Metformin SGA study version 1.2
Research type
Research Study
Full title
Effect of insulin sensitization on insulin like growth factor-1 responses to growth hormone treatment in children born small for gestational age
IRAS ID
197289
Contact name
Ajay Thankamony
Contact email
Sponsor organisation
Cambridge University Hospitals
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
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), a growth promoting hormone and the most important circulating mediator of GH action may underpin this heterogeneity. We recently reported that variants in the genes related to lower insulin sensitivity are associated with reduced IGF-1 and growth response to GH therapy in SGA children. We hypothesise 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, we aim to study 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 4 paediatric endocrine units in Denmark, Ireland and UK. 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. They will receive GH treatment for the entire duration of the study (12 months). They 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 1-3 monthly measurements of height, weight and skinfold thickness, hormones and safety measures. 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.REC name
East of England - Cambridge South Research Ethics Committee
REC reference
16/EE/0315
Date of REC Opinion
5 Oct 2016
REC opinion
Further Information Favourable Opinion