Small for Gestational Age
Conditions
Keywords
Small for gestational age, insulin sensitivity, IGF-1 response, growth hormone treatment
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.
Interventions
DRUGMetformin
Metformin is administered as an oral solution
DRUGGrowth Hormone
Growth Hormone- no specific band
DRUGPlacebo
Sponsors
Rigshospitalet, Denmark
Birmingham Women's and Children's NHS Foundation Trust
The National Children's Hospital, Tallaght
Cambridge University Hospitals NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to 10 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IGF-1 response | 6 months | Area under the curve of IGF-1 standard deviation scores over 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Height velocity | 6 months and 1 year | Height increments |
| Insulin sensitivity | 6 months and 1 year | Measured by homeostasis model assessment model |
| Insulin secretion | 6 months | Measured by oral glucose tolerance test |
Contacts
Primary ContactDavid B Dunger, MD
Outcome results
None listed