Clinical trial NCT04352712: Gene Expression in Monocytes of Growth Hormone Deficient Children
Official title: Growth Hormone Modulated Gene Expression in Monocytes of Healthy and Growth Hormone Deficient Children
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Growth Hormone Deficiency
Lead sponsor: University of Salerno
Sponsor class: OTHER
First posted: 2020-04-20
Enrollment: 40
Sex: MALE
Minimum age (years): 6
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: primary care clinic

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.


Eligibility criteria: 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

Primary outcomes:
measure: gene expression in monocytes of GHD children
timeFrame: one year
Secondary outcomes:
measure: gene expression in monocytes modulated by GH
timeFrame: one year
Other outcomes:
Locations:
city: Baronissi
country: Italy
facility: Department of Medicine and Surgery, Univeristy of Salerno
state: Salerno
Study officials:
affiliation: University of Salerno
name: Mario Vitale, MD
role: STUDY_DIRECTOR
References: