L-Citrulline Dose Finding Safety Study in MELAS

  • End date
    Dec 6, 2023
  • participants needed
  • sponsor
    Baylor College of Medicine
Updated on 6 May 2022


The main purpose of this study is to determine the safest maximum dose of an amino acid, citrulline, which will be used as potential treatment for adult patients with a disorder of energy metabolism called Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS). Once established, this dose will be used in a future clinical trial.


The human body is made of many cells and each cell contains many mitochondria. Mitochondria are called the powerhouses of the cell, because they produce the energy needed for a cell to be healthy and function the way it is meant to.

Diseases of the mitochondria affect the way the tissues and cells of the body make and use energy, and can affect almost all the different organs of the body like the brain and the muscles.

MELAS syndrome is one of the mitochondrial diseases; patients with this disease have different complications including stroke like episodes, headache, muscle weakness, fatigue, and hearing loss. One of the factors contributing to complications seen in patients with MELAS syndrome, in particular the stroke like episodes, is decreased amount of an element called nitric oxide. This element is made in the bodies from an amino acid called arginine. Amino acids are the building blocks of proteins. Proteins make the muscles in the bodies, and they are present in meat, chicken and fish.

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

The lack of nitric oxide could cause constriction of blood vessels in the brain making it easier for these patients to have a metabolic stroke. The amino acid citrulline is a foundation for nitric oxide. In earlier studies, the investigator has found that there is more production of nitric oxide in the body when participants affected with MELAS take L-citrulline.

Condition MELAS Syndrome
Treatment L-citrulline
Clinical Study IdentifierNCT03952234
SponsorBaylor College of Medicine
Last Modified on6 May 2022


Yes No Not Sure

Inclusion Criteria

Clinical diagnosis of MELAS (stroke-like events, seizures, exercise intolerance or muscle weakness)
Subject must be aged 18 to 65 years
The m.3243A>G mutation in the MTTL1 gene
Elevated plasma lactate (>2.2 mmol/L) at the baseline visit
Negative urine pregnancy test, if applicable
Score of 26 or higher on the Montreal Cognitive Assessment (MOCA). -

Exclusion Criteria

Evidence of acute illness or physical disability that may interfere with their ability to undergo the study
Tobacco use
Orthostatic hypotension defined as a decrease in systolic blood pressure of 20 mm Hg, or a decrease in diastolic blood pressure of 10 mm Hg, between one and three minutes of standing when compared with blood pressure from the sitting or supine position
Presence of the following signs or symptoms in the past 12 months at grade 3 or higher based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03: hypotension, syncope, dizziness, blurred vision, fatigue, concentration impairment, nausea, vomiting, diarrhea, hypoglycemia, or headache
> 2 seizures in week prior to baseline visit
Hypotension defined as systolic blood pressure ≤ 90 mm Hg or diastolic blood pressure ≤ 60 mm Hg
Arginine supplementation within one week prior to baseline visit
Inability to travel to the study site
Subjects with no evidence of neurological disease, muscle weakness, or exercise intolerance
Subjects with evidence of moderate to severe renal impairment ( eGFR < 60 mL/min/1.73 m2 )
Subjects with poor cognitive ability to provide consent and to understand and report hypoglycemia
Unwillingness of sexually active female subjects of childbearing age to practice reliable methods of contraception
Intake of drugs that increase NO synthesis, vasodilators, or amino acid supplements that cannot be stopped during the study period
Positive urine pregnancy test
Score of less than 26 on the Montreal Cognitive Assessment (MOCA). -
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note