Safety and Effectiveness of 11b-Hydroxysteroid Dehydrogenase Type 1 Inhibitor (AZD4017) to Treat Idiopathic Intracranial Hypertension. (IIH:DT)
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|ClinicalTrials.gov Identifier: NCT02017444|
Recruitment Status : Completed
First Posted : December 20, 2013
Results First Posted : October 27, 2021
Last Update Posted : October 27, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Idiopathic Intracranial Hypertension||Drug: AZD4017 Other: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||31 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||Lowering Intracranial Pressure in Idiopathic Intracranial Hypertension: Assessing the Therapeutic Efficacy and Safety of an 11β-hydroxysteroid Dehydrogenase Type 1 Inhibitor (AZD4017). Phase II Study.|
|Actual Study Start Date :||April 25, 2014|
|Actual Primary Completion Date :||December 19, 2016|
|Actual Study Completion Date :||December 19, 2016|
Placebo Comparator: Placebo
Matched placebo tablet B.D for 12 weeks
Matched placebo (matched to AZD4017 arm)
Active Comparator: AZD4017 (11b-HSD1 inhibitor)
AZD4017 400mg tablet B.D. for 12 weeks
Other Name: 11b-Hydroxysteroid dehydrogenase type 1 inhibitor
- Intracranial Pressure [ Time Frame: 12 weeks ]ICP measured by lumbar puncture in cmCSF as the change from week 0 and week 12 of treatment, measured at baseline and week 12
- Tinnitus [ Time Frame: 12 weeks ]The temporal change in IIH symptoms (presence or absence of tinnitus), measured at baseline and week 12
- Anthropometric Measurements (BMI) [ Time Frame: 12 weeks ]The temporal change in Body Mass Index (in kg/m^2) over 12 weeks of treatment, measured at baseline and week 12
- Visual Loss [ Time Frame: 12 weeks ]The temporal change in IIH symptoms (presence or absence of visual loss, measured at baseline and week 12
- Diplopia [ Time Frame: 12 weeks ]The temporal change in IIH symptoms (presence or absence of diplopia, measured at baseline and week 12
- Visual Obscuration [ Time Frame: 12 weeks ]The temporal change in IIH symptoms (presence or absence of visual obscuration, measured at baseline and week 12
- Headache [ Time Frame: 12 weeks ]The temporal change in IIH symptoms (presence or absence of headache, measured at baseline and week 12
- Visual Acuity [ Time Frame: 12 weeks ]The temporal change in IIH visual function in both eyes (measured by LogMAR (log of the minimum angle of resolution) chart to assess visual acuity, between the baseline to week 12, measured at baseline and week 12
- Papilloedema [ Time Frame: 12 weeks ]
The temporal change in papilloedema (evaluated at the end of trial follow up using stereoscopic fundus photographs by masked neuro-ophthalmologists to grade the images according to Frisen classification) measured at baseline and week 12. There are 6 grades, 0-5, 5 being the worst.
The modified Frisén scale for grading papilledema using fundus photography is as follows:
Grade 1 - C-Shaped halo with a temporal gap
Grade 2 - The halo becomes circumferential
Grade 3 - Loss of major vessels as they leave the disc
Grade 4 - Loss of major vessels on the disc
Grade 5 - Criteria of Grade IV + partial or total obscuration of all vessels on the disc
For further details see e.g. Scott, C.J., et al., Diagnosis and grading of papilledema in patients with raised intracranial pressure using optical coherence tomography vs clinical expert assessment using a clinical staging scale. Arch. Ophthalmol, 2010. 128(6): p. 705-711.
- Headache-associated Disability [ Time Frame: 12 weeks ]The change in headache associated disability through the headache impact test-6 score (HIT 6), measured at baseline and week 12. This is scored 11-66 with higher scores indicating worse headache.
- Adverse Events [ Time Frame: 16 weeks ]The safety and tolerability profile of AZD4017 in female patients with IIH through adverse event reporting and safety bloods.
- Serious Adverse Events [ Time Frame: 16 weeks ]The safety and tolerability profile of AZD4017 in female patients with IIH through adverse event reporting and safety bloods.
- OCT Total Average Retinal Nerve Fibre Layer Thickness (μm) [ Time Frame: 12 weeks ]The temporal change in OCT Total average retinal nerve fibre layer thickness (μm), measured at baseline and week 12
- Visual Field Mean Deviation [ Time Frame: 12 weeks ]The temporal change in IIH visual function in both eyes using automated perimetry (Humphrey 24-2 central threshold) to measure the visual field mean deviation between the baseline to week 12
- Log Contrast Sensitivity [ Time Frame: 12 weeks ]The temporal change in IIH visual function in both eyes using a Pelli-Robson chart to evaluate log contrast sensitivity between the baseline to week 12
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02017444
|University Hospital Birmingham (Queen Elizabeth Hospital)|
|Birmingham, West Midlands, United Kingdom, B15 2TH|
|Principal Investigator:||Alexandra Sinclair, MbChb PhD||University of Birmingham|