What side effects are associated with this type of intervention?

Treatments for MELAS Syndrome, particularly those involving amino acid supplements like citrulline, may cause gastrointestinal discomfort, including nausea, diarrhea, and bloating. There is also a potential risk of imbalances in amino acid levels, which could affect metabolic processes.

What prior FDA approvals exist?

There is no specific mention of prior FDA approvals for the treatment of MELAS Syndrome in the provided context. However, the study on citrulline, an amino acid aimed at improving energy metabolism, suggests a focus on metabolic support as a therapeutic strategy. Treatments for MELAS often aim to enhance mitochondrial function and energy production, which is consistent with the use of amino acids like citrulline.

What other types of research exist?

Promising novel alternatives to Citrulline for MELAS Syndrome patients include: 1) Sodium phenylbutyrate/taurursodiol, which has shown potential in improving mitochondrial function and energy metabolism. 2) Antisense oligonucleotide therapies, which target specific genetic mutations and have shown promise in other neurodegenerative diseases. 3) High-caloric nutrition, which has been studied for its impact on survival and quality of life in mitochondrial disorders. These alternatives should be discussed with a healthcare provider to determine the best individualized treatment plan.

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Amino Acid

L-Citrulline for MELAS Syndrome

Phase 1

Waitlist Available

Led By FERNANDO SCAGLIA, M.D

Research Sponsored by Baylor College of Medicine

Eligibility Criteria Checklist

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

Must have

Subject must be aged 18 to 65 years

Clinical diagnosis of MELAS (stroke-like events, seizures, exercise intolerance or muscle weakness)

Must not have

Subjects with poor cognitive ability to provide consent and to understand and report hypoglycemia

Inability to travel to the study site

Timeline

Screening 3 weeks

Treatment Varies

Follow Up one week

Awards & highlights

No Placebo-Only Group

Summary

This trial aims to find the safest dose of citrulline for adults with MELAS, a condition that affects energy production in cells. Citrulline can help increase nitric oxide levels, improving blood flow and potentially reducing stroke risk. Citrulline has been shown to improve nitric oxide production and may have a better therapeutic effect than arginine in treating MELAS syndrome.

Who is the study for?

Adults aged 18-65 with MELAS Syndrome, a specific genetic mutation (m.3243A>G), and elevated plasma lactate can join this trial. They must have cognitive health to pass the MOCA test and not be pregnant or using tobacco. Those with recent seizures, no neurological symptoms, severe kidney issues, or taking certain medications are excluded.

What is being tested?

The study is testing the safety of different doses of L-Citrulline in adults with MELAS Syndrome to find the highest safe dose for future research. Participants will receive increasing amounts of L-Citrulline to establish its maximum tolerable level without significant side effects.

What are the potential side effects?

Potential side effects may include hypotension (low blood pressure), dizziness, blurred vision, fatigue, difficulty concentrating, nausea, vomiting, diarrhea, hypoglycemia (low blood sugar), or headache as indicated by previous criteria for adverse events.

Eligibility Criteria

Inclusion Criteria

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

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I am between 18 and 65 years old.

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I have been diagnosed with MELAS, experiencing symptoms like stroke-like events, seizures, or muscle weakness.

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My genetic test shows I have the m.3243A>G mutation.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I can understand and report low blood sugar levels.

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I cannot travel to the study location.

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My cognitive test score is below 26.

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I do not have neurological disease, muscle weakness, or trouble exercising.

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I am taking medication or supplements that affect blood flow and cannot stop them for the study.

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I've had severe symptoms like fainting, dizziness, or headaches in the past year.

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I have had more than 2 seizures in the week before my first visit.

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I am not willing to use birth control.

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My kidney function is moderately to severely reduced.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ four weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~four weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and four weeks for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Establishment of the maximum tolerable dose of L-citrulline in patients with MELAS syndrome by measuring the incidence of dose limiting toxicities (DLTs)

Secondary study objectives

Changes effected by the use of citrulline in the concentration of plasma guanidino compounds

Changes effected by the use of citrulline in the micromolar concentration of plasma alanine and in the concentration of plasma lactate (expressed in millimole per liter)

Changes effected by the use of citrulline supplementation in the micromolar concentration of plasma amino acids citrulline, arginine, ornithine, and alanine levels.

+2 more

Side effects data

From 2021 Phase 2 trial • 65 Patients • NCT04570384

Infusion Site Reaction

Deep Vein Thrombosis

Dyspnoea

Clostridium Difficile Infection

Urinary Tract Infection

Staphylococcal Sepsis; Alpha Haemolytic Streptococcal Infection

Pain In Extremity

Skin Wound

Acute kidney injury

Cardiac failure; metabolic acidosis

Chest pain; Dyspnoea; COVID-19

Intracranial hemorrhage

Acute Myocardial Infarction

Status epilepticus

Syncope

Enterococcal Infection

Enterococcus Test Positive

Epistaxis

Hypoglycaemia

Hypoxia

Tachycardia

Ventricular Extrasystoles

100%

80%

60%

40%

20%

Study treatment Arm

Placebo Arm

IV L-Citrulline (Turnobi) Arm

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Dose finding safety studyExperimental Treatment1 Intervention

In this study, the highest acceptable dose of an amino acid called citrulline will be established in people who have a mitochondrial disorder. Previous research conducted by several groups including our center at Baylor College of Medicine has determined that there is a deficiency of a compound called nitric oxide in people affected with MELAS.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

L-Citrulline

2023

Completed Phase 2

~350

0 / 12Eligibility 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

MELAS Syndrome is a mitochondrial disorder that impairs energy metabolism, leading to symptoms like muscle weakness, neurological deficits, and lactic acidosis. Common treatments aim to enhance mitochondrial function and energy production. For instance, L-Citrulline, an amino acid, is being studied for its potential to improve energy metabolism by increasing nitric oxide production, which can enhance blood flow and oxygen delivery to tissues. This is crucial for MELAS patients as it may help alleviate symptoms by improving cellular energy levels and reducing the frequency and severity of stroke-like episodes.

Effect of testosterone on whole body amino acid utilization in myotonic dystrophy.Leucine-Rich Diet Modulates the Metabolomic and Proteomic Profile of Skeletal Muscle during Cancer Cachexia.Melatonin attenuates chronic immobilization stress-induced muscle atrophy in rats: Influence on lactate-to-pyruvate ratios and Na+/K+ ATPase activity.