RetinoschisisPhase 2AXISNCT06114537
The AXIS Study: the Efficacy of Acetazolamide for the Treatment of Cystoid Fluid Collections in Retinoschisis
A Phase 2 study testing Acetazolamide in people with Retinoschisis, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial 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). Read more about this study
- Who is it for?
- Ages 12 years and older, men only
- Conditions the study is for
- Retinoschisis
- What is being tested?
- Acetazolamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteNetherlands
- Study dates
- 20 Jan 2023to 13 Sep 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with XLRS with cystoid fluid collections involving the fovea confirmed on SD- OCT
- are willing to undergo ophthalmic examinations at seven separate occasions;
- have no visual dysfunction that is also significantly associated with other ocular diseases besides XLRS (e.g., glaucoma, perforating trauma);
- have no known (non-)ocular disease/disorder which may influence the results of the measurements.
Who cannot join
- Severe hepatic impairment
- Severe renal insufficiency
- Sodium and Potassium Depletion
- Addison's disease
- Hyperchloremic Acidosis
- Cor pulmonale
Show all 9Show fewer
- Chronic non-congestive angle-closure glaucoma
- Usage of acetazolamide
- Known allergy or intolerance for ocular anesthetic eye drops oxybuprocaine 0.4% or mydriatics tropicamide 0.5% and/or phenylephrine 5%;
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Amsterdam University Medical Centers
Amsterdam, North Holland, 1105AZ
About this study
Official title: Randomized Clinical Trial to Evaluate the Efficacy of Acetazolamide for the Treatment of Cystoid Fluid Collections in Retinoschisis: The AXIS Trial
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 CFC. 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.
- Conditions
- Retinoschisis
- Being tested
- Acetazolamide
- Keywords
- X-Linked Retinoschisis, X-Linked Juvenile Retinoschisis
- Medical subject headings
- Retinoschisis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetazolamideDrug
Also called Diamox
The used intervention in this study is acetazolamide, which belongs to a class of drugs known as carbonic anhydrase inhibitors and has been used with other medications to treat high ocular pressure due to certain types of glaucoma
Patients in the treatment group will receive 250 milligrams of oral acetazolamide twice daily for 16 weeks.
Patients randomized to the treatment group will switch to 125 milligrams of oral acetazolamide twice daily for another four weeks when the central foveal thickness (CFT) on OCT is reduced by ≥25% at the evaluation visit at 16 weeks after the baseline visit. These patients will continue with this dose till the end of the study when the CFT on OCT is stable or further reduced. If the CFT on OCT has increased, they switch back to 250 milligrams of oral acetazolamide twice daily for another 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Experimental | Patients in the treatment group receives twice daily a 250mg tablet acetazolamide for 16 weeks. At week 16, depending on the results, the treated group will stop the treatment or continue with a lower dose twice daily a 125mg tablet acetazolamide for 4 weeks. At week 20, depending on the results, the initial treated group will continue with twice daily a 125mg tablet or go back to twice daily a 250mg tablet acetazolamide till week 32. Receives: Drug: Acetazolamide |
| Control Group | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Macular structure as assessed by spectral domain optical coherence tomography
Change in Central subfield thickness on spectral domain optical coherence tomography (SD-OCT).
Measured: Change from baseline to Week 32
Secondary outcomes (5)
Visual acuity as assessed by low-luminance visual acuity
Change in low luminance visual acuity (LLVA)
Measured: Change from baseline to Week 32
Visual function as assessed by microperimetry
Change in microperimetry.
Measured: Change from baseline to Week 32
Subject-reported visual function as assessed by the Michigan Retinal Degeneration Questionnaire (MRDQ).
Change in the functional (dis)ability score, theta score (θ), in the measured trait or domain. Θ is centred at the mean trait level of the patient population of the developers with a variance of 1, and extreme Θ-values -3 and + 3 indicate lowest and highest visual disability respectively of each patients.
Measured: Change from baseline to Week 32
Absence of cystoid fluid collections on OCT scan
Absence of cystoid fluid collections on OCT scan
Measured: At evaluation visits during study (assessed up to 32 weeks)
Visual acuity as assessed by best-corrected visual acuity
Change in in best-corrected visual acuity (BCVA).
