The GHD Reversal Trial
Research type
Research Study
Full title
The Growth Hormone Deficiency Reversal Trial: Effect on final height of discontinuation vs continuation of growth hormone treatment in pubertal children with isolated growth hormone deficiency – A non-inferiority randomised controlled trial
IRAS ID
281209
Contact name
Mehul Dattani
Contact email
Sponsor organisation
University College London
Eudract number
2020-001006-39
ISRCTN Number
ISRCTN12552768
Duration of Study in the UK
7 years, 5 months, 30 days
Research summary
Research Summary
Growth hormone (GH) is a hormone essential for normal growth and development. If a child doesn’t have enough GH, the speed of growth is slower and final adult height reduced. Growth hormone deficiency (GHD) is a condition where the pituitary gland doesn’t make enough growth hormone in childhood. GH treatment allows children with GHD to grow normally. GH is given as daily injections continued until the child reaches adult height. GH is usually given for 5-10 years and can cost £10,000-23,000 per patient per year.
Children are tested for GHD by measuring the highest amount of GH in the blood following a test. When GH production is checked after children reach their final height, some children are found to have normal levels of GH; these children therefore no longer have GHD. Some doctors think that this change occurs during puberty. Therefore, many pubertal children on GH therapy are assumed to no longer have GHD but doctors usually continue daily GH injections until the child reaches final adult height. Therefore some children continue to have potentially unnecessary, costly daily injections.
The aim of this ‘GHD reversal’ study is to find out whether certain children can stop their GH injections at puberty and still reach a similar final adult height to those children who continue to have daily GH injections. 138 children with GHD from 16 hospitals whose stimulated GH levels are found to be normal when tested after they have entered puberty, will take part in this study. After giving their consent, these children will be randomised (chosen by 50:50 chance by a computer) to either continue or stop their daily GH injections. The study will test whether the children who stop their GH injections reach a similar final adult height to those children that continue their injections.
Summary of Results
GHD Lay Results Summary
The GHD Reversal Study: Why did we need it?
The GHD Reversal Study looked at children with growth hormone deficiency (GHD) to see if they still needed growth hormone (GH) injections after they reached puberty. The study was initiated because many children with GHD are found to have normal GH levels once they reach their final adult height, which suggests that the condition may have reversed itself during puberty, when the sex hormone levels normally increase and in turn lead to increased growth hormone levels. Continuing daily GH injections is unpleasant and inconvenient for children, expensive for the NHS, and could have potential side effects.
The goal of the study was to find out if children whose GHD had reversed could stop taking GH injections without affecting their final height, compared to those who continued taking injections. The study was also meant to look at the cost-effectiveness of this approach and the perspectives of families and staff.The GHD Reversal Study: How we did it and what did we find?
The study, which included 15 hospitals from the UK and Austria, aimed to recruit 138 children. However, due to several challenges, only 5 children were enrolled. We found, however, that 40-50% of retested children had a reversal of their GHD.
The study's findings highlighted some issues that prevented a full-scale randomised trial:
* Hospitals found it difficult to change their standard procedures to allow for early retesting of GHD in children.
* When early retesting was introduced some doctors and parents were reluctant to continue GH treatment or did not want to randomise children between stopping or continuing GH if the child's GHD had reversed.
* Other children and families were reluctant to give up the medication because of the initial difficulty they had in getting the diagnosis and treatment.
Because of the low number of participants, the study could not answer its main questions.The GHD Reversal Study: What is happening now?
To continue this research, hospitals in Austria and Italy will conduct an observational study. This study will look at existing data from children with GHD reversal to see if those who stop treatment reach a final height similar to those who continue. While not as strong as a randomised study, this research will still provide valuable information.The GHD Reversal Study: Thank you!
Thank you to everyone who was involved in the GHD reversal study in the UK and Austria, including the clinical and research staff. Most importantly, we thank the children, young people, and their families for their participation and contribution.REC name
Wales REC 3
REC reference
22/WA/0005
Date of REC Opinion
8 Mar 2022
REC opinion
Further Information Favourable Opinion