Leucine Enriched Essential Amino Acid Powder as an Add-on to a Classic Ketogenic Diet in Refractory Epilepsy

Open Label, Single-Arm Study of the Safety and Tolerability of a Leucine Enriched Essential Amino Acid Powder as an Add-on to a Classic Ketogenic Diet in Refractory Epilepsy

The main purpose of this study is to evaluate the safety and tolerability of a Leucine-Enriched Essential Amino Acid (LEAA) Powder as an add-on to a classic ketogenic diet (KD) in pediatric and adult patients with refractory epilepsy.

Study Overview

• Status: Not yet recruiting
• Conditions: Drug Resistant Epilepsy; Refractory Epilepsy
• Intervention / Treatment: Drug: Leucine-Enriched Essential Amino Acid powder

Detailed Description

This is a single center, single-arm, open label study to evaluate the safety, tolerability, and nutritional effect of Leucine-Enriched Essential Amino Acid powder (LEAA) when added to classical KD in pediatric and adult patients whose epilepsy is insufficiently controlled on the diet. The study will enroll patients who have previously been compliant with their classical KD regimen for at least 28 days prior to enrollment and have experienced some response (≥40% reduction in seizures), but not complete response (<90% reduction in seizures) to dietary management with KD. Study duration is 84 days and will have 3 remote study visits (Baseline- Remote Visit 1, Dose Adjustment- Remote Visit 2, and Final- Remote Visit 3) and a pre-screening communication via telephone/video.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Carolyn Wilson; Email: cwilson41@mgh.harvard.edu
• Study Contact Backup: Name: Lydia Tsega, MD, MPH; Phone Number: 6177266524; Email: ltsega@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
      • Contact: Carolyn Wilson; Email: cwilson41@mgh.harvard.edu
      • Contact: Lydia Tsega, MD, MPH; Phone Number: 617-726-6524; Email: ltsega@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients ages 2 years and up at enrollment.
2. A diagnosis of epilepsy, with at least 2 seizures per week according to the parent/guardian report to study staff and investigator medical notes if applicable. All seizure types allowed.
3. Under stable treatment with a classic ketogenic diet (KD) regimen with a KD ratio ≥ 1:1, with or without antiseizure medications (ASMs), for at least 28 days with documented, partial response (≥40% reduction in seizures), but not a complete response (<90% reduction in seizures) based on patient medical records or parental report.
4. Patient and/or parent/caregiver able and willing to follow all study procedures and successfully complete the study.

Exclusion Criteria:

1. Patients who have changed their KD regimen or antiseizure medication (ASM) or vagus nerve stimulation (VNS) within the last 28 days.
2. Allergy, sensitivity to, or inability to metabolize any component of leucine enriched essential amino acid (LEAA).
3. Those who are pregnant or breastfeeding.
4. Patients who have received an investigational drug or product or participated in a drug study within 4 weeks before the first dose of leucine enriched essential amino acid (LEAA) powder.
5. Patients who have a clinically significant condition or have had either clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to the Baseline Visit 1, other than epilepsy, that would negatively impact study participation, collection of study data, or pose a risk to the patient including liver disease.
6. Patients with history of suicidal ideation in past 6-months and suicidal behavior in past 2-years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Leucine-Enriched Essential Amino Acid powder (LEAA); Leucine-Enriched Essential Amino Acid powder (LEAA) as an add-on to a classic ketogenic diet (KD)	Drug: Leucine-Enriched Essential Amino Acid powder; Leucine-Enriched Essential Amino Acid Powder will be orally/enterally administered by mixing in water or ketogenic formula.; Other Names: LEAA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events	Number of participants with treatment-related adverse events as reported by the trial participants.	Baseline, 3 weeks, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with improved nutritional status as assessed by weight.	Nutritional status will be assessed by measuring participants' weight in kilograms.	Baseline, 3 weeks, 12 weeks
Number of participants with improved nutritional status as assessed by body mass index (BMI).	Nutritional status will be assessed by measuring participants' weight in kilograms and height in meters to assess their body mass index (BMI).	Baseline, 3 weeks, 12 weeks
Number of participants with improved nutritional status as assessed by serum ketone and glucose level.	Serum ketone and glucose level will be measure before and after intake of investigational medicine.	At each visit and on next day

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in seizure frequency as assessed by seizure diary.	Daily record of seizure type, duration, and frequency on seizure diary will be used to measure seizure changes.	Baseline, 3 weeks, 12 weeks
Changes in behavior and cognitive function as assessed by a questionnaire.	Global assessment on behavior and cognitive function questionnaire will be used by study subject/parent/caregiver to assess behavior and cognitive function.	Baseline, 3 weeks, 12 weeks
Changes in seizure severity and overall health as assessed by a questionnaire.	Global assessment on seizure severity, and overall health questionnaire will be used by clinician/dietitian and study subject/parent/caregiver to assess changes in seizure severity and overall health.	Baseline, 3 weeks, 12 weeks

Collaborators and Investigators

• Sponsor: Elizabeth Anne Thiele
• Collaborators: Ajinomoto Co., Inc.; Ajinomoto USA, INC.
• Investigators: Principal Investigator: Elizabeth Thiele, MD, PhD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: April 16, 2024
• First Submitted That Met QC Criteria: April 23, 2024
• First Posted (Actual): April 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Ketogenic Diet; Refractory Epilepsy; Leucine-Enriched Essential Amino Acid
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Drug Resistant Epilepsy
• Other Study ID Numbers: 2023P003233

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No