The AXIS Study: the Efficacy of Acetazolamide for the Treatment of Cystoid Fluid Collections in Retinoschisis
Status:
Recruiting
Trial end date:
2025-03-20
Target enrollment:
Participant gender:
Summary
X-linked retinoschisis (XLRS) is a rare hereditary eye disease that causes irreversible
vision loss in boys and young men. This disease occurs in 1 in 10,000-30,000. This inherited
condition is caused by pathogenic variants in a single gene, namely the Retinoschisin 1
(RS1). This gene encodes the retinoschisin protein. Pathological variants of retinoschisin
lead to loss of retinal integrity, resulting in the characteristic cystoid fluid collections
(CFC). From a young age, XLRS patients experience a gradual deterioration of vision. In
middle-aged patients however, XLRS may be associated with macular atrophy because of the
confluence of the cystoid lesions. No permanent treatment is yet available for XLRS patients.
Currently, two different phase I/II studies are investigating the safety and effectivity of
subretinal gene therapy. To create optimal retinal condition before gene therapy, CFC, a
hallmark of XLRS, should not be present. Topical and oral carbonic anhydrase II inhibitors
are used to combat CME. This drug is still off-label prescribed for various hereditary
retinal dystrophies. Consequently, there is no treatment regimen for prescribing
acetazolamide to XLRS patients. A thorough understanding of the safety and efficacy of
acetazolamide in reducing the central foveal thickness in XLRS patients is required before
applying future gene therapy.
The proposed study is a investigator-initiated, single-center, prospective, experimental
study consisting of seven visits at 2, 4, 12, 16, 20 and 32 weeks after the baseline
evaluation visit. During each visit, participants will perform several ophthalmological
measurements. In this study, participants with XLRS will be randomized into either a
treatment or control group. The null-hypothesis of this study is that acetazolamide
effectively reduces the central foveal thickness in patients with XLRS and significantly
improves their visual function. The alternative hypothesis is that acetazolamide reduces not
effectively the central foveal thickness in patients with XLRS and has no significant impact
on their visual function. Treatment success will be based not only on anatomical improvement,
but also on functional endpoints, which are most important from a patient's perspective. The
study will last 32 weeks per participant. Each participant will come physically for seven
visits. The whole study will last for max. 24 months. The examinations and number of visits
are reduced to a minimum. In contrast to clinical care, the participants receive examinations
that consist of a more extensive measurement of visual acuity, microperimetry and a
questionnaire. These extra examinations are required to evaluate the functional
vision-related endpoints of the study.
Phase:
Phase 2
Details
Lead Sponsor:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)