The safety and efficacy of growth hormone treatment in children born small for gestational age

ISRCTN ISRCTN36828561
DOI https://doi.org/10.1186/ISRCTN36828561
EudraCT/CTIS number 2005-001507-19
Secondary identifying numbers 2261
Submission date
23/04/2010
Registration date
23/04/2010
Last edited
11/07/2014
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Pregnancy and Childbirth
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Study website

Contact information

Ms Emma-Jane Gault
Scientific

Department of Child Health
Dalnair Street
Glasgow
G3 8SJ
United Kingdom

Study information

Study designRandomised interventional treatment trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant 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
Scientific titleA 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)
Study acronymNESGAS
Study objectivesSeveral 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(s)Eastern Multicentre Research Ethics Committee (now Cambridgeshire 4 REC), 10/06/2004, ref: 04/5/025
Health condition(s) or problem(s) studiedTopic: Medicines for Children Research Network; Subtopic: All Diagnoses; Disease: All Diseases
InterventionAll 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Growth hormone
Primary outcome measureHeight 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 measures1. 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 study start date30/09/2004
Completion date31/12/2008

Eligibility

Participant type(s)Patient
Age groupChild
Lower age limit4 Years
Upper age limit9 Years
SexBoth
Target number of participantsPlanned Sample Size: 100; UK Sample Size: 34
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment30/09/2004
Date of final enrolment31/12/2008

Locations

Countries of recruitment

  • Ireland
  • Scotland
  • United Kingdom

Study participating centre

Department of Child Health
Glasgow
G3 8SJ
United Kingdom

Sponsor information

Rigshospitalet (Denmark)
Hospital/treatment centre

Blegdamsvej 9
Copenhagen
2100
Denmark

Website http://www.rigshospitalet.dk/RHenglish/Menu/
ROR logo "ROR" https://ror.org/03mchdq19

Funders

Funder type

Research organisation

British Society of Paediatric Endocrinology and Diabetes (BSPED) (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/01/2013 Yes No