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

Effect of Insulin Sensitization on Insulin Like Growth Factor-1 Responses to Growth Hormone Treatment in Children Born Small for Gestational Age

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.

Study Overview

• Status: Unknown
• Conditions: Small for Gestational Age
• Intervention / Treatment: Drug: Placebo; Drug: Metformin; Drug: Growth Hormone

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.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: David B Dunger, MD; Phone Number: +441223 762944; Email: dbd25@cam.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: GH+Metformin; The children will be given both Growth Hormone and Metformin for 6 months	Drug: Metformin; Metformin is administered as an oral solution; Drug: Growth Hormone; Growth Hormone- no specific band
Placebo Comparator: GH+Placebo; Children will be given both GH and Placebo for 6 months	Drug: Placebo; Drug: Growth Hormone; Growth Hormone- no specific band

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IGF-1 response	Area under the curve of IGF-1 standard deviation scores over 6 months	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Height velocity	Height increments	6 months and 1 year
Insulin sensitivity	Measured by homeostasis model assessment model	6 months and 1 year
Insulin secretion	Measured by oral glucose tolerance test	6 months

Collaborators and Investigators

• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Collaborators: Rigshospitalet, Denmark; Birmingham Women's and Children's NHS Foundation Trust; The National Children's Hospital, Tallaght

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Anticipated): November 1, 2019
• Study Completion (Anticipated): June 1, 2020

Study Registration Dates

• First Submitted: September 14, 2016
• First Submitted That Met QC Criteria: October 11, 2016
• First Posted (Estimate): October 13, 2016

Study Record Updates

• Last Update Posted (Estimate): October 14, 2016
• Last Update Submitted That Met QC Criteria: October 12, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: insulin sensitivity; Small for gestational age; IGF-1 response; growth hormone treatment
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Metformin; Hormones
• Other Study ID Numbers: SGA Metformin Study

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
• product manufactured in and exported from the U.S.: No