Condition category
Pregnancy and Childbirth
Date applied
23/04/2010
Date assigned
23/04/2010
Last edited
11/07/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.medschl.cam.ac.uk/paediatrics/pages/nesgas.html

Contact information

Type

Scientific

Primary contact

Ms Emma-Jane Gault

ORCID ID

Contact details

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

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 measures

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

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

http://www.rigshospitalet.dk/RHenglish/Menu/

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

Results - basic reporting

Publication summary

2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23860366

Publication citations

  1. 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.

Additional files

Editorial Notes