Clinical Research Studies

Title of Protocol A clinical study to assess whether the gut microbiome affects the response of children with short stature (SS) to GH therapy Research questions: • Does the composition of the gut microbiome of SS children differ from their “normal” siblings or age/sex-matched controls (with normal height 10-90%) ? • Does the composition of the gut microbiome change in response to GH therapy? • Can the initial composition of the gut microbiome predict response to therapy? Background and significance: Short stature (SS) is defined as a standing height below 2 SDS for sex/age matched controls of a well-nourished subject. Short stature can be due to various causes such as growth hormone deficiency (GHD), syndromes or idiopathic short stature (ISS). The Utah Growth Study (1), which is the largest population-based survey of growth in nearly 115,000 American children, found that approximately 44,000 children in the US have SS (2). SS children can be treated with rhGH till attainment of final adult height prediction. The response to GH therapy usually assessed every 3-4 months during therapy (3). GH usually improves growth velocity and final height in SS children, however the response varies greatly (4). In the past few years there is an increasing rate of poor or unsatisfactory response to GH treatment among SS subjects (i.e., not leading to significant catch-up growth) (5). The reasons for the variable response are not clear. GH dosing is weight based and monitoring and dose adjustments are based on blood tests and growth. Using data from the Genentech National Cooperative Growth Study (NCGS), collected over a 25-year period, to examine the responsiveness to rhGH in1,186 SS patients it was found that during the first year, lower BMI SDS predicted worse response to GH therapy (6).This data are in line with a previous report showing that children with SS have lower BMI than children in the normal population (7).