Gyrate Atrophy Ocular and Systemic Study

NCT05312736 | Active Not Recruiting

• 2 other identifiers: GYROSR01FD007628
• Study Type: observational
• Target: 46
• Locations: 8 countries
• Sites: 11

Brief 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. The research goal is to understand the impact of OAT mutations on plasma ornithine levels and retinal degeneration. Funding Source- FDA OOPD

Conditions

Gyrate Atrophy; Gyrata of Choroid and Retina; Atrophy; Ornithine-δ-aminotransferase; OAT; Chorioretinal Degeneration

Keywords

Gyrate Atrophy; OAT

Outcome Measures

Primary Outcomes (4)

• Structural Outcome: Characterize Change using Quantitative Measures of Progression of the Area of Preserved Retina

  Measured by Wide Field Fundus Autofluorescence (FAF)

  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

  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

  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

  Baseline and every 4 months until study completion (4 years)

Secondary Outcomes (12)

• Structural Outcome: Ellipsoid zone (EZ) area

  Baseline and every year until study completion (4 years)

• Structural Outcome: Area of Post Subcapsular Cataract

  Baseline and every year until study completion (4 years)

• Structural Outcome: Foveal Avascular Zone (FAZ) Area and Macular Vessel Density

  Baseline and every year until study completion (4 years)

• Functional Outcome: Visual Field Sensitivity Measured with Quantitative Topographic Analysis (Hill of Vision)

  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

  Screening visit and every year until study completion (4 years) with the exception of baseline.

Other Outcomes (2)

• Patient Reported Outcomes Adults 18 years or older

  Baseline and every two years until study completion (4 years)

• Patient Reported Outcomes Adolescents 12-17 years

  Baseline and every two years until study completion (4 years)

Study Arms (3)

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.

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The target population for GYROS will be patients with gyrate atrophy associated with disease-causing variants in the OAT gene.

You may qualify if:

• 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).
• 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).

You may not qualify if:

• 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.
• Current vitreous hemorrhage.
• 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.)

Sponsors & Collaborators

• Jaeb Center for Health Research: lead
• Conquering Gyrate Atrophy Foundation: collaborator
• Foundation Fighting Blindness: collaborator

Study Sites (11)

University of California San Francisco

San Francisco, California, 94158, United States

Location

Johns Hopkins University, Wilmer Eye Institute

Baltimore, Maryland, 21287, United States

Location

Harvard Univ., Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

INRET Clínica e Centro de Pesquisa

Belo Horizonte, Minas Gerais, 30150-270, Brazil

Location

University of Toronto, Hospital for Sick Children

Toronto, Ontario, M5G0A4, Canada

Location

Helsinki University Hospital

Helsinki, 00280, Finland

Location

Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DGOS CIC1423

Paris, 75012, France

Location

University of Tuebingen, Centre for Ophthalmology

Tübingen, 72076, Germany

Location

Vista Vision Eye Clinic

Brescia, 25123, Italy

Location

Moorfields Eye Hospital

London, UK EC1V 2PD, United Kingdom

Location

Related Links

• Foundation Fighting Blindness Public Website

Biospecimen

Retention: SAMPLES WITH DNA

blood samples and skin biopsy

MeSH Terms

Conditions

Gyrate Atrophy; Atrophy

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Choroid Diseases; Uveal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Mandeep S. Singh, MD

  John Hopkin's - Wilmer Eye Institute

  STUDY CHAIR

• David Valle, MD

  John Hopkin's - Wilmer Eye Institute

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2022
• First Posted: April 5, 2022
• Study Start: November 21, 2023
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 26, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: After manuscript is published
• Access Criteria: Users accessing data must enter an email address

Locations

DE (1); BR (1); CA (1); FR (1); FI (1); IT (1); US (4); GB (1)