Gyrate AtrophyGYROSNCT05312736
Gyrate Atrophy Ocular and Systemic Study
An observational study of Gyrate Atrophy and Gyrata of Choroid and Retina; Atrophy, run by Jaeb Center for Health Research at 11 sites in 8 countries.
Trial summary
The Gyrate Atrophy Ocular and Systemic Study characterizes the natural history of ornithine levels and retinal degeneration (RD) associated with disease-causing OAT variants in the presence of standard care dietary treatment regimens over 4 years. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Gyrate Atrophy, Gyrata of Choroid and Retina; Atrophy, Ornithine-δ-aminotransferase
- How many people
- 46 participants
- Where
- 11 sitesin 8 countries
- Study dates
- 21 Nov 2023to 31 Dec 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: The target population for GYROS will be patients with gyrate atrophy associated with disease-causing variants in the OAT gene.
Who may be able to join
- Participants must meet all the following inclusion criteria at the Screening Visit in order to be eligible to enroll into the genetic screening phase.
- Willing to participate in the study and able to communicate consent during the consent process.
- Willing and able to complete all study visit assessments at each visit over the forty-eight (48) month study period. Age ≥ 12 years.
- Must meet one (1) of the Genetic Screening Criteria below:
- At least 2 disease-causing variants in the OAT gene which are homozygous or heterozygous in trans, based on a report from a clinically certified lab, or a report from a research lab that has been pre-approved by the study Genetics Committee.
- At least 2 disease-causing variants in the OAT gene with unknown phase, based on a report from a clinically certified lab, or a report from a research lab that has been pre-approved by the study Genetics Committee, AND must meet both of the following phenotype criteria: .Classic fundus appearance of gyrate atrophy (based on investigator discretion) AND Elevated ornithine levels >300 μmol/L (documented on any prior lab report).
- Note: if a participant has a variant(s) of unknown significance, they will still qualify if they meet the Genetic Screening Criteria above. Ocular Inclusion Criteria Participant must meet the following criteria at the Screening Visit to enroll into the genetic screening phase.
- Both eyes must have a clinical diagnosis of retinal dystrophy. Both eyes must permit good quality photographic imaging (e.g., but not limited to, clear ocular media, adequate pupil dilation, stable fixation).
Who cannot join
- Participants must not meet any of the following exclusion criteria at the Screening Visit in order to be eligible to enroll into the genetic screening phase.
- Single pathogenic or likely pathogenic genetic variants known to be associated with autosomal dominant retinitis pigmentosa/retinal dystrophy (AD, heterozygous), X-374 linked retinitis pigmentosa/retinal dystrophy (XL, hemizygous), or mitochondrial inheritance.
- Expected to enter experimental treatment trial at any time during this study. History of more than 1 year of cumulative treatment, at any time, with an agent associated with pigmentary retinopathy, including hydroxychloroquine, chloroquine, thioridazine, and deferoxamine. Note: Since this is a Natural History Study collecting data on the progression of Gyrate Atrophy, pregnant women will not be specifically excluded from participation.
- Ocular Exclusion Criteria:
- If either eye has any of the following ocular exclusion criteria at the Screening Visit, then the participant is not eligible to enroll into the genetic screening phase.
- Current vitreous hemorrhage.
Show all 18Show fewer
- Current or any history of tractional or rhegmatogenous retinal detachment.
- Current or any history of (for example, but not limited to prior to cataract or refractive surgery) spherical equivalent of the refractive error worse than -8 Diopters of myopia. • • • History of intraocular surgery (for example, but not limited to cataract surgery, vitrectomy, penetrating keratoplasty, or LASIK) within the last 3 months.
- Current or any history of confirmed diagnosis of glaucoma (for example, but not limited to glaucomatous VF changes or nerve changes, or history of glaucoma filtering surgery). e. Current or any history of retinal vascular occlusion or proliferative diabetic retinopathy.
- History or current evidence of ocular disease that, in the opinion of the investigator, may confound assessment of visual function.
