Plain English Summary
Not provided at time of registration
Trial website
Additional identifiers
EudraCT number
2005-001507-19
ClinicalTrials.gov number
Protocol/serial number
2261
Study information
Scientific title
A randomized, multicentre, multinational trial to evaluate the safety and efficacy of Growth Hormone treatment at varying doses in short children, born small for gestational age (SGA)
Acronym
NESGAS
Study hypothesis
Several companies were recently awarded a product licence for the treatment with high dose growth hormone (GH) of short children born small for gestational age without based on two large studies showing improvements in final height. The recommended dose of growth hormone was 35 µg/kg/day but the product license also acknowledged that a larger dose of 67 µg/kg/day could be used during the first year of treatment to enhance catch-up growth. In the USA the larger dose is used routinely as approved by the FDA.
The British Society for Paediatric Endocrinology and Diabetes (BSPED), which represents consultants in the UK who prescribe growth hormone therapy, had concerns about the widespread use of GH in this indication without further study. In particular they were concerned that the use of the lower dose during the first year of treatment may lead to many non-responders to GH staying on treatment for much longer than necessary. Secondly they had concerns about whether the long term safety of the therapy had been proven and they wanted to gather further information on carbohydrate metabolism and levels of insulin-like growth factor 1 in the circulation. The Society felt that such information should be gathered for the likely NICE review, of this and other indications for GH therapy.
The novel features of the study are:
1. All subjects will be treated with the high dose of GH during the first year to identify responders from non-responders. Non-responders to the high dose of GH would not continue with GH therapy beyond the first year.
2. That all patients would have careful assessments of carbohydrate metabolism before starting treatment and would continue to be assessed annually with glucose tolerance tests and studies of body composition once treatment had started
3. All the children would have IGF-1 levels carefully monitored to determine the effects of different dosages and whether variable dose in the second year could lead to improved growth
Ethics approval
Eastern Multicentre Research Ethics Committee (now Cambridgeshire 4 REC), 10/06/2004, ref: 04/5/025
Study design
Randomised interventional treatment trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details listed on the study web page to request a patient information sheet: http://www.medschl.cam.ac.uk/paediatrics/pages/nesgas.html
Condition
Topic: Medicines for Children Research Network; Subtopic: All Diagnoses; Disease: All Diseases
Intervention
All study participants were treated with 67 µg/kg/day growth hormone in the first year of the study to identify non-responders from responders. Non-responders would not continue with growth hormone treatment beyond the first year. Responders would be randomised to receive a dose of 35 µg/kg/day, 67 µg/kg/day or an IGF-1 titrated dose for the following 2 years at the end of which all study participants change to a dose of 35 µg/kg/day which they would continue to take until final height.
Follow up length: 60 months. Initially patients were followed up for 3 years, an amendment has now been approved to follow up participants who consent to participate in NESGAS Extension until they reach final height.
Study Entry: registration and one or more randomisations
Recruitment: Recruitment is now complete and total UK recruitment was 34 patients however lower dropout rates than anticipated mean that there are sufficient recruits for the study data to be statistically valid.
Intervention type
Drug
Phase
Not Applicable
Drug names
Growth hormone
Primary outcome measure
Height gain (HSDS) (3 yrs), measured when study participants reach final height; this has been taken to be 16 years of age at the latest some participants will reach final height before that age.
Secondary outcome measures
1. Insulin resistance (IVGTT)
2. IGF-related parameters
3. Genetic polymorphisms in the population
Measured when study participants reach final height; this has been taken to be 16 years of age at the latest some participants will reach final height before that age.
Overall trial start date
30/09/2004
Overall trial end date
31/12/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Small for gestational age (body weight [BW] less than -2 SD according to country specific references)
2. Gestational age at birth more than 28 weeks
3. Short at 4 years of age (Height SDS less than -2.5 according to country specific references)
4. Short for parental height (HSDS greater than 1 SD below parental adjusted HSDS (mid parental height SDS)
5. Age 4 - 8.99 years (girls) and 4 - 9.99 years (boys)
6. Prepubertal at start of treatment (largest testis volume less than 4 ml, breast stage 1)
7. Height records must be available for 6 months prior to inclusion into the study
8. Height velocity SDS less than 0 during last 6 months (according to country specific references)
9. Subjects must be naïve to growth hormone therapy
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
Planned Sample Size: 100; UK Sample Size: 34
Participant exclusion criteria
1. Known or suspected allergy to growth hormone
2. Previous participation in growth hormone trial
3. Severe mental retardation as judged by the investigator
4. Previous or active malignancy
5. Benign intracranial hypertension (present or past)
6. Diabetes
7. Growth retardation due to chronic diseases, syndromes (like FAS) and chromosomal anomalies (except for Silver Russell syndrome)
8. Psychological problems likely to lead to significant non-compliance
Recruitment start date
30/09/2004
Recruitment end date
31/12/2008
Locations
Countries of recruitment
Ireland, United Kingdom
Trial participating centre
Department of Child Health
Glasgow
G3 8SJ
United Kingdom
Sponsor information
Organisation
Rigshospitalet (Denmark)
Sponsor details
Blegdamsvej 9
Copenhagen
2100
Denmark
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Research organisation
Funder name
British Society of Paediatric Endocrinology and Diabetes (BSPED) (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23860366
Publication citations
-
Results
Jensen RB, Thankamony A, O'Connell SM, Salgin B, Kirk J, Donaldson M, Ivarsson SA, Söder O, Roche E, Hoey H, Dunger DB, Juul A, , Baseline IGF-I levels determine insulin secretion and insulin sensitivity during the first year on growth hormone therapy in children born small for gestational age. Results from a North European Multicentre Study (NESGAS)., Horm Res Paediatr, 2013, 80, 1, 38-46, doi: 10.1159/000353438.