What side effects are associated with this type of intervention?

Common treatments for encephalopathy with epilepsy and neurodevelopmental disorders include antiepileptic drugs (AEDs) such as sodium valproate, levetiracetam, and phenobarbital. Sodium valproate can cause side effects like weight gain, hair loss, tremors, and liver toxicity. Levetiracetam is generally well-tolerated but may lead to behavioral changes, fatigue, and dizziness. Phenobarbital can cause sedation, cognitive impairment, and dependency with long-term use. Glycerol phenylbutyrate, being studied for its potential to enhance the function of remaining proteins in monogenetic developmental epileptic encephalopathies, may have side effects such as gastrointestinal disturbances, headache, and fatigue, similar to other treatments aimed at metabolic modulation.

What prior FDA approvals exist?

FDA-approved treatments for encephalopathy with epilepsy and neurodevelopmental disorders include medications like cannabidiol (CBD) for Dravet syndrome, which targets drug-resistant seizures. Another example is stiripentol, used in combination with clobazam and valproate for Dravet syndrome, enhancing GABAergic activity. These treatments, like glycerol phenylbutyrate, aim to improve the function of remaining proteins or pathways affected by genetic mutations.

What other types of research exist?

Promising novel alternatives to glycerol phenylbutyrate for treating encephalopathy with epilepsy and neurodevelopmental disorders include antisense oligonucleotide therapies, gene therapy using viral vectors, and sodium benzoate for seizure management.

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Histone Deacetylase Inhibitor

Phenylbutyrate for Neurodevelopmental Disorders

Phase < 1

Waitlist Available

Led By Zachary Grinspan, MD

Research Sponsored by Weill Medical College of Cornell University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Is between 2 months and 17 years of age, inclusive.

Has normal renal function, with estimated glomerular filtration rate > 90 mL/minute/1.73 m2 at Screening (using the Chronic Kidney Disease Epidemiology Collaboration equation).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through december 2025 (1 - 5 years, depending on participant)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing glycerol phenylbutyrate, a medication that helps brain proteins work better, in children with severe genetic epilepsy and developmental delays. The goal is to see if it is safe and effective for these children.

Who is the study for?

This trial is for children aged 2 months to 17 years with specific genetic disorders causing epilepsy and developmental delays, such as STXBP1 Encephalopathy or SLC6A1 neurodevelopmental disorder. Participants need a confirmed diagnosis through genetic testing, normal heart rhythm on an EKG, and good kidney function. They should be in stable health apart from their neurological condition.

What is being tested?

The study tests the safety and tolerability of glycerol phenylbutyrate (Ravicti) in treating monogenetic developmental epileptic encephalopathies (DEEs). It aims to see if this medication can enhance the functioning of proteins affected by these genetic conditions.

What are the potential side effects?

While not explicitly listed here, potential side effects may include digestive issues since glycerol phenylbutyrate is processed by the liver and kidneys. As it's being tested for safety, monitoring will occur for any adverse reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am between 2 months and 17 years old.

Select...

My kidney function is normal, with a filtration rate above 90 mL/min.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through december 2025 (1 - 5 years, depending on participant)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through december 2025 (1 - 5 years, depending on participant)

This trial's timeline: 3 weeks for screening, Varies for treatment, and through december 2025 (1 - 5 years, depending on participant) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Long Term Adverse events (i.e., safety)

Percentage of doses taken by participants (i.e., tolerability)

Short Term Adverse events (i.e., safety)

Secondary study objectives

Plasma concentration of phenylbutyrate

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: SLC6A1 and STXBP1Experimental Treatment1 Intervention

Each participant will be enrolled for 14 weeks (4 weeks baseline, 8 weeks of drug exposure, and 2 weeks follow-up). After clinical assessment by the investigator if deemed safe and appropriate, and requested by the caregiver, participants may continue to receive the study medication ("extended use"), up to December 2025. Participants who remain on phenylbutyrate therapy will be followed quarterly through video visits, and yearly in-person visit. Participants who do not opt to remain on phenylbutyrate therapy will be weaned off the medication during the 2 week follow-up period.

Group II: Monogenetic Epileptic EncephalopathyExperimental Treatment1 Intervention

Each participant will be enrolled for 20 weeks (5 weeks baseline, 12 weeks of drug exposure, and 2 weeks follow-up) . After clinical assessment by the investigator if deemed safe and appropriate, and requested by the caregiver, participants may continue to receive the study medication ("extended use"), up to December 2025. Participants who remain on phenylbutyrate therapy will be followed quarterly through video visits, and yearly in-person visit. Participants who do not opt to remain on phenylbutyrate therapy will be weaned off the medication during the 2 week follow-up period.

0 / 2Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Encephalopathy with Epilepsy and Neurodevelopmental Disorder, such as Glycerol Phenylbutyrate, work by enhancing the function of remaining proteins that are otherwise deficient or dysfunctional due to genetic mutations. These treatments aim to stabilize or improve the activity of these proteins, thereby reducing the frequency and severity of seizures and supporting better neurodevelopmental outcomes. This is crucial for patients as it can lead to improved cognitive function, reduced seizure burden, and overall better quality of life. By targeting the underlying molecular deficiencies, these treatments offer a more precise and potentially effective approach compared to broader anti-seizure medications.

Neonatal seizures and their treatment.