- The following medications and treatments are prohibited as they can affect progression of retinal pigmentosa. The participant must not have received or planning to receive the following treatments.
- Any use of ocular stem cell or gene therapy.
- Any treatment with ocriplasmin.
- Treatment with Ozurdex (dexamethasone), Iluvien or Yutiq (fluocinolone 404 acetonide) intravitreal implant.
- The following medications and treatments are excluded within the specified timeframe:
- Treatment with an ophthalmic oligonucleotide within the last 9 months (last treatment date is less than 9 months prior to Screening Visit date).
- Treatment with any other product within five times the expected half-life of the product (time from last treatment date to Screening Visit date is at least 4115 times the half-life of the given product).
- Treatment that can alter visual acuity between Screening and Baseline (e.g., periorbital injections.)
Trial locations and contacts
11 sites in 8 countries.
11 sites in 8 countries
United States4 sites
Johns Hopkins University, Wilmer Eye Institute
Baltimore, Maryland, 21287
Harvard Univ., Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of California San Francisco
San Francisco, California, 94158
Brazil1 site
INRET Clínica e Centro de Pesquisa
Belo Horizonte, Minas Gerais, 30150-270
Canada1 site
University of Toronto, Hospital for Sick Children
Toronto, Ontario, M5G0A4
France1 site
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DGOS CIC1423
Paris, 75012
Germany1 site
University of Tuebingen, Centre for Ophthalmology
Tübingen, 72076
About this study
The Gyrate Atrophy Ocular and Systemic Study characterizes the natural history of ornithine levels and retinal degeneration (RD) associated with disease-causing OAT variants in the presence of standard care dietary treatment regimens over 4 years. The research goal is to understand the impact of OAT mutations on plasma ornithine levels and retinal degeneration. Funding Source- FDA OOPD
Read the detailed description
Gyrate atrophy is a rare inherited chorioretinal degeneration that is associated with hyperornithinemia, an inborn error of metabolism caused by autosomal recessive mutations in the ornithine aminotransferase (OAT) gene. Gyrate atrophy is characterized by childhood-onset nyctalopia and sharply demarcated areas of chorioretinal atrophy that initially involve the midperipheral fundus. The atrophic areas typically coalesce and enlarge towards the posterior pole in the second and third decades of life, leading to severe visual field constriction and vision loss if left untreated. The current standard care treatment of gyrate atrophy is an arginine restricted diet that is implemented in practice using dietary protein restriction with essential amino acid supplementation. However, dietary treatment is highly burdensome on patients and negatively impacts quality of life such that only about ~20% of patients are able to comply. Strict adherence to dietary protein restriction (particularly through adolescence), essential amino acid supplementation, and nutritional management of body weight especially during intercurrent illness and pregnancy are among the challenges of treatment. Periods of suboptimal dietary control led to plasma ornithine elevation and progressive chorioretinal degeneration.
Investigators are developing gene therapy as a potential one-time treatment that could arrest disease progression while avoiding or reducing the need for dietary treatment. To facilitate a future interventional gene therapy clinical trial, there is a need to evaluate natural history of and the relationship between potential clinical trial outcome measures.
The objectives of the OAT gene natural history study are as follows:
- Natural History
- Characterize the natural history of retinal degeneration associated with disease-causing OAT variants in the presence of standard care dietary treatment regimens over four (4) years, using functional, structural, and patient-reported outcome measures.
- Characterize the natural history of ornithine levels associated with disease-causing OAT variants in the presence of standard care dietary treatment regimens over four (4) years.
- Determine within-patient variability of ornithine levels associated with disease-causing OAT variants in the presence of standard care dietary treatment regimens over four (4) years.
- Evaluate inter-eye correlation on ocular measures.
- Metabolic-Structure-Function Relationships
- Explore relationship of structural outcomes with functional outcomes in individuals with disease-causing OAT variants.
- Explore relationship of plasma ornithine levels with structural and functional outcomes in individuals with disease-causing OAT variants.
