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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT04041232
Other study ID # AAAR9833
Secondary ID
Status Not yet recruiting
Phase Early Phase 1
First received
Last updated
Start date May 2023
Est. completion date March 2024

Study information

Verified date March 2023
Source Columbia University
Contact Stephen Tsang, MD
Phone 212-342-1189
Email sht2@cumc.columbia.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

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).


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 2
Est. completion date March 2024
Est. primary completion date March 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Patients harboring mutations in ATF6 present with decreased retinal function Exclusion Criteria: - Patients who are minors - Patients who are pregnant

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
PBA
Glycerol phenylbutyrate (PBA) is a triglyceride that consists of three molecules of phenylbutrate 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).

Locations

Country Name City State
United States Edward S. Harkness Eye Institute New York New York

Sponsors (1)

Lead Sponsor Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary Changes in contrast sensitivity using Pelli Robson charts Baseline, 1 month, 3 months, 6 months post-PBA use
Primary Changes in color vision using D50 Baseline, 1 month, 3 months, 6 months post-PBA use
Primary Changes in macular sensitivity using microperimetry (Nidek) Baseline, 1 month, 3 months, 6 months post-PBA use
Primary 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
Primary 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 Changes in intraocular pressure part of full ophthalmic evaluation Baseline, 1 month, 3 months, 6 months post-PBA use
Secondary Changes in anterior segment part of full ophthalmic evaluation 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 Changes observed in posterior segment (slit lamp and binocular fundus examination) part of full ophthalmic evaluation 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
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