IIH-Advance: A randomised clinical trial to determine the effects of weight loss, induced by a weight loss drug (Tirzepatide), in adults with active idiopathic intracranial hypertension
| ISRCTN | ISRCTN22446424 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN22446424 |
| Sponsor | University of Birmingham |
| Funder | Sir Jules Thorn Charitable Trust |
- Submission date
- 15/01/2026
- Registration date
- 19/01/2026
- Last edited
- 15/01/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Idiopathic Intracranial Hypertension (IIH) is a condition where pressure inside the skull becomes too high. It mainly affects women of childbearing age who have obesity. This pressure can cause swelling at the back of the eye (called papilloedema), severe headaches, and sometimes permanent vision loss. There is no approved medicine for IIH, and current treatments are difficult to manage. Losing weight can help reduce the pressure and improve symptoms, but dieting is hard to maintain and surgery is not suitable for everyone. New medicines that help with weight loss, such as Tirzepatide, may offer a safer and easier option. This study aims to find out if Tirzepatide can help people with IIH by reducing weight and improving eye health.
Who can participate?
Adults aged 18 or over who have a confirmed diagnosis of IIH and swelling at the back of the eye (papilloedema) can take part. Participants need to have a body mass index (BMI) of 30 or more, or 27 or more if they have IIH linked to weight gain or belong to certain ethnic groups. They must have tried and failed to lose weight through dieting before. People who are pregnant, breastfeeding, have had certain surgeries, or have specific medical conditions cannot take part.
What does the study involve?
Participants will be randomly assigned to one of two groups. One group will receive Tirzepatide once a week using an injection pen, along with standard care. The other group will receive standard care only. The treatment will last for six months. Participants will give consent, self-administer the medication at home, and have their eye health checked using a scan called Optical Coherence Tomography (OCT) at a local Specsavers optician.
What are the possible benefits and risks of participating?
The main potential benefit is that weight loss from Tirzepatide may reduce the pressure inside the skull, improve eye health, and reduce headaches. However, there are risks, including possible side effects from the medication such as nausea or other health issues. There is also a chance that symptoms may return if weight is regained after stopping the medication.
Where is the study run from?
University of Birmingham (UK), with eye scans carried out at Specsavers opticians.
When is the study starting and how long is it expected to run for?
January 2026 to October 2028
Who is funding the study?
Sir Jules Thorn Charitable Trust (UK)
Who is the main contact?
Prof Alexandra Sinclair, a.b.sinclair@bham.ac.uk
Lauren Sturdy, l.sturdy@bham.ac.uk
Contact information
Principal investigator
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
 ORCID ID |
0000-0003-2777-5132 |
|---|---|
| Phone | +44 1214144081 |
| a.b.sinclair@bham.ac.uk |
Public, Scientific
Birmingham Clinical Trials Unit
Public Health Building (Y17)
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
| ORCID ID |
0009-0006-1614-2988 |
|---|---|
| Phone | +44 121 4158840 |
| l.sturdy@bham.ac.uk |
Study information
| Primary study design | Interventional | |
|---|---|---|
| Allocation | Randomized controlled trial | |
| Masking | Open (masking not used) | |
| Control | Active | |
| Assignment | Parallel | |
| Purpose | Health services research, Supportive care, Treatment | |
| Participant information sheet | 48844 IIH-Advance PIS v2.0 27.11.2025.pdf | |
| Scientific title | A phase III multi-stage randomised controlled trial to determine the effects of weight loss, induced by Tirzepatide, in adults with active idiopathic intracranial hypertension | |
| Study acronym | IIH-Advance | |
| Study objectives | 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 through the evaluation of the proportion of patients with resolution of papilloedema, measured by Optical Coherence Topography scan (OCT). | |
| Ethics approval(s) |
Approved 29/10/2025, London - Central REC (3rd Floor 3 Piccadilly Place, London Road, Manchester, M1 3BN, United Kingdom; +44 207 104 8115; londoncentral.rec@hra.nhs.uk), ref: 347499 | |
| Health condition(s) or problem(s) studied | Idiopathic intracranial hypertension | |
| Intervention | Design Overview IIH-Advance is a phase III, multi-stage, randomised controlled trial designed to evaluate whether weight loss induced by tirzepatide improves disease activity in adults with active idiopathic intracranial hypertension (IIH). The trial uses a pragmatic, real-world approach, reflecting NHS practice while maintaining rigorous scientific standards. Trial Structure The study employs a two-arm parallel-group design with three sequential stages over a maximum of 18 months per participant: Stage R1 (Months 0-6): Participants are randomised 1:1 to tirzepatide plus standard care or standard care alone. This stage addresses the primary hypothesis: whether tirzepatide-driven weight loss increases the proportion of patients achieving papilloedema resolution at six months. Stage R2 (Months 6-12): Response-adaptive