Gene Expression in Monocytes of Growth Hormone Deficient Children

Brief Title

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

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.
    

Study Type

Observational

Primary Outcome

gene expression in monocytes of GHD children

Secondary Outcome

 gene expression in monocytes modulated by GH

Condition

Growth Hormone Deficiency

Intervention

blood sampling

Study Arms / Comparison Groups

 Healthy Children

Description:  healthy children, untreated, donors of monocytes

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Other

Estimated Enrollment

40

Start Date

April 15, 2019

Completion Date

April 15, 2021

Primary Completion Date

April 15, 2021

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
      

Gender

Male

Ages

6 Years - 10 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Mario Vitale, MD, 393482652847, [email protected]

Location Countries

Italy

Location Countries

Italy

NCT ID

NCT04352712

Organization ID

GHUSalerno

Responsible Party

Principal Investigator

Study Sponsor

University of Salerno

Study Sponsor

Mario Vitale, MD, Study Director, University of Salerno

Verification Date

April 2020