The Effect of Arginine and Citrulline Supplementation on Endothelial Dysfunction in Mitochondrial Diseases

NCT02809170 | Completed DMC

• 1 other identifier: CED 343-14
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Mitochondrial diseases occur due to inadequate energy production. In addition, nitric oxide (NO) deficiency occurs in mitochondrial diseases. The endothelial layer of blood vessels functions in maintaining blood vessels patency through producing NO which relaxes vascular smooth muscles and therefore maintains the patency of blood vessels and adequate blood perfusion. In mitochondrial diseases, endothelial cells fail to perform their normal function in maintaining the patency of blood vessels (endothelial dysfunction) because of the inability to produce enough NO. Endothelial dysfunction results in decreased blood perfusion in different organs which can contribute to the complications seen in mitochondrial diseases. The amino acids arginine and citrulline act as NO precursors and can increase NO production. In this study we hypothesize that due to the inability to produce enough NO patients with mitochondrial diseases have endothelial dysfunction that will improve after arginine or citrulline supplementation. The investigators will assess endothelial function using peripheral arterial tonometry before and after arginine or citrulline supplementation. The investigators expect that arginine and citrulline supplementation will improve endothelium function. This will support the therapeutic use of arginine and citrulline in mitochondrial diseases.

Conditions

Mitochondrial Diseases

Outcome Measures

Primary Outcomes (1)

• Reactive hyperemic index (RHI)

  Reactive hyperemic index (RHI) which reflects endothelial function will be measured using the EndoPAT instrument

  2 year

Secondary Outcomes (1)

• Plasma concentration levels of arginine and citrulline

  2 year

Study Arms (2)

Arginine

ACTIVE COMPARATOR

Endothelial function will be assessed before and after arginine supplementation

Dietary Supplement: Arginine

Citrulline

ACTIVE COMPARATOR

Endothelial function will be assessed before and after citrulline supplementation

Dietary Supplement: Citrulline

Interventions

Arginine DIETARY_SUPPLEMENT

Arginine is an amino acids

Arginine

Citrulline DIETARY_SUPPLEMENT

Citrulline is an amino acid

Citrulline

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of mitochondrial disease with multi-organ disease involving neurological and/or muscular systems.
• The diagnosis must be confirmed either molecularly (identifying mutations known to be associated with mitochondrial diseases) or by respiratory chain assay abnormalities.

You may not qualify if:

• Have acute illness or physical disability interfering with ability to undergo the study procedures.
• Known to have other factors that are known to result in endothelial dysfunction including hypertension, hyperlipidemia, and diabetes.

Sponsors & Collaborators

• Tawam Hospital: lead

Study Sites (1)

Tawam Hospital

Al Ain City, United Arab Emirates

Location

MeSH Terms

Conditions

Mitochondrial Diseases

Interventions

Arginine; Citrulline

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Ayman W El-Hattab, MD

  Tawam Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant, Genetics and Metabolic

Study Record Dates

• First Submitted: June 15, 2016
• First Posted: June 22, 2016
• Study Start: June 1, 2016
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: March 18, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share

Locations

AE (1)