direct, therefore independent of the action of IGF1, whose plasma levels are not, in this case, predictive of therapeutic response.

For this reason, it is therefore necessary to identify a more specific biomarker capable of monitoring the efficacy, individual responsiveness and any adverse events in patients receiving somatotropic hormone.

The GH receptor (GHR) is expressed in several cells, including monocytes. It is therefore possible that the response of monocytes to the somatotropic hormone partially mirrors that of the chondrocyte and other cell types. Given the difficulty of obtaining osteomuscular biopsies or specific body areas in which GH mediates its biological action, the published works have identified the specific cell line in which to study the molecular effects of the hormone in monocytes, thanks to their easy accessibility and high number of GHR.

In consideration of this, the investigators propose to stimulate monocytes of healthy and GHD children in vitro with rhGH and through next generation sequencing to identify the characteristic gene expression profile. The GH responsive genes identified with this study can be used for correlation studies on the response to rhGH treatment.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
Male
Target Recruitment
40
Inclusion Criteria
  • Height lower the 3th percentile
Exclusion Criteria
  • Any endocrinopathy
  • Liver, kidney or haemolymphopoietic system disorders
  • Celiac disease or other chronic malabsorption conditions
  • Genetic syndromes (such as Turner's S., Cystic fibrosis or Down S.)
  • Drug therapies interfering with growth

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
GHD childrenblood samplingGHD children, untreated, donors of monocytes
Healthy Childrenblood samplinghealthy children, untreated, donors of monocytes
Primary Outcome Measures
NameTimeMethod
gene expression in monocytes of GHD childrenone year

analysis of RNA-seq of monocytes of healthy and GHD children

Secondary Outcome Measures
NameTimeMethod
gene expression in monocytes modulated by GHone year

analysis of RNA-seq of monocytes of healthy and GHD children, stimulated with GH in culture

Trial Locations

Locations (1)

Department of Medicine and Surgery, Univeristy of Salerno

🇮🇹

Baronissi, Salerno, Italy

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