The Effect of Arginine and Citrulline Supplementation on Endothelial Dysfunction in Mitochondrial Diseases
Primary Purpose
Mitochondrial Diseases
Status
Completed
Phase
Not Applicable
Locations
United Arab Emirates
Study Type
Interventional
Intervention
Arginine
Citrulline
Sponsored by
About this trial
This is an interventional treatment trial for Mitochondrial Diseases
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- Tawam Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Arginine
Citrulline
Arm Description
Endothelial function will be assessed before and after arginine supplementation
Endothelial function will be assessed before and after citrulline supplementation
Outcomes
Primary Outcome Measures
Reactive hyperemic index (RHI)
Reactive hyperemic index (RHI) which reflects endothelial function will be measured using the EndoPAT instrument
Secondary Outcome Measures
Plasma concentration levels of arginine and citrulline
Plasma arginine and citrulline levels will also be measured
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02809170
Brief Title
The Effect of Arginine and Citrulline Supplementation on Endothelial Dysfunction in Mitochondrial Diseases
Official Title
The Effect of Arginine and Citrulline Supplementation on Endothelial Dysfunction in Mitochondrial Diseases
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
June 2016 (undefined)
Primary Completion Date
June 2019 (Actual)
Study Completion Date
June 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tawam Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mitochondrial Diseases
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arginine
Arm Type
Active Comparator
Arm Description
Endothelial function will be assessed before and after arginine supplementation
Arm Title
Citrulline
Arm Type
Active Comparator
Arm Description
Endothelial function will be assessed before and after citrulline supplementation
Intervention Type
Dietary Supplement
Intervention Name(s)
Arginine
Intervention Description
Arginine is an amino acids
Intervention Type
Dietary Supplement
Intervention Name(s)
Citrulline
Intervention Description
Citrulline is an amino acid
Primary Outcome Measure Information:
Title
Reactive hyperemic index (RHI)
Description
Reactive hyperemic index (RHI) which reflects endothelial function will be measured using the EndoPAT instrument
Time Frame
2 year
Secondary Outcome Measure Information:
Title
Plasma concentration levels of arginine and citrulline
Description
Plasma arginine and citrulline levels will also be measured
Time Frame
2 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ayman W El-Hattab, MD
Organizational Affiliation
Tawam Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tawam Hospital
City
Al Ain
Country
United Arab Emirates
12. IPD Sharing Statement
Plan to Share IPD
Yes
Learn more about this trial
The Effect of Arginine and Citrulline Supplementation on Endothelial Dysfunction in Mitochondrial Diseases
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