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

Mitochondrial Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02809170
• Other study ID #: CED 343-14
• Status: Completed
• Phase: N/A
• Start date: June 2016
• Est. completion date: June 2019

Study information

• Verified date: March 2020
• Source: Tawam Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The investigators will study 10 children with mitochondrial diseases and 10 healthy control children. The investigators will study control children to be able compare the results of children with mitochondrial diseases to control healthy children. Therefore, the investigators will study control children only once to compare these results to the results of children with mitochondrial diseases at baseline. To assess the effect of arginine and citrulline on children with mitochondrial diseases, the investigators need to assess children with mitochondrial diseases four times. First time as baseline. Then children with mitochondrial diseases will be randomized to receive either oral arginine or citrulline at a dose of 500 mg/kg/day divided in 3 doses daily for 2 weeks after which a second assessment will be performed. Oral arginine or citrulline will be discontinued and after a two-week washout period another baseline assessment will be done. After that, the child will be started on oral citrulline (if the participant received arginine the first time) or arginine (if the participant received citrulline the first time) at a dose of 500 mg/kg/day divided in 3 doses daily for 2 weeks after which a fourth assessment will be done.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: June 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Years to 18 Years

Eligibility

Inclusion Criteria:

1. Diagnosis of mitochondrial disease with multi-organ disease involving neurological and/or muscular systems.

2. The diagnosis must be confirmed either molecularly (identifying mutations known to be associated with mitochondrial diseases) or by respiratory chain assay abnormalities.

Exclusion Criteria:

1. Have acute illness or physical disability interfering with ability to undergo the study procedures.

2. Known to have other factors that are known to result in endothelial dysfunction including hypertension, hyperlipidemia, and diabetes.

Related Conditions & MeSH terms

• Mitochondrial Diseases

Intervention

Dietary Supplement:
• Arginine
Arginine is an amino acids
• Citrulline
Citrulline is an amino acid

Locations

Country	Name	City	State
United Arab Emirates	Tawam Hospital	Al Ain

Sponsors (1)

Lead Sponsor	Collaborator
Tawam Hospital

Country where clinical trial is conducted

United Arab Emirates, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reactive hyperemic index (RHI)	Reactive hyperemic index (RHI) which reflects endothelial function will be measured using the EndoPAT instrument	2 year
Secondary	Plasma concentration levels of arginine and citrulline	Plasma arginine and citrulline levels will also be measured	2 year