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

Small for Gestational Age Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02931591
• Other study ID #: SGA Metformin Study
• Status: Not yet recruiting
• Phase: N/A
• First received: September 14, 2016
• Last updated: October 12, 2016
• Start date: November 2016
• Est. completion date: June 2020

Study information

• Verified date: October 2016
• Source: Cambridge University Hospitals NHS Foundation Trust
• Contact: David B Dunger, MD
• Phone: +441223 762944
• Email: dbd25[@]cam.ac.uk
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: June 2020
• Est. primary completion date: November 2019
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years to 10 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Small for Gestational Age

Intervention

Drug:
• Metformin
Metformin is administered as an oral solution
• Growth Hormone
Growth Hormone- no specific band
• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Cambridge University Hospitals NHS Foundation Trust	Birmingham Children's Hospital NHS Foundation Trust, Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark, The National Children's Hospital, Tallaght

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IGF-1 response	Area under the curve of IGF-1 standard deviation scores over 6 months	6 months	No
Secondary	Height velocity	Height increments	6 months and 1 year	No
Secondary	Insulin sensitivity	Measured by homeostasis model assessment model	6 months and 1 year	No
Secondary	Insulin secretion	Measured by oral glucose tolerance test	6 months	No