Measured: Change from baseline to Week 32
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2023
- Study start20 Jan 2023
- Primary completion13 Sep 2024
- Study completion13 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RetinoschisisStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized into the treatment group or the control group.
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Camiel J. F. Boon, Amsterdam UMC, location AMC
- Investigators
- Camiel JF Boon, Prof. dr., Principal investigator, Amsterdam UMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06114537
- Sponsor's protocol ID
- NL80249.018.22
- Acronym
- AXIS
- Status last verified
- May 2025
- First submitted
- 24 Oct 2023
- Last updated
- 31 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Clinical Trial to Evaluate the Efficacy of Acetazolamide for the Treatment of Cystoid Fluid Collections in Retinoschisis: The AXIS Trial
- ClinicalTrials.gov ID
- NCT06114537
- Acronym / sponsor ID
- AXIS / NL80249.018.22
- Conditions
- Retinoschisis
- Keywords
- X-Linked Retinoschisis, X-Linked Juvenile Retinoschisis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- 20 Jan 2023 (actual)
- Primary completion
- 13 Sep 2024 (actual)
- Study completion
- 13 Sep 2024 (actual)
- First posted
- 2 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 CFC. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients will be randomized into the treatment group or the control group.
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Experimental | Drug: AcetazolamidePatients in the treatment group receives twice daily a 250mg tablet acetazolamide for 16 weeks. At week 16, depending on the results, the treated group will stop the treatment or continue with a lower dose twice daily a 125mg tablet acetazolamide for 4 weeks. At week 20, depending on the results, the initial treated group will continue with twice daily a 125mg tablet or go back to twice daily a 250mg tablet acetazolamide till week 32. |
| Control Group | No intervention | – |
Who may qualify
- Ages
- 12 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with XLRS with cystoid fluid collections involving the fovea confirmed on SD- OCT
- are willing to undergo ophthalmic examinations at seven separate occasions;
- have no visual dysfunction that is also significantly associated with other ocular diseases besides XLRS (e.g., glaucoma, perforating trauma);
- have no known (non-)ocular disease/disorder which may influence the results of the measurements.
Key exclusion criteria (9 listed)
- Severe hepatic impairment
- Severe renal insufficiency
- Sodium and Potassium Depletion
- Addison's disease
- Hyperchloremic Acidosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcetazolamideAlso: DiamoxThe used intervention in this study is acetazolamide, which belongs to a class of drugs known as carbonic anhydrase inhibitors and has been used with other medications to treat high ocular pressure due to certain types of glaucoma Patients in the treatment group will receive 250 milligrams of oral acetazolamide twice daily for 16 weeks. Patients randomized to the treatment group will switch to 125 milligrams of oral acetazolamide twice daily for another four weeks when the central foveal thickness (CFT) on OCT is reduced by ≥25% at the evaluation visit at 16 weeks after the baseline visit. These patients will continue with this dose till the end of the study when the CFT on OCT is stable or further reduced. If the CFT on OCT has increased, they switch back to 250 milligrams of oral acetazolamide twice daily for another 12 weeks. | Drug | Treatment group |
Primary outcome
Macular structure as assessed by spectral domain optical coherence tomography
Time frame: Change from baseline to Week 32
Change in Central subfield thickness on spectral domain optical coherence tomography (SD-OCT).
5 secondary outcomes
Visual acuity as assessed by low-luminance visual acuity
Time frame: Change from baseline to Week 32
Visual function as assessed by microperimetry
Time frame: Change from baseline to Week 32
Subject-reported visual function as assessed by the Michigan Retinal Degeneration Questionnaire (MRDQ).
Time frame: Change from baseline to Week 32
Absence of cystoid fluid collections on OCT scan
Time frame: At evaluation visits during study (assessed up to 32 weeks)
Visual acuity as assessed by best-corrected visual acuity
Time frame: Change from baseline to Week 32
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Camiel JF Boon, Prof. dr. principal investigator
Amsterdam UMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acetazolamide in people with Retinoschisis, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Macular structure as assessed by spectral domain optical coherence tomography (time frame: Change from baseline to Week 32). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2025.