IIH Pressure - a new treatment for raised brain pressure in Idiopathic Intracranial Hypertension

INTERVENTION: The main part of the trial has two arms, active treatment and placebo. The second part of the trial is single arm and open to all participants on the main trial. First part of the study: The randomisation process for the main trial is by computer generated list. The active treatment arm receives a single bolus of the study drug, exenatide at baseline. The dose is 20mcg Exenatide (Byetta) via subcutaneous injection. Following the baseline day all active arm participants receive 10mcg Exenatide (Byetta) via subcutaneous injection twice daily and self administer. The duration of treatment is 12 weeks. Follow‐up takes place at two weeks and 12 weeks. The placebo arm receives a single bolus of Normal Saline Placebo at baseline. The dose includes 1 mL via subcutaneous injection. Following the baseline day all placebo arm participants receive 0.5 mL Normal Saline via subcutaneous injection twice daily and will self administer. The duration of treatment will be 12 weeks. Follow‐up is done at two weeks and 12 weeks. Follow up is done at two and 12 weeks where participants undergo Intracranial pressure (ICP) recording, IOP, blood sampling, OCT, headache scores and cognitive testing. Additionally, at 12 weeks participants also undergo clinical measurements, quality of life questionnaires, and DEXA scan. Second part of the study: This pat of the study is a single arm sequential, open label design. All participants receive all medications in random order. The duration of treatment is two weeks, week one is a titration week where necessary. There will be a minimum one week washout between rounds. Follow‐up is by visit at two weeks. The medications for this part of the study are: Acetazolomide: Patients take 500mg BD PO immediate release for seven days, followed by 1g BD for seven days. Spironolactone: Participants take 100mg OD PO for seven days, followed by 200mg OD for seven days. Amiloride: Participants take 10mg OD PO for 14 days. Furosemide: Patients take 40mg OD CONDITION: Specialty: Neurological disorders, Primary sub‐specialty: Other; UKCRC code/ Disease: Neurological/ Other disorders of the nervous system ; Nervous System Diseases ; Neurological disorders PRIMARY OUTCOME: 1. Change in Intracranial pressure (ICP) measured by telemetric ICP catheter between baseline and 24 hours post drug administration; 2. Change in ICP measured by telemetric ICP catheter between baseline and end of trial visit; 3. Change in ICP measured by telemetric ICP catheter between baseline and two and a half hours post administration SECONDARY OUTCOME: 1. Biological effects of exenatide is measured using blood tests at 24 hours, two and 12 weeks; 2. Headaches are measured using severity scores at 24 hrs, two and 12 weeks; 3. Quality of life are measured using SF‐36 at baseline and 12 weeks; 4. CSF exenatide levels are measured by assay at two and a half, six and 11 hours INCLUSION CRITERIA: 1. Female 2. Aged 18‐60 years old 3. Diagnosed with IIH by the modified Dandy criteria 4. Active disease (papilloedema Frisen grade greater than 1) 5. Significantly raised ICP (greater than 25cm CSF) 6. No evidence of venous sinus thrombosis (documented normal MR Venogram of CT Venogram) 6. Able to provide informed consent