GHD Reversal Trial Overview

Full Title 

The GHD 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.

The aim of the GHD Reversal Trial is to assess the clinical and cost effectiveness of stopping growth hormone vs continuing growth hormone in children with early Growth Hormone Deficiency reversal. 

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LATEST NEWS

The second patient was randomised to the GHD Reversal Trial on the 8th February 2024!  Many congratulations to all of the team at Nottingham University Hospitals NHS Trust for this wonderful achievement.  As of the end of February 2024, we have 14 sites open to recruitment (10 in the UK and four in Austria)!   Set up is in progress at a further five UK NHS Trusts and one Austrian centre. 

Non-substantial amendment 03 was released to sites on the 20th February 2024.  This included an update to the trial protocol (v4.0) to allow for glucagon as a permitted growth hormone test, and clarification of the expected procedure for height measurement.  The information sheets and case report forms have been updated to reflect these changes.

We would like to thank all of our collaborators for their continued support of the trial, it is very much appreciated.

 

Design

The GHD Reversal Trial is a multicentre, open-label, randomised controlled non-inferiority trial.   It includes an internal pilot study, qualitative sub-study and a within-trial cost-effectiveness analysis.  Participants will be randomised in a 1:1 ratio to either stop growth hormone therapy (GH-) or continue treatment (GH+).  138 participants will be randomised over 3.5 years.

Aims of the Trial

  1. To assess whether children with early Growth Hormone Deficiency (GHD) reversal who stop growth hormone therapy (GH-) achieve no worse Final Height Standard Deviation Scores (primary outcome), Target Height minus Final Height, Health Related Quality of Life, bone health index and lipid profiles (secondary outcomes) than those continuing growth hormone (GH+).
  2. To determine the cost-effectiveness of GH- in the early re-testing scenario, and the cost-effectiveness of the new care pathway (early re-testing) compared to traditional care (late re-testing).
  3. To assess staff, parent and patient perspectives of the trial pathways and reasons for declining to participate or dropping-out of the trial.

Setting

Suitable patients will be identified from 12 UK NHS Trusts and 5 Austrian paediatric endocrine centres.

Target Population

Children with reversed idiopathic, isolated growth hormone deficiency (I-GHD) and normal brain MRI (including small anterior pituitary) in established puberty (Tanner stages B2/3 & P2/3 in girls, P2/3 & 6-12ml testes in boys). 

Intervention

Participants will be randomised to either stop growth hormone therapy (GH-) or continue growth hormone therapy (GH+).

Measurement of outcomes

Primary Outcome

  • Final height in standard deviation score (SDS)

Secondary Outcomes: Growth Related

  • The proportion of children reaching normal adult height (0 +/- 2SD)
  • The proportion reaching mid-parental target height (0 +/- 2SD)
  • Difference in target height minus final height (SDS/cm)

Secondary Outcomes: Bone Related (using Bone Xpert software)

  • Bone age delay at final height
  • Bone age acceleration from enrolment to final height
  • Bone health index at final height

Secondary Outcomes: Biochemistry

  • Serum IGF-1 and lipid profiles (fasting lipids- serum triglyceride and serum total cholesterol) at final height
  • Peak stimulated growth hormone (GH) at final height

Secondary Outcomes: Other

  • Adverse events

Secondary Outcomes: Health Economics

  • Cost per percentage of children in each arm achieving target height
  • Cost per quality adjusted life year (QALY) gained using the Child Health Utility-9D

Secondary Outcomes: Qualitative Research (sub-study)

  • Trial acceptability (parents, participants and site staff)
  • Reasons for declining participation in the trial
  • Parent and patient experience of the trial and treatment pathways

Further Information...

Co-Chief Investigator (UK): 

Professor Mehul Dattani, Institute of Child Health, University College London

Co-Chief Investigator (Austria): 

Professor Wolfgang Högler,  Department of Paediatrics and Adolescent Medicine, Kepler Universitätsklinikum

Trial Sponsor: 

University College London

Funding: 

National Institute for Health Research Health Technology Assessment (NIHR127468)

EudraCT Number: 

2020-001006-39

MHRA CTA:

20363/0440/001-0001

Research Ethics Committee:

Wales REC 3

REC Reference Number:

22/WA/0005

ISRCTN:

ISRCTN12552768

CPMS ID: 

51704

EU CT:

2022-502008-62-00