Use of miRNAs in Growth Hormone Deficiency (GHD) (GH-miRNA2)

New Potential Biomarkers for Diagnosis of Growth Hormone (GH) Deficiency and Early Assessment of Response to GH Treatment for Appropriate Personalization of Therapy

This study aims at improving knowledge about the diagnosis of growth hormone deficiency (GHD) and treatment with growth hormone (GH), with the goal of providing information on the presence of new biomarkers, such as miRNAs, for diagnostic and therapeutic purposes, with the goal of establishing a personalized GH treatment scheme, optimizing resources, reducing costs, and improving outcomes.

Study Overview

• Status: Recruiting
• Conditions: Growth Hormone Deficiency

Detailed Description

In 200 prepubertal and pubertal subjects with the suspicion of GHD, the levels of three specific circulating miRNas will be measured to establish whether they can be used for the diagnosis of GH deficiency. In subjects with isolated idiopathic GHD (IIGHD), short statured patients born SGA, Noonan and Turner syndromes, and SHOX deficiency, we will also assess the changes of the identified miRNAs before and after 3 months on GH therapy to verify an early growth prediction model for growth response at 12 months on treatment. Finally, we plan to identify any differences in these miRNAs at 3 months on treatment using daily GH versus weekly (long-acting) GH.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Maria E Street, MD, PhD; Phone Number: +39 0521 033557; Email: mariaelisabeth.street@unipr.it

Study Locations

• Italy
  • Emilia Romagna
    • Parma, Emilia Romagna, Italy, 43121
      • Recruiting
      • University of Parma
      • Contact: Maria E Street; Phone Number: +39 0521 033557; Email: mariaelisabeth.street@unipr.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients will be investigated in routine practice during the normal workup for short stature and stunted growth. Treatment will be also delivered accordind to standard care indications and as established by regulatory agencies in Italy.

Description

Inclusion Criteria for aim 1:

• Children with short stature and suspicion of GHD
• Subjects with organic GH deficiency

Exclusion criteria for aim 1:

-Subjects with underlying genetic conditions and chronic diseases

Inclusion Criteria for aim 2-3-5:

• patients having confirmed GHD enrolled for aim 1
• patients with growth failure and born SGA (>4 yr of age)
• patients with Noonan and Turner syndrome and growth failure
• patients with short stature homeobox-containing gene deficiency (SHOXD) and growth failure

Inclusion Criteria for aim 4:

- Isolated idiopathic prepubertal naive GHD subjects on long-acting versus daily GH therapy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessing new biomarkers for the diagnosis of GHD	The 1st objective will consist in the enrolment of 200 subjects, nationwide, undergoing standard routine work-up for the diagnosis of GHD. The specific miRNAs will be measured at the time of both stimulation tests in order to include subjects with both confirmed and unconfirmed GHD and guarantee reproducibility; in addition, subjects with organic GH deficiency will be included.	3 years
Measuring miRNA changes after 3 months on GH therapy	The 2nd objective will consist in measuring these specific miRNAs before and at 3 months on treatment in 200 subjects with isolated idiopathic GHD(IIGHD), and in 60 short statured patients born SGA, in 60 having Noonan and Turner syndromes, and in 30 with SHOX deficiency, according to current indications to verify whether changes are confirmed in pubertal versus prepubertal subjects and in conditions other than IIGHD.	3 years
Multiple linear regression models	The 3rd objective will consist in investigating the major determinants of height variations between 0 and 6 months, 0 and 12 months and the variance of growth rate variation between 0 and 6 months including the levels and/or changes in the specific miRNAs at baseline and at 3 months on treatment by using multiple linear regression models to establish early prediction models of growth response..	3 years
Measuring miRNA changes between daily and long-acting GH therapy	The 4th objective will consist in measuring these specific miRNAs before and at 3 months on treatment in children with IIGHD being treated with daily versus longacting GH. Findings will be compared with those in the IIGHD group receiving daily GH treatment as an exploratory task, thus, only a small number of subjects will be enrolled, and anyway as many as possible.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sex-specific miRNA changes after 3 months on long-acting GH therapy	Any differences between males and females in miRNAs expression after 3 months of long-acting GH therapy will be evaluated.	3 years

Collaborators and Investigators

• Sponsor: University of Parma
• Collaborators: IRCCS Azienda Ospedaliero-Universitaria di Bologna; Federico II University; University of Campania "Luigi Vanvitelli"; Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; Istituto Auxologico Italiano; Azienda Unita Sanitaria Locale Reggio Emilia; Azienda Ospedaliera Universitaria Policlinico "G. Martino"; Università degli Studi del Piemonte Orientale "Amedeo Avogadro"; Azienda Unita Sanitaria Locale di Piacenza; Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari; Ospedali Riuniti Ancona; Ospedali Riuniti di Foggia; OSPEDALE CARLO POMA ASST MANTOVA; IRCCS Ospedale San Raffaele; Azienda Ospedaliero Universitaria Policlinico Modena
• Investigators: Principal Investigator: Maria E Street, MD, PhD, University of Parma

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2023
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: June 6, 2024
• First Submitted That Met QC Criteria: June 6, 2024
• First Posted (Actual): June 13, 2024

Study Record Updates

• Last Update Posted (Actual): June 13, 2024
• Last Update Submitted That Met QC Criteria: June 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: miRNA; growth hormone; growth hormone deficiency; growth hormone treatment; Turner syndrome; small for gestational age; Noonan syndrome; SHOX deficiency
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Pituitary Diseases; Dwarfism; Bone Diseases, Developmental; Hypopituitarism; Dwarfism, Pituitary; Endocrine System Diseases
• Other Study ID Numbers: 821/2022/OSS/UNIPR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No