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Trial record 10 of 185 for:    "Mitochondrial Diseases" OR "mitochondrial neurogastrointestinal encephalopathy disease"

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

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ClinicalTrials.gov Identifier: NCT02809170
Recruitment Status : Active, not recruiting
First Posted : June 22, 2016
Last Update Posted : December 3, 2018
Sponsor:
Information provided by (Responsible Party):
Ayman El-Hattab, Tawam Hospital

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.

Condition or disease Intervention/treatment Phase
Mitochondrial Diseases Dietary Supplement: Arginine Dietary Supplement: Citrulline Not Applicable

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 : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of Arginine and Citrulline Supplementation on Endothelial Dysfunction in Mitochondrial Diseases
Study Start Date : June 2016
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : December 2019


Arm Intervention/treatment
Active Comparator: Arginine
Endothelial function will be assessed before and after arginine supplementation
Dietary Supplement: Arginine
Arginine is an amino acids

Active Comparator: Citrulline
Endothelial function will be assessed before and after citrulline supplementation
Dietary Supplement: Citrulline
Citrulline is an amino acid




Primary Outcome Measures :
  1. Reactive hyperemic index (RHI) [ Time Frame: 2 year ]
    Reactive hyperemic index (RHI) which reflects endothelial function will be measured using the EndoPAT instrument


Secondary Outcome Measures :
  1. Plasma concentration levels of arginine and citrulline [ Time Frame: 2 year ]
    Plasma arginine and citrulline levels will also be measured



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Ages Eligible for Study:   3 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02809170


Locations
United Arab Emirates
Tawam Hospital
Al Ain, United Arab Emirates
Sponsors and Collaborators
Tawam Hospital
Investigators
Principal Investigator: Ayman W El-Hattab, MD Tawam Hospital

Responsible Party: Ayman El-Hattab, Consultant, Genetics and Metabolic, Tawam Hospital
ClinicalTrials.gov Identifier: NCT02809170     History of Changes
Other Study ID Numbers: CED 343-14
First Posted: June 22, 2016    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Additional relevant MeSH terms:
Mitochondrial Diseases
Metabolic Diseases