Conditions: Idiopathic Intracranial Hypertension
Keywords: Pseudotumor Cerebri Benign Intracranial Hypertension Headaches Tinnitus Papilledema Blindness Optic Disk Intracranial Hypertension Clinical Trial, Phase 2 11beta-Hydroxysteroid Dehydrogenase Type 1 Obesity
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 31
Healthy volunteers: no

Brief summary:
Assessing the safety and effectiveness of a 11-βhydroxysteroid dehydrogenase type 1 inhibitor (AZD4017), in a placebo controlled trial, in acute idiopathic intracranial hypertension (IIH) IIH is a condition of young, overweight women with characteristic raised intracranial pressure (pressure around the brain) leading to papilloedema (swelling of the nerve supplying the eye), visual loss and headaches. Medical literature (Cochrane review) demonstrates there is little evidence for the treatments used for IIH. Weight control appears the most effective method of improving symptoms but weight loss is difficult to maintain. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme which regulates local steroid levels and our previous research suggests it may influence the production of brain fluid(cerebrospinal fluid or CSF). 11β-HSD1 levels fall with weight loss and this is associated with with decreased intracranial pressure.

Our primary outcome is to determine whether AZD4017, an inhibitor of 11β-HSD1, will reduce the pressure in the brain and as a consequence improve IIH. Patients are eligible to enter the study if they are between 18-55 years old with acute (\<6 months) IIH, signs of active disease (papilloedema and raised CSF pressure (\>25 cmH20)), no other major illnesses and have no plans for pregnancy during the study period.

This is an MRC funded single centre, phase II, double-blinded, randomised control drug trial. It will be conducted at the University Hospital Birmingham and the University of Birmingham will act as Sponsor. Eligible participants will be randomly assigned to AZD4017 or a placebo ('dummy' with no active drug) for 3 months with a follow up a month later. Investigations during the study will include bloods, urine samples, pregnancy tests, lumbar punctures, DXA scans and small fat/skin biopsies. Participants will benefit from increased monitoring and a potential improvement in their condition.

We hypothesise that specific inhibition of 11β-HSD1 will decrease intracranial pressure and consequently treat patients with IIH, thus opening a new and entirely novel therapeutic avenue.

Detailed description:

Arms:
arm 1: Matched placebo tablet B.D for 12 weeks arm 2: AZD4017 400mg tablet B.D. for 12 weeks

Interventions: intervention 1: AZD4017 intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: Matched placebo (matched to AZD4017 arm)

Protocol document: