Effect of Insulin Sensitization on IGF-1 Response to Growth Hormone in SGA Children

NCT ID: NCT02931591

Last Updated: 2016-10-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2020-06-30

Brief Summary

This study is aimed to determine if Metformin treatment in children born small for gestational age (SGA) who are being treated with Growth Hormone (GH) for short stature improves the response to GH by producing greater concentrations of Insulin-like growth factor -1 (IGF-1) in the blood.

Detailed Description

Growth hormone treatment (GH) is recommended in children born small for gestational age (SGA) who fail to catch-up. SGA is a heterogeneous condition as reflected in the varied response to GH treatment. Variable generation and resistance to Insulin-like growth factor-1 (IGF-1), the most important circulating mediator of GH action may underpin this heterogeneity. An association between the variants in the genes related to lower insulin sensitivity and reduced IGF-1 and growth response to GH therapy in SGA children have been reported recently. The hypothesis of this study is that insulin sensitivity may be causally linked to the response to GH therapy, and adjuvant therapy with an insulin sensitizer may improve IGF-1 generation, decrease IGF-I resistance and optimise growth response.

To explore this hypothesis, this study aims to determine the effects of insulin sensitization using Metformin as an adjuvant to a fixed dose GH therapy for 6 months in short SGA children. The patients will be short SGA children between age 4 -10 years and identified from three paediatric endocrine units in Denmark, Ireland and the United Kingdom. In this mechanistic study 24 subjects starting GH treatment will be randomised in a 1:1 ratio to adjunctive Metformin or placebo for 6 months and followed-up for another 6months. The participants will receive GH treatment for the entire duration of the study (12 months) and will undergo an oral glucose tolerance test and dual-energy x-ray absorptiometry scan to determine glucose metabolism and body fat mass respectively at baseline and 6 months, and will have 3 monthly measurements of height, weight and skinfold thickness. The primary outcome will be the area under the curve of IGF-1 levels measured at 0, 1, 3 and 6 months. Secondary outcomes will include changes in insulin sensitivity, height, body fat mass and safety measures at 6 and 12 months.

Conditions

Small for Gestational Age

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

GH+Metformin

The children will be given both Growth Hormone and Metformin for 6 months

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Metformin is administered as an oral solution

Growth Hormone

Intervention Type: DRUG

Growth Hormone- no specific band

GH+Placebo

Children will be given both GH and Placebo for 6 months

Group Type: PLACEBO_COMPARATOR

Growth Hormone

Intervention Type: DRUG

Growth Hormone- no specific band

Placebo

Intervention Type: DRUG

Interventions

Metformin

Metformin is administered as an oral solution

Intervention Type: DRUG

Growth Hormone

Growth Hormone- no specific band

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• SGA children eligible for GH treatment according to European Medicines Agency (EMA) and The National Institute for Health and Care Excellence (NICE) criteria
• Gestational age at birth >28 weeks
• Age 4-9 years in girls and 4-10 years in boys
• Prepubertal at start of treatment
• Naïve to GH therapy

Exclusion Criteria

• Known or suspected allergy to GH
• Previous participation in a GH trial
• Severe learning difficulties
• Previous or active malignancy
• Benign intracranial hypertension

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rigshospitalet, Denmark

OTHER

Sponsor Role: collaborator

Birmingham Women's and Children's NHS Foundation Trust

OTHER

Sponsor Role: collaborator

The National Children's Hospital, Tallaght

OTHER

Sponsor Role: collaborator

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

David B Dunger

Professor of Paediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

David B Dunger, MD

Role: CONTACT

dbd25@cam.ac.uk

+441223 762944

Other Identifiers

SGA Metformin Study

Identifier Type: -

Identifier Source: org_study_id