The Effect of Arginine and Citrulline Supplementation on Endothelial Dysfunction in Mitochondrial Diseases
Condition: Mitochondrial Diseases
MeSH terms: Mitochondrial Diseases
Study type: Interventional

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.
    

Intervention name(s): Arginine; Citrulline
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Arginine is an amino acids; Citrulline is an amino acid
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment