miRNA as a Growth Plate Marker After GH

NCT05946915 | Unknown

• 1 other identifier: 67005222.0.0000.5479
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The therapeutic use of recombinant human growth hormone usually determines adequate growth response in the majority of approved conditions. However, it is well recognized an inter-individual responsiveness, and the classical biomarker such as GH peak response, IGF-I or IGFBP3 levels have poor correlation with clinical outcome. We hypothesize that markers directed originated from the growth plate would have the potential to better correlate with growth response during GH treatment. Genetic markers, as the growth hormone receptor exon 3-deletion polymorphism, IGFBP3 polymorphisms were previously tested in an attempt to discriminate the pattern of responsiveness, but results were contradictory in the different studies. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Due to their ability to regulate gene expression, miRNAs play an important role both in physiology and pathophysiological conditions, and also an important role in the regulation of endochondral ossification and regulation of the hypothalamic-pituitary-IGF axis. Several miRNAs are already recognized as involved in the regulation of longitudinal growth and bone development, through its action upon WNT-βcatenin, Notch, PI3K/AKT and TGFβ signaling pathways. AIM: Therefore, the aim of this study is to establish a panel of miRNAs correlated to the growth response during GH treatment, that can be used of biomarker for early recognition and classification of patients according to GH therapy responsiveness. This study will analyze 30 Children and adolescents with GH deficiency associated with Ectopic Posterior Pituitary (EPP) gland. METHODS: Clinical, biochemical and miRNAs concentration will be measured at four time-points: before starting therapy (basal), and after 1-, 3- and 6-months during GH treatment. Studied variables include: height, target height, growth velocity and body mass index, bone age and pubertal stage. Laboratory Assessment: at basal condition: fasting glucose, insulin, TSH and free T4; and cortisol, and IGF-I at 3 and 6 months. Bone age at basal and 6 months of therapy. MiRNAs will be measured in peripheral blood sample obtained before starting GH therapy, after 1-, 3- and 6-months during GH treatment. A miRNA panel will be measured by absolute quantitative method (digital PCR). The identification of a panel of miRNAs that correlates with GH responsiveness offers a huge clinical applicability, allowing prompt identification of patients who need differential therapeutic protocols targeted to achieve the best response during GH treatment.

Conditions

MicroRNAs: D13.444.735.790.552.500

Outcome Measures

Primary Outcomes (2)

• Variation in microRNAs concentration

  serial serum microRNAs concentration

  basal to six-months

• Variation in height SDS

  serial height SDS measurement

  basal to six-months

Eligibility Criteria

• Age: Up to 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Thirty patients with pituitary insufficiency related to Ectopic Posterior Pituitary gland

You may qualify if:

• GH stimulation test showing GH-peak concentration \<5ng/ml, combined to magnetic resonance imaging showing Posterior Pituitary Ectopic gland (EPP). Patients with combined hormone deficiencies must be compensated during the study period.

You may not qualify if:

• chronic diseases, need of prolonged supraphysiologic doses of glucocorticoids, bone age \>14 years or \>16 years (girls and boys, respectively), patients missing adequate follow-up

Sponsors & Collaborators

• Faculdade de Ciências Médicas da Santa Casa de São Paulo: lead
• Pfizer: collaborator

Study Sites (1)

Santa Casa SP School of Medical Sciences

São Paulo, São Paulo, 01221-020, Brazil

RECRUITING

Related Publications (1)

• Pellicciari CR, Bispo TR, Rodart IF, Steinmetz L, Miachon AAS, Spinola E Castro AM, Damiani D, Kochi C, Longui CA. The Use of miRNA Panel as a Growth Plate Marker of Short-Term Response to GH. Clin Endocrinol (Oxf). 2025 Sep;103(3):327-337. doi: 10.1111/cen.15278. Epub 2025 May 20.

  PMID: 40394920 DERIVED

Central Study Contacts

Carlos A Longui, MD

CONTACT

55-11-983266815; carloslongui@msn.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: July 7, 2023
• First Posted: July 14, 2023
• Study Start: June 1, 2023
• Primary Completion: June 3, 2024
• Study Completion: June 15, 2025
• Last Updated: July 14, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)