Valproate for the Treatment of Residual Amblyopia

NCT07226141 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IRB-P00051999
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine the efficacy of valproate as an adjunct therapy to treat amblyopia beyond the critical period in children aged 8-17 years who have amblyopia of ≥3 lines of interocular best-corrected (with glasses) visual acuity difference. The main questions it aims to answer are:

• Does valproate enable clinically meaningful and durable visual recovery from amblyopia?
• Do valproate-treated patients show a change in amblyopic eye visual acuity (lines)? Participants will undergo daily patching for 2 hours (standard of care) plus the addition of valproate or placebo for a total of 16 weeks.

Conditions

Amblyopia; Amblyopia Unilateral; Amblyopia, Anisometropic; Amblyopia Strabismic

Keywords

Amblyopia; valproate; valproic acid; pediatric; lazy eye; Histone deacetylase Inhibitor; HDAC; patching; eye patch; visual acuity; visual impairment; critical period; children; ophthalmology

Outcome Measures

Primary Outcomes (1)

• Amblyopic Eye Best-Corrected Visual Acuity (BCVA)

  Change in visual acuity of the amblyopic eye after 8 weeks of treatment with valproate plus patching versus placebo plus patching.

  The comparison will be made between the randomized groups at the 8-week visit, prior to cross-over.

Secondary Outcomes (5)

• Proportion of patients with resolved amblyopia

  8 weeks

• Durability of amblyopic eye visual acuity response

  8 weeks

• Change in stereoacuity

  8 weeks and 16 weeks

• Quality of life measures using the Pediatric Eye Questionnaire (PedEyeQ)

  Change from baseline at 8 weeks and 16 weeks.

• Tolerability and Safety of Valproate

  Assessed throughout the study duration at 1,2, 4, 6, 8, 9, 10, 12, 14 and 16 weeks.

Study Arms (2)

Arm 1 - Placebo first

PLACEBO COMPARATOR

Participants randomized to Arm 1 will receive oral placebo (250 mg twice daily) in combination with 2 hours of prescribed daily patching for 8 weeks. At the 8-week visit, participants will cross over to oral valproate at an initial dose of 15 mg/kg/day divided twice daily, while continuing the prescribed 2 hours of daily patching for an additional 8 weeks. Dose escalation of valproate up to 30 mg/kg/day (or placebo to 500 mg mice daily) will be permitted at interim visits if visual acuity has not improved and no adverse effects are present. All study medication will be discontinued after 16 weeks, with patching also discontinued at that time.

Drug: Valproate; Drug: Placebo; Behavioral: Patch

Arm 2 - Valproate first

EXPERIMENTAL

Participants randomized to Arm 2 will receive oral valproate at an initial dose of 15 mg/kg/day divided twice daily, together with 2 hours of prescribed daily patching for 8 weeks. At the 8-week visit, participants will cross over to oral placebo (250 mg twice daily) while continuing 2 hours of daily patching for an additional 8 weeks. If visual acuity has not improved at interim visits and no adverse effects are observed, the valproate dose may be escalated up to 30 mg/kg/day during the initial treatment phase, or placebo increased to 500 mg twice daily during the cross-over phase. After 16 weeks, both study medication and patching will be discontinued.

Drug: Valproate; Drug: Placebo; Behavioral: Patch

Interventions

Valproate DRUG

Valproate is an anti-epileptic medication used in this study to treat amblyopia. Participants will receive valproate in oral tablet form. The dosage will be determined based on the participant's weight and age, following standard dosing guidelines for valproate. The medication will be administered daily for a duration of 8 weeks. Participants will be monitored for any adverse effects, and dosage adjustments will be made if necessary to ensure safety and tolerability.

Arm 1 - Placebo first; Arm 2 - Valproate first

Placebo DRUG

The placebo intervention consists of an inert substance designed to mimic the appearance and administration of valproate tablets. Participants in the placebo group will receive the placebo tablets daily for the same duration of 8 weeks. This control group will help to assess the efficacy of valproate by comparing outcomes between the valproate and placebo groups. Participants receiving the placebo will also be monitored for any adverse effects to ensure the study's integrity and participant safety.

