The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) (as of year 2022) is the largest randomized controlled trial in the field of IIH.
A randomized controlled trial means that participants in the trial will be divided in groups, usually two, one that will receive the treatment studied and the other to receive the “placebo”, which is an inactive pill or a sham procedure. Participants will be randomly selected by chance into one of the groups. A randomized controlled trial is considered the gold standard in medical research because it limits bias (prejudice from the patient or the physician for or against a treatment). Additionally, the IIHTT was double-blind, which means that neither the participant nor the physician knew if the participant was taking the active drug or the placebo.
The IIHTT enrolled participants from 2010 to 2012. It studied 165 IIH patients with mild visual field loss and followed them for 6 months. The study drug was acetazolamide (or Diamox) given at a dose of 1mg to 4mg daily. 86 participants received acetazolamide and 79 the placebo. All participants were also recommended to follow a low-salt weight-reduction diet.
The IIHTT showed that, in patients with mild visual field loss, acetazolamide was in general well tolerated and improved modestly the visual field, mostly in patients with severe papilledema. Acetazolamide also generally improved the quality of life despite its side effects but did not improve headaches (as measured by the HIT-6 test) compared to placebo.
If you want more detailed information about the IIHTT we recommend the following articles:
The idiopathic intracranial hypertension treatment trial: a review of the outcomes, by SV Smith and DJ Friedman. This is a nice and easy-to-read review summarizing the 14 articles that reported the outcomes of the IIHTT. The abstract is available for free: doi.org/10.1111/head.13144
The Idiopathic Intracranial Hypertension Treatment Trial: Design Considerations and Methods by Friedman et al. If you want to understand why and how the IIHTT was conceived. The entire article is available for free: doi.org/10.1097/WNO.0000000000000114
Effect of Acetazolamide on Visual Function in Patients With Idiopathic Intracranial Hypertension and Mild Visual Loss. The Idiopathic Intracranial Hypertension Treatment Trial, by M Wall et al. for the NORDIC study group. This is a scholarly article reporting of the primary outcome of the IIHTT. The conclusion of the investigators was: “In patients with IIH and mild visual loss, the use of acetazolamide with a low-sodium weight-reduction diet compared with diet alone resulted in modest improvement in visual field function. The clinical importance of this improvement remains to be determined.” The abstract is available for free at: doi.org/10.1001/jama.2014.3312
An earlier prospective randomized trial of acetazolamide versus placebo was performed in 6 neurology centers in the UK (Ball et al, 2011). It enrolled 50 patients and followed them every 3 months up to one year. 25 patients were randomized to acetazolamide and 25 to placebo. The investigators did not find a treatment effect, probably due to the small number of patients enrolled and the poor tolerance of acetazolamide in the treatment group (48% of patients stopped taking the medication). The investigators suggested performing a larger trial. The summary of the study is available for free at: doi.org/10.1007/s00415-010-5861-4