- Identify Rapid Progressors
- Explore possible risk factors (genotype, phenotype, environmental, comorbidities, and dietary therapy/supplements) for progression of the functional, structural, and patient-reported outcome measures over four (4) years in individuals with disease-causing OAT variants.
- Explore possible risk factors (genotype, phenotype, environmental, comorbidities, and dietary therapy/supplements) for ornithine levels over four (4) years in individuals with disease-causing OAT variants.
The expected impact of the OAT gene natural history study is to inform a future interventional clinical trial design and implementation, including the following:
- Determine within-patient variability of ornithine levels.
- Develop quantitative measures of progression of the area of preserved retina and establish its reproducibility, sensitivity to change, and relationship with other measures.
- Establish rates of progression of retinal degeneration on all functional, structural, and patient-reported outcome measures, and determine which measures are most sensitive to change.
- Determine primary time points and duration for a planned future treatment trial.
- Use variability and inter-eye correlation of outcomes for trial sample size calculations.
- Identify candidates for the future trial, including eligibility criteria based on risk factors and cut points for severity of disease most likely to benefit from treatment.
- Establish study procedures and workflows for practical implementation of the same testing procedures in a future trial.
- Conditions
- Gyrate Atrophy, Gyrata of Choroid and Retina; Atrophy, Ornithine-δ-aminotransferase, OAT, Chorioretinal Degeneration
- Keywords
- Gyrate Atrophy, OAT
- Medical subject headings
- Gyrate Atrophy, Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Vision Cohort 1 | Criteria that must be met in the better eye* at the Screening Visit: visual acuity ETDRS letter score of 54 or more (approximate Snellen equivalent 20/80 or better) and visual field** diameter 10 degrees or more in every meridian of the central field The better eye is defined as the eye with the better Screening Visit ETDRS visual acuity. However, if both eyes have the same visual acuity, which is defined as the same Snellen equivalent, then the determination will be made at investigator discretion. In this scenario, the investigator will consider the eye with better fixation or clearer ocular media to permit highest quality retinal imaging. The visual field (VF) is defined as the clinically determined kinetic VF III4e performed within the last 18 months prior to the Screening Visit or performed on the day of the Screening Visit. | |
| Vision Cohort 2 | Criteria that must be met in the better eye* at the Screening Visit: visual acuity ETDRS letter score of 19-53 (approximate Snellen equivalent 20/100 - 20/400) OR visual acuity ETDRS letter score of 54 or more (approximate Snellen equivalent 20/80 or better) and visual field** diameter less than 10 degrees in any meridian of the central field. The better eye is defined as the eye with the better Screening Visit ETDRS visual acuity. However, if both eyes have the same visual acuity, which is defined as the same Snellen equivalent, then the determination will be made at investigator discretion. In this scenario, the investigator will consider the eye with better fixation or clearer ocular media to permit highest quality retinal imaging. The visual field (VF) is defined as the clinically determined kinetic VF III4e performed within the last 18 months prior to the Screening Visit or performed on the day of the Screening Visit. | |
| Vision Cohort 3 | Criteria that must be met in the better eye* at the Screening Visit: visual acuity ETDRS letter score of 18 or less (approximate Snellen equivalent 20/500 or worse). The better eye is defined as the eye with the better Screening Visit ETDRS visual acuity. However, if both eyes have the same visual acuity, which is defined as the same Snellen equivalent, then the determination will be made at investigator discretion. In this scenario, the investigator will consider the eye with better fixation or clearer ocular media to permit highest quality retinal imaging. The visual field (VF) is defined as the clinically determined kinetic VF III4e performed within the last 18 months prior to the Screening Visit or performed on the day of the Screening Visit. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Structural Outcome: Characterize Change using Quantitative Measures of Progression of the Area of Preserved Retina
