PBA Use for Treatment of ATF6-/- Patients

NCT04041232 | Suspended Early Phase 1 DMC FDA Drug

• 1 other identifier: AAAR9833
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

ACHROMATOPSIA 7; Achromatopsia

Keywords

achromatopsia; PBA; ATF6; color blindness

Outcome Measures

Primary Outcomes (6)

• Changes in best corrected visual acuity (BCVA)

  to measure changes in vision at each time point

  Baseline, 1 month, 3 months, 6 months post-PBA use

• Changes in contrast sensitivity

  using Pelli Robson charts

  Baseline, 1 month, 3 months, 6 months post-PBA use

• Changes in color vision

  using D50

  Baseline, 1 month, 3 months, 6 months post-PBA use

• Changes in macular sensitivity

  using microperimetry (Nidek)

  Baseline, 1 month, 3 months, 6 months post-PBA use

• Changes in retinal imaging

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

  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

• Changes in Full-field Electroretinogram (ffERG) X

  to measure changes in rod and cone traces

  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

Secondary Outcomes (3)

• Changes in intraocular pressure

  Baseline, 1 month, 3 months, 6 months post-PBA use

• Changes in anterior segment

  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

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

  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

Study Arms (1)

PBA treatment of ATF6-/- Achromatopsia

EXPERIMENTAL

Patients will be monitored at the baseline visit, followed by a second and third visit that will be 1 and 3 months after the initial visit. Patients will complete a standard visual functioning questionnaire and undergo a complete ophthalmic evaluation at each visit. Other visual assessments will consist of color vision testing, contrast sensitivity, retinal imaging, and macular sensitivity testing using microperimetry. Full-field electroretinogram will also be performed at the baseline visit and after 1 and 3 months of PBA use. If improvement in retinal function is observed, an additional ophthalmic evaluation will be conducted after 6 months of PBA use. A blood draw will be performed at each visit to test for any indications of adverse effects from drug use.

Drug: PBA

Interventions

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).

Also known as: Glycerol Phenylbutyrate

PBA treatment of ATF6-/- Achromatopsia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients harboring mutations in ATF6 present with decreased retinal function

You may not qualify if:

• Patients who are minors
• Patients who are pregnant

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Color Vision Defects

Interventions

glycerol phenylbutyrate

Condition Hierarchy (Ancestors)

Vision Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Cone Dystrophy; Eye Diseases, Hereditary; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Stephen Tsang, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two patients will receive PBA as treatment for ATF6-/- Achromatopsia.

Study Record Dates

• First Submitted: July 31, 2019
• First Posted: August 1, 2019
• Study Start: April 8, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: September 12, 2025

Record last verified: 2025-09

Locations

US (1)