IIH Provoke: headache mechanisms in idiopathic intracranial hypertension
| ISRCTN | ISRCTN13251508 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13251508 |
| IRAS number | 307968 |
| Secondary identifying numbers | CPMS 52852, IRAS 307968 |
- Submission date
- 27/09/2022
- Registration date
- 24/10/2022
- Last edited
- 01/03/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
idiopathic intracranial hypertension (IIH) is a chronic condition of raised brain pressure occurring in young and often overweight women. Increasing numbers of women are diagnosed with IIH, along with the growing obesity epidemic. Patients can suffer blindness but a frequent debilitating issue is long-term, disabling headaches that diminish the quality of life in affected women. There are currently no specific treatments for IIH headaches, and understanding the underlying causes is limited. Our clinical work suggests that blocking calcitonin gene-related peptide (CGRP), which is a pain chemical, in IIH can improve headaches. Also, our previous research work has shown that glucagon-like peptide-1 receptor agonists can reduce brain pressure.
We aim to explore in detail the role of CGRP in IIH and use detailed physiological assessments in patients to gain an understanding of IIH headaches and potential drug targets. We also aim to evaluate if a glucagon-like peptide-1 receptor agonist alters the provoked headache in IIH by reducing brain pressure. Further, we aim to investigate the impact of exercise, straining and sleep on brain pressure and blood flow.
Who can participate?
Patients aged 18 to 60 years old who are diagnosed with IIH
What does the study involve?
Patients will have a brain pressure monitor inserted where possible. We will explore in detail the role of CGRP by administering this to patients and assessing if it will cause typical IIH headaches. We will be monitoring brain pressure changes and brain blood flow during these IIH headaches. Patients will also receive a glucagon-like peptide-1 receptor agonist to lower the brain pressure after a headache.
What are the possible benefits and risks of participating?
There are potential benefits to involvement including enhanced observation during the trial and opportunities to improve understanding of the condition. The brain pressure monitor allows measurement without further invasive procedures which most IIH patients may require frequently to measure brain pressure. There is a beneficial effect on brain pressure for those who get a headache provocation and receive the active drug. Also, glucagon-like peptide-1 receptor agonists are known to facilitate weight loss. Furthermore, if a participant suffers a spontaneous headache and attends the research visit, they will benefit from acute in-hospital symptom management.
The major risks in this study relate to the implantable telemetric pressure monitor sensor and the surgical procedure to fit it and to the study medication. There is a small risk from using anesthesia as well as small risks from the procedure of bleeding near the brain, infection or seizures after the procedure. There is a small risk that the device could fail which requires another surgery to remove the device. There are risks of flushing, warm sensation, palpitation and nausea due to the medications. There are rare reports of pancreatitis and low blood pressure associated with the medications.
Where is the study run from?
University of Birmingham (UK)
When is the study starting and how long is it expected to run for?
August 2021 to July 2025
Who is funding the study?
1. Association of British Neurologists (UK)
2. Guarantors of Brain (UK)
Who is the main contact?
Dr Andreas Yiangou
a.yiangou@bham.ac.uk
Contact information
Scientific
Institute of Metabolism and Systems Research
IBR Tower
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
 ORCID ID |
0000-0001-8905-5734 |
|---|---|
| Phone | +44 (0)1213712000 |
| a.yiangou@bham.ac.uk |
Principal Investigator
Institute of Metabolism and Systems Research
IBR Tower
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
| ORCID ID |
0000-0003-2777-5132 |
|---|---|
| Phone | +44 (0)1213712000 |
| a.b.sinclair@bham.ac.uk |
Study information
| Study design | Prospective randomized placebo-controlled two-way crossover cohort study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Mechanisms driving headache in idiopathic intracranial hypertension, a human physiology study |
| Study acronym | IIH Provoke |
| Study objectives | 1. Elevations of intracranial pressure (ICP) in Idiopathic intracranial hypertension (IIH) drive headache signalling through the release of calcitonin gene-related peptide (CGRP). 2. Reducing ICP by targeting the glucagon-like peptide 1 receptor (GLP-1R) signalling pathways alters the headache and cerebrovascular dynamics during a provoked IIH headache. |
| Ethics approval(s) | Approved 27/06/2022, North East - Newcastle & North Tyneside 1 Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ, UK; +44 (0)20 7104 8255; newcastlenorthtyneside1.rec@hra.nhs.uk), ref: 22/NE/0081 |
| Health condition(s) or problem(s) studied | Idiopathic intracranial hypertension |
