Trial of Oral Glutamine on Mitochondrial Function in CKD
Condition: Cardiovascular Disease; Sarcopenia; Endothelial Dysfunction; Muscle Mitochondrial Function; Kidney Disease
MeSH terms: Sarcopenia; Kidney Diseases; Cardiovascular Diseases
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary goal of proposed investigation is to study the impact of oral glutamine
      supplementation on muscle mitochondrial and endothelial cell function measured mitochondrial
      energetics and vascular function using 31P magnetic resonance spectroscopy and optical
      spectroscopy (MRS/OS) among persons with moderate-severe CKD. The secondary objective is to
      describe the impact of oral glutamine supplementation on mitochondrial metabolic profile as
      well as inflammatory and oxidative stress biomarkers among persons with chronic kidney
      disease.
    

Detailed description: 
      Chronic kidney disease is associated with endothelial cell dysfunction and muscle wasting
      contributing to the heightened risk of cardiovascular morbidity, mortality and functional
      limitation. Accumulation of toxins in renal disease may adversely impact endothelial cell
      nitric oxide bioavailability and endothelial Nitric Oxide Synthase (eNOS) function
      consequently heightening oxidative stress and suppressing mitochondrial biogenesis. To date
      no studies have investigated potential therapies for endothelial and muscle dysfunction in
      renal disease target mitochondrial metabolic and energetic processes.

      Animal studies of uremia underscore mitochondrial dysfunction as a potential precursor for
      endothelial dysfunction. In particular, uremia has been linked to a proteomic signature
      indicative of metabolic blockage of TCA cycle activity and fatty acid beta-oxidation. Both of
      these processes are localized to the mitochondria and may suggest that decreased
      mitochondrial mass or function may augur endothelial dysfunction in renal disease.

      Glutamine, an anaplerotic agent and precursor to the antioxidant glutathione, is a potential
      therapeutic agent bypassing the metabolic block associated with reduced TCA cycle and
      improving antioxidant reserve. The primary goal of proposed investigation is to study the
      impact of oral glutamine supplementation on muscle mitochondrial and endothelial cell
      function measured mitochondrial energetics and vascular function using 31P MRS/OS among
      persons with moderate-severe CKD. The secondary objective is to describe the impact of oral
      glutamine supplementation on mitochondrial metabolic profile as well as inflammatory and
      oxidative stress biomarkers among persons with chronic kidney disease.
    

Intervention name(s): First Intervention (14 days); Washout (3 weeks); Second Intervention (14 days)
Intervention type(s): Dietary Supplement; Other; Dietary Supplement
Intervention description(s): Oral Glutamine or Maltodextrin for 2 weeks; No study product is taken prior to beginning crossover; Oral Glutamine or Maltodextrin for 2 weeks
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Glutamine; Chronic Kidney Disease