re-randomisation evaluates maintenance vs withdrawal and delayed initiation: Responders to tirzepatide: continue vs stop treatment. Non-responders to standard care: start tirzepatide vs continue standard care. This stage explores whether continued treatment sustains remission and whether late initiation still confers benefit. Stage SA3 (Months 12-18): Open-label tirzepatide for participants who have not yet received it,enabling assessment of recurrence and delayed response. Population and Eligibility N=86 adults with confirmed IIH (papilloedema on OCT),BMI ≥30 kg/m² (or ≥27 kg/m² with additional criteria),and at least one failed dietary attempt. Exclusions include recent bariatric surgery, prior IIH surgery, current glucose-lowering medication, recent GLP-1RA use and contraindications to tirzepatide. Intervention Participants allocated to active treatment will self-administer weekly tirzepatide injections, escalating from 2.5 mg to 15 mg over six months, with adjustments for tolerability. Standard care follows UK IIH guidelines (weight advice ± ICP-lowering medications). Data Collection and Monitoring All trial procedures are remote: OCT scans at Specsavers. Monthly video follow-ups for weight checks, adherence and safety. Electronic data capture for questionnaires and diaries. Bio sample kits and actigraphy devices mailed to participants. | |
| Intervention type | Drug | |
| Phase | Phase III | |
| Drug / device / biological / vaccine name(s) | Tirzepatide | |
| Primary outcome measure(s) |
| |
| Key secondary outcome measure(s) | ||
| Completion date | 31/10/2028 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 99 Years |
| Sex | All |
| Target sample size at registration | 86 |
| Key inclusion criteria | 1. Confirmed diagnosis of IIH as defined by the IIH consensus criteria 2. Age 18 years or older 3. No evidence of sight-threatening papilloedema requiring urgent surgical intervention 4. Presence of papilloedema in at least one eye measured by OCT RNFL 5. Body Mass Index (BMI) greater than or equal to: • 30.0 kg/sqm or • 27.0 kg/sqm with IIH associated with increased weight or • 27.0 kg/sqm and of South Asian, Chinese, other Asian, Middle Eastern, Black African or African Caribbean ethnicity\* 6. At least one self-reported unsuccessful dietary effort to lose body weight 7. Able to provide written informed consent |
| Key exclusion criteria | 1. Previous bariatric surgery within the last 3 months or intention to undergo bariatric surgery during the trial 2. Previous surgery for IIH including optic nerve sheath fenestration, CSF shunting procedures, sub-temporal decompression and venous stenting 3. Using glucose-lowering medication 4. Currently taking or has received a GLP-1R agonist for any indication in the last 4 weeks 5. Previous or current pancreatitis 6. Contraindication to Tirzepatide (for example, previous or current medullary cancer, history of multiple endocrine neoplasia, active gall stones) 7. Current eating disorder requiring hospital intervention or treatment 8. Is unable to self-administer (or administer with carer support) the trial medication 9. Females of child-bearing potential only: • Pregnant (spot urine test will be performed before randomisation to rule out pregnancy) • Not willing to take highly effective contraceptive measures during the study intervention period AND for 5 weeks following the last trial medication dose • Not willing to stop breastfeeding once randomised into the trial |
| Date of first enrolment | 19/01/2026 |
| Date of final enrolment | 31/01/2027 |
Locations
Countries of recruitment
- United Kingdom
- England
- Northern Ireland
- Scotland
- Wales
Study participating centre
Birmingham
B15 2TT
England
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | Requests for data generated during this study will be considered by BCTU (via bctudatashare@contacts.bham.ac.uk). Data will typically be available within six months after the primary publication unless it is not possible to share the data (for example: the trial results are to be used as part of a regulatory submission, the release of the data is subject to the approval of a third party who withholds their consent, or BCTU is not the controller of the data). Only scientifically sound proposals from appropriately qualified Research Groups will be considered for data sharing. The request will be reviewed by the BCTU Data Sharing Committee in discussion with the Chief Investigator and, where appropriate (or in absence of the Chief Investigator) any of the following: the Trial Sponsor, the relevant Trial Management Group (TMG), and independent Trial Steering Committee (TSC). A formal Data Sharing Agreement (DSA) may be required between respective organisations once release of the data is approved and before data can be released. Data will be fully de-identified (anonymised) unless the DSA covers transfer of patient identifiable information. Any data transfer will use a secure and encrypted method. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 2.0 | 27/11/2025 | 15/01/2026 | No | Yes |
| Protocol file | version 1.0 | 03/09/2025 | 15/01/2026 | No | No |
Additional files
- 48844 IIH-Advance Protocol v1.0 03.09.2025.pdf
- Protocol file
- 48844 IIH-Advance PIS v2.0 27.11.2025.pdf
- Participant information sheet
Editorial Notes
NHW 15/01/2026: Trial's existence confirmed by London - Central REC.