| Intervention | IIH Provoke is a prospective, randomised, double-blind, placebo-controlled two-way crossover physiology study. Up to 24 patients with idiopathic intracranial hypertension (IIH) will undergo headache provocation study days. Where possible an intracranial pressure (ICP) monitor will be inserted (unless one previously inserted for clinical reasons). Participants will be identified at University Hospitals Birmingham NHS Foundation Trust (UHB) within our IIH clinical network during routine clinical appointments by the direct clinical care team. Potential participants will be approached by the direct clinical care team about interest in participating in research after brief eligibility criteria check performed in the clinic or from clinical records and a Patient information sheet will be given or sent out. Patients will have at least 7 days to consider the study and will be invited for a screening and enrolment visit. Consent will be taken at the beginning of the screening visit. A targeted medical and headache history will be taken along with targeted medical, neuro-ophthalmological assessments. Completion of questionnaires will take place and a headache diary will be dispensed to be completed for the duration of the study. Participants eligible will be enrolled and allocated a study participant identification number (SPIN). Randomisation allocation will take place using this number from the prepopulated computer-generated randomisation list. If a participant will have an ICP monitor inserted, they will attend for pre-surgical (pre-op) assessment and a surgical visit for the ICP monitor insertion (day-case). For the main study each participant will be attending for at least 2 research visits. On one visit they will receive a provocation agent: intravenous calcitonin gene-related peptide (CGRP, 30mcg) and on the other visit, a placebo (normal saline). This will be in a random order (cross-over design with randomisation as above). Targeted medical history, headache scores, quality of life questionnaires, ICP and cerebrovascular recordings (where applicable) will be undertaken. Headache diary will be reviewed and new one dispensed if needed. We will be assessing the effect of the provocation agent on headache, ICP and brain blood flow (where applicable). If a headache provocation takes place, participants will then receive an ICP lowering agent: Exenatide (20mcg) or a placebo (normal saline) on that day. This will be in random order (cross-over design with randomisation as above). They will attend for one additional visit to receive provocation agent and the alternate ICP lowering agent (assessments as above). We will be assessing the effect of the ICP lowering agent Exenatide on headache, ICP and brain blood flow (where applicable). In optional substudies we will be evaluating the effect of straining, exercise, sleep (assessments as above) and investigate for headache biomarkers. |
| Intervention type | Other |
| Primary outcome measure | The following measures were assessed after a single visit: 1. Incidence of provoked headache akin to the participant's typical IIH headache measured using a Headache assessment tool 2. Change in intracranial pressure (ICP) during a headache attack determined using physiological measurement 3. Headache physiological response over the 24 hours post-dose measured using a Headache assessment tool |
| Secondary outcome measures | The following measures were assessed after a single visit: 1. Change in headache features measured using a Headache assessment tool and diary 2. Dynamic changes in cerebrovascular physiology and headache biomarkers determined using physiological measurement |
| Overall study start date | 01/08/2021 |
| Completion date | 31/07/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 60 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 24; UK Sample Size: 24 |
| Key inclusion criteria | 1. Aged between 18 and 60 years old 2. Previous diagnosis of idiopathic intracranial hypertension (IIH) 3. Able to give informed consent |
| Key exclusion criteria | 1. Aged less than 18 or older than 60 years old 2. Optic nerve elevation exclusively due to pseudopapilloedema 3. Previous migraine history prior to the diagnosis of IIH (or non-IIH headache) > 1 day per month 4. Pregnant or trying to conceive 5. Significant co-morbidity; such that in the opinion of the investigator it would not be in the participant’s best interest to participate in the trial 6. Known cardiovascular or cerebrovascular disease 7. Medication overuse 8. Inability to comply with study schedule or follow-up 9. Currently using Glucagon-like peptide-1 receptor (GLP-1R) agonist or Dipeptidyl-peptidase 4 (DPP-4) inhibitor 10. Contra-indications to undergoing a surgical procedure |
| Date of first enrolment | 13/02/2023 |
| Date of final enrolment | 31/05/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
United Kingdom
Sponsor information
University/education
C/o: Birgit Whitman
Head Research Governance & Integrity
Rm 106, B Block Aston
Webb Building
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| Phone | +44 (0)7814 650 003 |
|---|---|
| researchgovernance@contacts.bham.ac.uk |
Funders
Funder type
Charity
No information available
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/08/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
01/03/2024: The contact confirmed the record is up to date.
09/02/2023: The recruitment end date was changed from 06/02/2023 to 13/02/2023.
16/01/2023: The recruitment start date was changed from 16/01/2023 to 06/02/2023.
13/12/2022: The recruitment start date was changed from 19/12/2022 to 16/01/2023.
07/11/2022: The recruitment start date was changed from 01/11/2022 to 19/12/2022.
27/09/2022: Trial's existence confirmed by the NIHR.
