L-Citrulline Dose Finding Safety Study in MELAS

• Status: Recruiting
• Trial end date: 2023-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Collaborators: Columbia University; National Institutes of Health (NIH); University of South Florida
• Treatments: Nitric Oxide

Criteria

Inclusion Criteria:

1. Clinical diagnosis of MELAS (stroke-like events, seizures, or both).

2. Subject must be aged 18 to 65 years.

3. The m.3243A>G mutation in the MTTL1 gene.

4. Elevated plasma lactate (>2.2 mmol/L) at the baseline visit.

5. Negative urine pregnancy test, if applicable.

6. Score of 26 or higher on the Montreal Cognitive Assessment (MOCA). -

Exclusion Criteria:

1. Evidence of acute illness or physical disability that may interfere with their ability to undergo the study.

2. Tobacco use

3. 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.

4. 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.

5. > 2 seizures in week prior to baseline visit.

6. Hypotension defined as systolic blood pressure ≤ 90 mm Hg or diastolic blood pressure ≤ 60 mm Hg.

7. Arginine supplementation within one month prior to baseline visit.

8. Inability to travel to the study site.

9. Subjects with no evidence of neurological disease.

10. Subjects with evidence of moderate to severe renal impairment ( eGFR < 60 mL/min/1.73 m2 ).

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

12. Unwillingness of sexually active female subjects of childbearing age to practice reliable methods of contraception.

13. Intake of drugs that increase NO synthesis, vasodilators, or amino acid supplements that cannot be stopped during the study period.

14. Positive urine pregnancy test.

15. Score of less than 26 on the Montreal Cognitive Assessment (MOCA). -