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Suspended

NCT Number: NCT04041232

PBA Use for Treatment of ATF6-/- Patients

Some patients with achromatopsia, an inherited disorder characterized by partial or complete loss of color vision, carry mutations in ATF6. ATF6 is a gene that is responsible for coding a protein that acts in response to endoplasmic reticulum (ER) stress. When the ATF6 protein is mutated, retinal function decreases, contributing to color blindness. The study aims to investigate whether an already FDA-approved drug, glycerol phenylbutyrate (PBA), can improve retinal function inpatients with achromatopsia caused by ATF6 mutations. Patients will be instructed to take three doses of PBA per day at equally divided time intervals and rounded up to the nearest 0.5 mL. The total dose of PBA will be 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day) and will not exceed 17.5 mL/day (19 g/day). Their condition will be monitored over the course of a minimum of 3 clinic visits that will consist of a number of retinal function tests, fundus examinations, and imaging procedures. Findings from the study could elucidate the potential for PBA to serve as a treatment for patients with ATF6-mediated a chromatopsia.

Why the study stopped: Administrative changes
Suspended

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Key information

Conditions

ACHROMATOPSIA 7 Achromatopsia Color Vision Defects Cone Dystrophy Eye Diseases Eye Diseases, Hereditary Nervous System Diseases Neurologic Manifestations Pathological Conditions, Signs and Symptoms Sensation Disorders Signs and Symptoms Vision Disorders

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Columbia University Irving Medical Center

New York, 10032, United States

About this study

ATF6 has been described as an endoplasmic reticulum (ER) stress-regulated transmembrane protein that activates the transcription of molecular chaperones in response to ER stress. Patients harboring mutations in ATF6 present with decreased retinal function and are diagnosed with achromatopsia. The investigator's research group has previously demonstrated that administration of glycerol phenylbutyrate (PBA), a fatty acid compound that facilitates protein folding, can lead to enhanced retinal function in mice that are homozygous for the ATF6 mutation. This study will investigate the effects of PBA administration in two patients who carry ATF6-/- mutations and a diagnosis of achromatopsia. Enrolled subjects will undergo a minimum of 3 clinic visits that consist of a complete ophthalmic examination (best-corrected visual acuity, intraocular pressure, anterior segment examination, slit lamp and binocular fundus examination), a visual functioning questionnaire, color vision tests, contrast sensitivity tests, retinal imaging (optical coherence tomography, short wavelength autofluorescence and near-infrared autofluorescence), a macular sensitivity test (Nidek microperimetry) and full-field electroretinogram (ffERG). A blood draw will be performed at each visit to test for any indications of adverse effects from drug use. Subjects will be instructed to take 3 doses of PBA per day, totaling to a dose of 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients harboring mutations in ATF6 present with decreased retinal function

Exclusion criteria

  • Patients who are minors
  • Patients who are pregnant

Treatment and study plan

PBA

Drug

Glycerol phenylbutyrate (PBA) is a triglyceride that consists of three molecules of phenylbutyrate linked to a glycerol backbone. It is a nitrogen-binding agent that has been approved by the Food and Drug Administration (FDA) for the treatment of urea cycle disorders. Oral supplementation of PBA demonstrated no severe side effects, and are found to be therapeutically effective in reducing ER stress. Patients will be instructed to take three doses of PBA per day at equally divided time intervals and rounded up to the nearest 0.5 mL. The total dose of PBA will be 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day) and will not exceed 17.5 mL/day (19 g/day).

Other names: Glycerol Phenylbutyrate

Primary outcomes

  1. Changes in best corrected visual acuity (BCVA)

    Time frame: Baseline, 1 month, 3 months, 6 months post-PBA use

    to measure changes in vision at each time point

  2. Changes in contrast sensitivity

    Time frame: Baseline, 1 month, 3 months, 6 months post-PBA use

    using Pelli Robson charts

  3. Changes in color vision

    Time frame: Baseline, 1 month, 3 months, 6 months post-PBA use

    using D50

  4. Changes in macular sensitivity

    Time frame: Baseline, 1 month, 3 months, 6 months post-PBA use

    using microperimetry (Nidek)

  5. Changes in retinal imaging

    Time frame: After 1 and 3 months of PBA use. If changes in retinal function is observed, an additional ophthalmic evaluation will be conducted after 6 months of PBA use

    including optical coherence tomography (OCT), short wavelength autofluorescence (SW-AF), and near-infrared autofluorescence (NIR-AF)

  6. Changes in Full-field Electroretinogram (ffERG) X

    Time frame: After 1 and 3 months of PBA use. If changes in retinal function is observed, an additional ophthalmic evaluation will be conducted after 6 months of PBA use

    to measure changes in rod and cone traces

Secondary outcomes

  1. Changes in intraocular pressure

    Time frame: Baseline, 1 month, 3 months, 6 months post-PBA use

    part of full ophthalmic evaluation

  2. Changes in anterior segment

    Time frame: After 1 and 3 months of PBA use. If changes in retinal function is observed, an additional ophthalmic evaluation will be conducted after 6 months of PBA use

    part of full ophthalmic evaluation

  3. Changes observed in posterior segment (slit lamp and binocular fundus examination)

    Time frame: After 1 and 3 months of PBA use. If changes in retinal function is observed, an additional ophthalmic evaluation will be conducted after 6 months of PBA use

    part of full ophthalmic evaluation

Sponsors and collaborators

Lead sponsor

Columbia University

Other

Registry information

Official study title

Evaluation of Glycerol Phenylbutyrate (PBA) Use in Endoplasmic Reticulum Stress Reduction in ATF6-/- Patients

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Aug 1, 2019
Registry last updated
Sep 11, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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