IIH Provoke

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

Patients aged 18 to 60 years old who are or have been diagnosed with IIH. 

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.

This is a prospective randomized placebo-controlled two-way crossover cohort study. 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.

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.

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).
Following the initial contact by the clinical team, potential participants 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.
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.
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 provocation agent on headache, ICP and brain blood flow (where applicable).

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.