Measured by Wide Field Fundus Autofluorescence (FAF)
Measured: Baseline and every year until study completion (4 years)
Structural Outcome: Characterize Change using Quantitative Measures of Progression of the Area of Preserved Retina (Use with FAF for assessments)
Measured by wide field color photography
Measured: Baseline and every year until study completion (4 years)
Metabolic Outcome: Characterize Change in Plasma Ornithine Level
Obtained by fasting plasma amino acids panel and evaluated by a central lab
Measured: Baseline and every year until study completion (4 years)
Metabolic Outcome: Characterize Change in Blood Spot Ornithine Level
Obtained by fasting blood spot test amino acids panel and evaluated by a central lab
Measured: Baseline and every 4 months until study completion (4 years)
Secondary outcomes (12)
Structural Outcome: Ellipsoid zone (EZ) area
Measured by Spectral Domain Optical Coherence Tomography (SD-OCT)
Measured: Baseline and every year until study completion (4 years)
Structural Outcome: Area of Post Subcapsular Cataract
Measured by Red Reflex Photography
Measured: Baseline and every year until study completion (4 years)
Structural Outcome: Foveal Avascular Zone (FAZ) Area and Macular Vessel Density
Measured by OCTA Ancillary Test at Subset of Sites
Measured: Baseline and every year until study completion (4 years)
Functional Outcome: Visual Field Sensitivity Measured with Quantitative Topographic Analysis (Hill of Vision)
Measured by Octopus 900 Pro
Measured: Screening visit and every year until study completion (4 years) with the exception of baseline.
Functional Outcome: Early Treatment of Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score
Measured on the Electronic Visual Acuity (EVA) system or ETDRS charts.
Measured: Screening visit and every year until study completion (4 years) with the exception of baseline.
Functional Outcome: Low Visual Acuity Test - for participants unable to see ETDRS letters
Measured on the Berkeley Rudimentary Vision Test (BRVT)
Measured: Screening visit and every year until study completion (4 years) with the exception of baseline.
Functional Outcome: ETDRS Best Corrected Low Luminance Visual Acuity Letter Score
Measured on the Electronic Visual Acuity (EVA) system or ETDRS charts.
Measured: Screening visit and every year until study completion (4 years) with the exception of baseline.
Functional Outcome: Change in Mean Retinal Sensitivity
Measured by Fundus-Guided Microperimetry (MP)
Measured: Baseline and every year until study completion (4 years)
Functional Outcome: Change in Full-Field Retinal Sensitivity
Measured by full-field stimulus threshold (FST) testing to blue, white, and red stimuli
Measured: Baseline and every year until study completion (4 years)
Functional Outcome: Change in Retinal Function
Measured by full-field electroretinogram (ERG) amplitudes and timing in response to rod- and cone-specific stimuli.
Measured: Baseline and every year until study completion (4 years)
Metabolic Outcome: Proline, lysine, glutamine, glutamate, arginine, and related metabolite: creatine and its precursor guanidinoacetate
Obtained by fasting plasma amino acids panel and evaluated by a central lab
Measured: Two (2) fasting plasma samples collected on two (2) different days, within ten (10) days of Baseline Visit date and every year until study completion (4 years)
Metabolic Outcome: Level of dietary protein control
Obtained from serum albumin sample evaluated by a central lab
Measured: Baseline and every year until study completion (4 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2022
- Study start21 Nov 2023
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gyrate AtrophyStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jaeb Center for Health Research
- Sponsor type
- University, hospital or other
- Collaborators
- Conquering Gyrate Atrophy Foundation, Foundation Fighting Blindness
- Responsible party
- Sponsor
- Investigators
- Mandeep S. Singh, MD, Study chair, John Hopkin's - Wilmer Eye InstituteDavid Valle, MD, Study chair, John Hopkin's - Wilmer Eye Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05312736
- Sponsor's protocol ID
- GYROS
- Other IDs
- R01FD007628
- Acronym
- GYROS
- Status last verified
- Oct 2026
- First submitted
- 28 Mar 2022
- Last updated
- 27 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: After the study is completed, the de-identified, archived data will be transmitted to and stored at the FFB Consortium Coordinating Center, under the supervision of Allison Ayala, for use by other researchers including those outside of the study.
