Valproate for Lazy Eye

(VARA Trial)

Overseen By Peter Casey-Caplan, BA

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Boston Children's Hospital

Must not be taking: Seizure meds, Bipolar meds

Disqualifiers: Liver disease, Kidney disease, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether valproate, a medication, can improve vision in children and teens with amblyopia, commonly known as lazy eye, beyond the typical treatment window. Participants will continue their usual 2-hour daily eye patching and receive either valproate or a placebo to determine if the combination leads to better and lasting vision improvement. It suits those aged 8-17 who have been patching without significant improvement. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to explore this potential new therapy.

Do I need to stop my current medications for the trial?

You may need to stop certain medications, especially if you are taking any for seizures, bipolar disorder, or migraines, as these can interact with valproate. The trial does not specify a washout period, but it's important to discuss your current medications with the trial team.

Is there any evidence suggesting that valproate is likely to be safe for humans?

Research shows that valproate is usually well-tolerated, but some side effects may occur. Studies have found that more than 5% of people taking valproate experience side effects such as stomach pain, hair loss, blurry vision, and weakness. While these side effects are common, they do not affect everyone.

The FDA has already approved valproate for treating other conditions, indicating that its safety is well-understood. Doctors have extensive experience with the medication, which aids in managing any side effects that might arise.

Prospective trial participants should discuss these possible side effects with their doctor to make an informed decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for amblyopia?

Researchers are excited about valproate for treating lazy eye (amblyopia) because it offers a fresh approach compared to traditional methods like patching or atropine eye drops. Valproate is an anti-seizure medication that may enhance brain plasticity, potentially improving visual acuity by helping the brain's visual pathways adapt and strengthen. This mechanism is different from the standard treatments that primarily focus on blocking the dominant eye to force the weaker eye to work harder. If successful, valproate could offer a more direct and possibly faster way to enhance visual improvement in patients with lazy eye.

What evidence suggests that valproate might be an effective treatment for amblyopia?

Research suggests that valproate might help treat amblyopia (lazy eye) by increasing the brain's adaptability, potentially enhancing its ability to process visual information from the weaker eye. In this trial, participants will be randomized into two groups: one will receive valproate first, and the other will start with a placebo. Studies on adults with amblyopia have shown promising results, indicating that valproate can improve vision. Although these studies mainly focus on adults, they offer hope that valproate might also benefit children older than the usual treatment age. While direct evidence in children is still developing, valproate's mechanism provides a strong reason to believe it could be beneficial. ^{1 6 7 8 9}

Who Is on the Research Team?

Eric D Gaier, MD, PhD

Principal Investigator

Boston Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children aged 8-17 with lazy eye (amblyopia) who have a significant difference in vision between eyes and haven't improved with patching alone. They must have had an eye exam recently, wear the correct glasses, and be likely to follow the treatment plan. Kids can't join if they're very nearsighted, might get pregnant, or have certain health problems like liver disease or psychological issues.

Inclusion Criteria

Visual acuity measured in each eye within 7 days prior to enrollment using ETDRS protocol on a study certified visual acuity tester

Spectacle correction for measurement of enrollment visual acuity must meet specific criteria and be based on a cycloplegic refraction < 6 months old

Eye examination within 6 months prior to enrollment

Exclusion Criteria

Myopia > -6.00 D spherical equivalent

Known past or present mitochondrial/metabolic disorder

Known past or present psychological problems

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive either oral valproate or placebo with daily patching for 8 weeks

8 weeks

In-person visits at 1, 2, 4, 6, and 8 weeks

Treatment Phase 2

Participants cross over to the alternate treatment arm for an additional 8 weeks

8 weeks

In-person visits at 9, 10, 12, 14, and 16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Valproate

Trial Overview The study tests whether valproate can help improve vision in kids with lazy eye when added to standard treatment of wearing an eye patch for two hours daily. Over 16 weeks, participants will either receive valproate or a placebo while continuing their regular patching routine.

How Is the Trial Designed?

Group I: Arm 2 - Valproate first Experimental Treatment 3 Interventions

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.

Group II: Arm 1 - Placebo first Placebo Group 3 Interventions

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.

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07226141

Valproate for the Treatment of Residual Amblyopia Shared data will include demographic information, clinical outcomes, visual acuity measurements, stereoacuity results, quality of life ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3223381/

New Perspectives in Amblyopia Therapy on Adults: A Critical ... A pharmacological epigenetic treatment increasing histone acetylation (i.p. injection of valproic acid, VPA) emerged to be effective in adult ...

3. frontiersin.org frontiersin.org/journals/neural-circuits/articles/10.3389/fncir.2014.00082/full

Treatment of amblyopia in the adult: insights from a new ... This review will survey recent work regarding the impact of visual perceptual learning on amblyopia, with a special focus on a new experimental model.

4. researchgate.net researchgate.net/figure/Pharmacological-and-environmental-therapeutic-strategies-for-amblyopia-in-adulthood_fig1_51855944

Pharmacological and environmental therapeutic strategies ... Results According to the amblyopia EHR data elements, the data of physician and patient, examinations, website members, and members' roles were determined.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30456449/

Valproic acid exerts specific cellular and molecular anti- ... It is also potentially useful as anti-fibrotic therapy as it reduced collagen deposition in the post-operative conjunctiva.

6. htsyndication.com htsyndication.com/us-fed-news/article/clinical-trial%3A-valproate-for-the-treatment-of-residual-amblyopia/555770828

Valproate for the Treatment of Residual Amblyopia Brief Summary: The goal of this clinical trial is to determine the efficacy of valproate as an adjunct therapy to treat amblyopia beyond the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5678336/

The adverse effects of valproic acid on visual functions in the ... Clemson et al. examined 13 eyes before and after brief treatment (average 4 months) with VPA.[13] They found that nine eyes had improved VFA with treatment, ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/021168s048lbl.pdf

Reference ID: 5516838 - accessdata.fda.gov Most common adverse reactions (reported >5%) are abdominal pain, alopecia, amblyopia/blurred vision, amnesia, anorexia, asthenia, ataxia, back pain, bronchitis, ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1059131103000827

The effect of antiepileptic drugs on visual performance Visual disturbances are a common side-effect of many antiepileptic drugs. Non-specific retino- and neurotoxic visual abnormalities, that are often reported ...