Assessing the Efficacy and Safety of an 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor (AZD4017) in the Idiopathic Intracranial Hypertension Drug Trial, IIH:DT: Clinical Methods and Design for a Phase II Randomized Controlled Trial

Keira Annie Markey, Ryan Ottridge, James L Mitchell, Caroline Rick, Rebecca Woolley, Natalie Ives, Peter Nightingale, Alexandra J Sinclair, Keira Annie Markey, Ryan Ottridge, James L Mitchell, Caroline Rick, Rebecca Woolley, Natalie Ives, Peter Nightingale, Alexandra J Sinclair

Abstract

Background: Idiopathic intracranial hypertension (IIH) is a condition with few effective management options. So far, there have been no randomized controlled trials evaluating new treatments in IIH.

Objectives: The purpose of this paper is to outline the trial design for the Idiopathic Intracranial Hypertension Drug Trial (IIH:DT), assessing an innovative medical treatment in IIH and the rationale for the chosen trial methodology.

Methods: IIH:DT is a phase II double-blind randomized placebo-controlled trial recruiting 30 female participants with active IIH (intracranial pressure >25cm H2 O and papilledema). Participants are randomized in a 1:1 ratio to 12 weeks of either AZD4017, an 11β-hydroxysteroid dehydrogenase type 1 inhibitor, or a matching placebo. They receive either 400 mg of AZD4017 or placebo twice daily. Participants are followed up at Weeks 1, 2, 3, 4, 6, 8, 10, 12, and 16 postrandomization. The primary outcome is to examine the effect of AZD4017 on intracranial pressure, measured by lumbar puncture, over 12 weeks. Secondary outcome measures include IIH symptoms, visual function, papilledema, headache measures, safety, and tolerability. Cerebrospinal fluid, serum, plasma, urine, and adipose tissue are also taken for exploratory outcomes.

Results: All participants were recruited between April 2014 and August 2016.

Conclusions: IIH:DT is the first phase II double-blind randomized placebo-controlled trial assessing the efficacy and safety of the novel pharmacological intervention, AZD4017, for the treatment of IIH.

Trial registration: Clinicaltrials.gov NCT02017444; https://ichgcp.net/clinical-trials-registry/NCT02017444 (Archived by WebCite at http://www.webcitation.org/6tVHesN6s).

Keywords: 11beta-HSD1; clinical protocol; clinical trials, Phase II; idiopathic intracranial hypertension; randomised controlled trial.

Conflict of interest statement

Conflicts of Interest: AstraZeneca provided this study (through their chosen contract manufacturing organization, Almac) with the trial medication, AZD4017 and placebo. However, they were not involved in any part of the design or implementation of the study, apart from aspects of safety, and have no influence over its course.

©Keira Annie Markey, Ryan Ottridge, James L Mitchell, Caroline Rick, Rebecca Woolley, Natalie Ives, Peter Nightingale, Alexandra J Sinclair. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 18.09.2017.

Figures

Figure 1
Figure 1
IIH:DT trial design.
Figure 2
Figure 2
Overview of the screening visit.

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