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gyrate Atrophy Ocular and Systemic Study
- ClinicalTrials.gov ID
- NCT05312736
- Acronym / sponsor ID
- GYROS / GYROS
- Conditions
- Gyrate Atrophy, Gyrata of Choroid and Retina; Atrophy, Ornithine-δ-aminotransferase, OAT, Chorioretinal Degeneration
- Keywords
- Gyrate Atrophy, OAT
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Jaeb Center for Health ResearchUniversity, hospital or other
- Collaborators
- Conquering Gyrate Atrophy Foundation, Foundation Fighting Blindness
- Study start
- 21 Nov 2023 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 5 Apr 2022 (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.
The Gyrate Atrophy Ocular and Systemic Study characterizes the natural history of ornithine levels and retinal degeneration (RD) associated with disease-causing OAT variants in the presence of standard care dietary treatment regimens over 4 years. The research goal is to understand the impact of OAT mutations on plasma ornithine levels and retinal degeneration. Funding Source- FDA OOPD
Detailed description
Gyrate atrophy is a rare inherited chorioretinal degeneration that is associated with hyperornithinemia, an inborn error of metabolism caused by autosomal recessive mutations in the ornithine aminotransferase (OAT) gene. Gyrate atrophy is characterized by childhood-onset nyctalopia and sharply demarcated areas of chorioretinal atrophy that initially involve the midperipheral fundus. The atrophic areas typically coalesce and enlarge towards the posterior pole in the second and third decades of life, leading to severe visual field constriction and vision loss if left untreated. The current standard care treatment of gyrate atrophy is an arginine restricted diet that is implemented in practice using dietary protein restriction with essential amino acid supplementation. However, dietary treatment is highly burdensome on patients and negatively impacts quality of life such that only about ~20% of patients are able to comply. Strict adherence to dietary protein restriction (particularly through adolescence), essential amino acid supplementation, and nutritional management of body weight especially during intercurrent illness and pregnancy are among the challenges of treatment. Periods of suboptimal dietary control led to plasma ornithine elevation and progressive chorioretinal degeneration.
Investigators are developing gene therapy as a potential one-time treatment that could arrest disease progression while avoiding or reducing the need for dietary treatment. To facilitate a future interventional gene therapy clinical trial, there is a need to evaluate natural history of and the relationship between potential clinical trial outcome measures.
The objectives of the OAT gene natural history study are as follows:
- Natural History
- Characterize the natural history of retinal degeneration associated with disease-causing OAT variants in the presence of standard care dietary treatment regimens over four (4) years, using functional, structural, and patient-reported outcome measures.
- Characterize the natural history of ornithine levels associated with disease-causing OAT variants in the presence of standard care dietary treatment regimens over four (4) years.
- Determine within-patient variability of ornithine levels associated with disease-causing OAT variants in the presence of standard care dietary treatment regimens over four (4) years.
- Evaluate inter-eye correlation on ocular measures.
- Metabolic-Structure-Function Relationships
- Explore relationship of structural outcomes with functional outcomes in individuals with disease-causing OAT variants.
- Explore relationship of plasma ornithine levels with structural and functional outcomes in individuals with disease-causing OAT variants.
- Identify Rapid Progressors
- Explore possible risk factors (genotype, phenotype, environmental, comorbidities, and dietary therapy/supplements) for progression of the functional, structural, and patient-reported outcome measures over four (4) years in individuals with disease-causing OAT variants.
- Explore possible risk factors (genotype, phenotype, environmental, comorbidities, and dietary therapy/supplements) for ornithine levels over four (4) years in individuals with disease-causing OAT variants.
The expected impact of the OAT gene natural history study is to inform a future interventional clinical trial design and implementation, including the following:
- Determine within-patient variability of ornithine levels.
- Develop quantitative measures of progression of the area of preserved retina and establish its reproducibility, sensitivity to change, and relationship with other measures.
- Establish rates of progression of retinal degeneration on all functional, structural, and patient-reported outcome measures, and determine which measures are most sensitive to change.
- Determine primary time points and duration for a planned future treatment trial.