Arm 1 - Placebo first; Arm 2 - Valproate first

Patch BEHAVIORAL

Patching is a standard treatment for amblyopia, involving the occlusion of the fellow eye to stimulate the amblyopic eye. Participants will be required to patch their fellow eye for 2 hours daily throughout the 16-week study period. The patching regimen aims to improve visual acuity in the amblyopic eye by encouraging its use. Compliance with the patching protocol will be monitored, and participants will be provided with instructions and support to ensure proper application and adherence to the treatment.

Arm 1 - Placebo first; Arm 2 - Valproate first

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 8-17 years
• Amblyopia associated with strabismus and/or anisometropia
• Criteria for strabismus: must meet at least one of the following:
• Heterotropia at distance and/or near with or without spectacle correction
• History of strabismus surgery
• Documented history of strabismus that is no longer present and felt by the investigator could have caused the amblyopia
• Criteria for anisometropia: must meet at least one of the following:
• ≥ 0.50 D difference in spherical equivalent between eyes
• ≥ 1.50 D difference in astigmatism in any meridian between the eyes
• Visual acuity measured in each eye within 7 days prior to enrollment using ETDRS protocol on a study certified visual acuity tester as follows:
• Amblyopic eye visual acuity of 20/40 - 20/400
• Sound eye acuity of ≥ 20/25.
• Current amblyopia treatment (other than spectacle correction)
• Subjects actively patching at the time of enrollment screening should continue patching through enrollment
• Visual acuity in amblyopic eye has not improved ≥ 1 line (5 letters) by the same testing method from a previous visit ≥ 8 weeks earlier while on treatment

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (1)

Boston Children's Waltham

Waltham, Massachusetts, 02453, United States

Location

Related Publications (54)

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MeSH Terms

Conditions

Amblyopia; Vision Disorders

Interventions

Valproic Acid; Transdermal Patch

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sensation Disorders; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Equipment and Supplies

Study Officials

• Eric D Gaier, MD, PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eric D Gaier, MD, PhD

CONTACT

617-355-6401; Eric.Gaier@childrens.harvard.edu

Peter Casey-Caplan, BA

CONTACT

Peter.Casey-Caplan@childrens.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants, caregivers, investigators, and study staff conducting outcome assessments are all masked to treatment assignment. Study medication (valproate or placebo) is dispensed in identical-appearing capsules and bottles prepared by the research pharmacy. Randomization is managed via a secure web-based system, and treatment codes are not accessible to investigators or participants. Unmasking may only occur in the event of a medical emergency when knowledge of the treatment assignment is essential for subject safety.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Ophthalmology

Model Details: This is a prospective, randomized, double-blind, placebo-controlled interventional study with a cross-over-like design. Participants (ages 8-17) are randomized 1:1 to receive either valproate plus patching followed by placebo plus patching, or placebo plus patching followed by valproate plus patching. Each phase lasts 8 weeks (16 weeks total). The model ensures all participants are exposed to valproate, increases efficiency in a small pilot sample, and allows assessment of durability of response after discontinuation. Randomization is stratified by amblyopia severity, and both participants and investigators are masked to treatment assignment.

Study Record Dates

• First Submitted: September 26, 2025
• First Posted: November 10, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: November 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: The individual participant data (IPD) and supporting information will be available to qualified researchers starting 6 months after the publication of the primary study results. The data will remain accessible for 5 years from the start date. Researchers must submit a formal request, which will be reviewed for ethical and scientific alignment. This plan ensures valuable data contributes to advancements in amblyopia treatment while maintaining confidentiality.
• Access Criteria: Who Will Be Able to Access: Qualified researchers from academic institutions, research organizations, and healthcare institutions will be able to access the IPD and supporting information. Access will be granted based on the submission and approval of a formal request. What They Will Be Able to Access: Researchers will have access to de-identified individual participant data, including: Demographic information Clinical outcomes Visual acuity measurements Stereoacuity results Quality of life assessments Adverse event reports How They Will Be Able to Access: Researchers must submit a formal request detailing their study purpose and intended use of the data. The request will be reviewed by our study team for ethical and scientific alignment. Approved researchers will be granted access to the data through a secure online repository that complies with data protection regulations. Access will be restricted to the approved research purposes, and data sharing with third parties will require

Locations

US (1)