The IIH-Advance study
About the study
The optimal method to achieve and maintain weight loss and disease remission in IIH is not known. This trial will use the new effective and safe anti-obesity drug Tirzepatide to induce weight loss, and will evaluate the potential impact of weight maintenance and weight regain on IIH.
Aim and objectives
The aim of the trial is to evaluate the clinical impact of weight change induced by Tirzepatide in IIH.
Primary Objective
To evaluate the effect of weight loss induced by Tirzepatide plus standard of care over 6 months in patients diagnosed with IIH compared to standard of care only on proportion with resolution of papilloedema, measured by OCT.
Secondary Objectives
To determine the effect of weight loss induced by Tirzepatide plus standard of care over 6 months in patients diagnosed with IIH compared to standard of care on change in:
- Clinical outcomes: Papilloedema, headache, weight and body mass index
- Patient-centred outcomes: Health- and vision- related quality of life, binge eating, alcohol use, anxiety and depression, tolerability of weight loss in IIH driven by Tirzepatide determined by all cause discontinuation
- Economic outcomes: Service use, absenteeism and presenteeism, medication use (use and dose of acetazolamide or other ICP lowering drugs)
Current enrolment curve
Recruitment target: 88
Information about the Study
Study Design
IIH-Advance is a pragmatic, unblinded, 2-arm, multi-stage randomised controlled trial of patients with active IIH. The trial will compare participants expected to achieve significant weight loss (driven by Tirzepatide, an anti-obesity drug) with participants receiving standard of care. There will be 3 stages in the IIH-Advance trial.
Setting
Participants from across the UK will be recruited through direct patient-initiated contact with the trial researchers. The intervention will be delivered at participants’ homes and papilloedema measured by OCT at a third-party high street optician, Specsavers. Outcome measures will be collected directly via participant reported outcome measures administered online, and by video calls between participant and researcher.
Sub-studies
A mechanistic substudy will collect biofluids (saliva, blood, urine and stool) for evaluation of liver function, diabetic status, hormones, markers of inflammation, pain chemicals involved in headache, and micoRNA. Stool samples will be collected to evaluate the gut microbiome. Samples will be collected at baseline, 3 and 6 months.
Participant population and sample size
88 adults with active IIH.
Interventions
Tirzepatide once weekly via a subcutaneous injector pen plus standard of care vs standard of care alone.
Study Funders
The study is funded by the Sir Jules Thorn Charitable Trust. The sponsor is the University of Birmingham.
Chief Investigator
Professor Sinclair is the Professor of Neurology at the University of Birmingham, specialising in Idiopathic Intracranial Hypertension (IIH).
Her research focuses on understanding the causes of IIH and developing new treatments. Professor Sinclair made the original discovery of the use of GLP-1 receptor agonists to lower intracranial pressure and pioneered the pre-clinical work and initial trials in IIH. In addition to her academic role, she works as a consultant neurologist at University Hospital NHS Foundation Trust, UK, where she collaborates closely with the headache service. She was previously the patron of the patient charity IIH UK and continues to work closely with patient groups, using her research to bring meaningful benefits to patients with IIH.