- Use variability and inter-eye correlation of outcomes for trial sample size calculations.
- Identify candidates for the future trial, including eligibility criteria based on risk factors and cut points for severity of disease most likely to benefit from treatment.
- Establish study procedures and workflows for practical implementation of the same testing procedures in a future trial.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Vision Cohort 1 | – | –Criteria that must be met in the better eye* at the Screening Visit: visual acuity ETDRS letter score of 54 or more (approximate Snellen equivalent 20/80 or better) and visual field** diameter 10 degrees or more in every meridian of the central field The better eye is defined as the eye with the better Screening Visit ETDRS visual acuity. However, if both eyes have the same visual acuity, which is defined as the same Snellen equivalent, then the determination will be made at investigator discretion. In this scenario, the investigator will consider the eye with better fixation or clearer ocular media to permit highest quality retinal imaging. The visual field (VF) is defined as the clinically determined kinetic VF III4e performed within the last 18 months prior to the Screening Visit or performed on the day of the Screening Visit. |
| Vision Cohort 2 | – | –Criteria that must be met in the better eye* at the Screening Visit: visual acuity ETDRS letter score of 19-53 (approximate Snellen equivalent 20/100 - 20/400) OR visual acuity ETDRS letter score of 54 or more (approximate Snellen equivalent 20/80 or better) and visual field** diameter less than 10 degrees in any meridian of the central field. The better eye is defined as the eye with the better Screening Visit ETDRS visual acuity. However, if both eyes have the same visual acuity, which is defined as the same Snellen equivalent, then the determination will be made at investigator discretion. In this scenario, the investigator will consider the eye with better fixation or clearer ocular media to permit highest quality retinal imaging. The visual field (VF) is defined as the clinically determined kinetic VF III4e performed within the last 18 months prior to the Screening Visit or performed on the day of the Screening Visit. |
| Vision Cohort 3 | – | –Criteria that must be met in the better eye* at the Screening Visit: visual acuity ETDRS letter score of 18 or less (approximate Snellen equivalent 20/500 or worse). The better eye is defined as the eye with the better Screening Visit ETDRS visual acuity. However, if both eyes have the same visual acuity, which is defined as the same Snellen equivalent, then the determination will be made at investigator discretion. In this scenario, the investigator will consider the eye with better fixation or clearer ocular media to permit highest quality retinal imaging. The visual field (VF) is defined as the clinically determined kinetic VF III4e performed within the last 18 months prior to the Screening Visit or performed on the day of the Screening Visit. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The target population for GYROS will be patients with gyrate atrophy associated with disease-causing variants in the OAT gene.
Key inclusion criteria (8 listed)
- Participants must meet all the following inclusion criteria at the Screening Visit in order to be eligible to enroll into the genetic screening phase.
- Willing to participate in the study and able to communicate consent during the consent process.
- Willing and able to complete all study visit assessments at each visit over the forty-eight (48) month study period. Age ≥ 12 years.
- At least 2 disease-causing variants in the OAT gene which are homozygous or heterozygous in trans, based on a report from a clinically certified lab, or a report from a research lab that has been pre-approved by the study Genetics Committee.
- At least 2 disease-causing variants in the OAT gene with unknown phase, based on a report from a clinically certified lab, or a report from a research lab that has been pre-approved by the study Genetics Committee, AND must meet both of the following phenotype criteria: .Classic fundus appearance of gyrate atrophy (based on investigator discretion) AND Elevated ornithine levels >300 μmol/L (documented on any prior lab report).
Key exclusion criteria (18 listed)
- Participants must not meet any of the following exclusion criteria at the Screening Visit in order to be eligible to enroll into the genetic screening phase.
- Single pathogenic or likely pathogenic genetic variants known to be associated with autosomal dominant retinitis pigmentosa/retinal dystrophy (AD, heterozygous), X-374 linked retinitis pigmentosa/retinal dystrophy (XL, hemizygous), or mitochondrial inheritance.
