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

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ClinicalTrials.gov Identifier: NCT02809170
Recruitment Status : Completed
First Posted : June 22, 2016
Last Update Posted : March 18, 2020
Sponsor:
Information provided by (Responsible Party):
Ayman El-Hattab, Tawam Hospital

Tracking Information
First Submitted Date  ICMJE June 15, 2016
First Posted Date  ICMJE June 22, 2016
Last Update Posted Date March 18, 2020
Study Start Date  ICMJE June 2016
Actual Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 13, 2017)
Reactive hyperemic index (RHI) [ Time Frame: 2 year ]
Reactive hyperemic index (RHI) which reflects endothelial function will be measured using the EndoPAT instrument
Original Primary Outcome Measures  ICMJE
 (submitted: June 17, 2016)
Reactive hyperemic index (RHI) [ Time Frame: 1 year ]
Reactive hyperemic index (RHI) which reflects endothelial function will be measured using the EndoPAT instrument
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2017)
Plasma concentration levels of arginine and citrulline [ Time Frame: 2 year ]
Plasma arginine and citrulline levels will also be measured
Original Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2016)
Plasma concentration levels of arginine and citrulline [ Time Frame: 1 year ]
Plasma arginine and citrulline levels will also be measured
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of Arginine and Citrulline Supplementation on Endothelial Dysfunction in Mitochondrial Diseases
Official Title  ICMJE The Effect of Arginine and Citrulline Supplementation on Endothelial Dysfunction in Mitochondrial Diseases
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Mitochondrial Diseases
Intervention  ICMJE
  • Dietary Supplement: Arginine
    Arginine is an amino acids
  • Dietary Supplement: Citrulline
    Citrulline is an amino acid
Study Arms  ICMJE
  • Active Comparator: Arginine
    Endothelial function will be assessed before and after arginine supplementation
    Intervention: Dietary Supplement: Arginine
  • Active Comparator: Citrulline
    Endothelial function will be assessed before and after citrulline supplementation
    Intervention: Dietary Supplement: Citrulline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 29, 2018)
9
Original Estimated Enrollment  ICMJE
 (submitted: June 17, 2016)
10
Actual Study Completion Date  ICMJE June 2019
Actual Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 3 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Arab Emirates
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02809170
Other Study ID Numbers  ICMJE CED 343-14
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Ayman El-Hattab, Tawam Hospital
Study Sponsor  ICMJE Tawam Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ayman W El-Hattab, MD Tawam Hospital
PRS Account Tawam Hospital
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP