Safety and Effectiveness of 11b-Hydroxysteroid Dehydrogenase Type 1 Inhibitor (AZD4017) to Treat Idiopathic Intracranial Hypertension.
Condition: Idiopathic Intracranial Hypertension
MeSH terms: Intracranial Hypertension; Pseudotumor Cerebri; Hypertension
Study type: Interventional
Phase: Phase 2

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.
    


Intervention name(s): AZD4017; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Matched placebo (matched to AZD4017 arm)
Other intervention name(s): 11b-Hydroxysteroid dehydrogenase type 1 inhibitor
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Pseudotumor Cerebri; Benign Intracranial Hypertension; Headaches; Tinnitus; Papilledema; Blindness; Optic Disk; Intracranial Hypertension; Clinical Trial, Phase 2; 11beta-Hydroxysteroid Dehydrogenase Type 1; Obesity