- Expected to enter experimental treatment trial at any time during this study. History of more than 1 year of cumulative treatment, at any time, with an agent associated with pigmentary retinopathy, including hydroxychloroquine, chloroquine, thioridazine, and deferoxamine. Note: Since this is a Natural History Study collecting data on the progression of Gyrate Atrophy, pregnant women will not be specifically excluded from participation.
- If either eye has any of the following ocular exclusion criteria at the Screening Visit, then the participant is not eligible to enroll into the genetic screening phase.
- Current vitreous hemorrhage.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Structural Outcome: Characterize Change using Quantitative Measures of Progression of the Area of Preserved Retina
Time frame: Baseline and every year until study completion (4 years)
Measured by Wide Field Fundus Autofluorescence (FAF)
Structural Outcome: Characterize Change using Quantitative Measures of Progression of the Area of Preserved Retina (Use with FAF for assessments)
Time frame: Baseline and every year until study completion (4 years)
Measured by wide field color photography
Metabolic Outcome: Characterize Change in Plasma Ornithine Level
Time frame: Baseline and every year until study completion (4 years)
Obtained by fasting plasma amino acids panel and evaluated by a central lab
Metabolic Outcome: Characterize Change in Blood Spot Ornithine Level
Time frame: Baseline and every 4 months until study completion (4 years)
Obtained by fasting blood spot test amino acids panel and evaluated by a central lab
12 secondary outcomes
Structural Outcome: Ellipsoid zone (EZ) area
Time frame: Baseline and every year until study completion (4 years)
Structural Outcome: Area of Post Subcapsular Cataract
Time frame: Baseline and every year until study completion (4 years)
Structural Outcome: Foveal Avascular Zone (FAZ) Area and Macular Vessel Density
Time frame: Baseline and every year until study completion (4 years)
Functional Outcome: Visual Field Sensitivity Measured with Quantitative Topographic Analysis (Hill of Vision)
Time frame: Screening visit and every year until study completion (4 years) with the exception of baseline.
Functional Outcome: Early Treatment of Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score
Time frame: Screening visit and every year until study completion (4 years) with the exception of baseline.
Functional Outcome: Low Visual Acuity Test - for participants unable to see ETDRS letters
Time frame: Screening visit and every year until study completion (4 years) with the exception of baseline.
Functional Outcome: ETDRS Best Corrected Low Luminance Visual Acuity Letter Score
Time frame: Screening visit and every year until study completion (4 years) with the exception of baseline.
Functional Outcome: Change in Mean Retinal Sensitivity
Time frame: Baseline and every year until study completion (4 years)
Functional Outcome: Change in Full-Field Retinal Sensitivity
Time frame: Baseline and every year until study completion (4 years)
Functional Outcome: Change in Retinal Function
Time frame: Baseline and every year until study completion (4 years)
Metabolic Outcome: Proline, lysine, glutamine, glutamate, arginine, and related metabolite: creatine and its precursor guanidinoacetate
Time frame: Two (2) fasting plasma samples collected on two (2) different days, within ten (10) days of Baseline Visit date and every year until study completion (4 years)
Metabolic Outcome: Level of dietary protein control
Time frame: Baseline and every year until study completion (4 years)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Foundation Fighting Blindness Public WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. After the study is completed, the de-identified, archived data will be transmitted to and stored at the FFB Consortium Coordinating Center, under the supervision of Allison Ayala, for use by other researchers including those outside of the study.
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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.
Mandeep S. Singh, MD study chair
John Hopkin's - Wilmer Eye Institute
David Valle, MD study chair
John Hopkin's - Wilmer Eye Institute
11 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Gyrate Atrophy and Gyrata of Choroid and Retina; Atrophy, run by Jaeb Center for Health Research at 11 sites in 8 countries.
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 8 inclusion and 18 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: under way, not looking for participants, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Brazil, Canada, Finland, France and 3 more countries. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Structural Outcome: Characterize Change using Quantitative Measures of Progression of the Area of Preserved Retina (time frame: Baseline and every year until study completion (4 years)). The study lists 4 primary outcomes in all. 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 27 Oct 2026.