Trial of Nicotinamide Riboside and Co-enzyme Q10 in Chronic Kidney Disease
Condition: Chronic Kidney Disease; Sarcopenia; Frailty
MeSH terms: Sarcopenia; Kidney Diseases; Renal Insufficiency, Chronic; Frailty
Study type: Interventional
Phase: Phase 2

Summary: 
      Chronic kidney disease is associated with the loss of skeletal muscle mass and function. This
      process detrimentally impacts mobility, functional independence, and quality of life.
      Mounting evidence suggests that chronic kidney disease impairs skeletal muscle functioning by
      injuring mitochondria, the central energy producing units of cells.

      Potential treatment options to restore mitochondrial function include aerobic and weight
      bearing exercise and medications that directly improve mitochondrial energetics.
      Unfortunately, exercise programs may be difficult to implement in people who have chronic
      diseases, such as kidney disease.. Coenzyme Q10 (coQ10) and nicotinamide riboside (NR) are
      naturally occurring supplements that can directly improve mitochondrial efficiency. Both
      compounds help mitochondria produce more energy while generating less waste.

      The primary purpose of this study is to test whether coQ10 and NR can improve muscle function
      among people with chronic kidney disease. What we learn in this study may help us better
      understand the mechanisms of skeletal muscle impairment among people with kidney disease and
      ultimately improve their ability to be active and independent.
    

Detailed description: 
      Sarcopenia (decreased muscle mass or function) is common in patients with chronic kidney
      disease (CKD) patients with direct impacts on their metabolic and clinical outcomes. Existing
      evidence and the investigator's preliminary data suggest that mitochondrial dysfunction is a
      key underlying mechanism of sarcopenia in CKD. However, the ability of treatments to modify
      mitochondrial functioning in CKD patients is unknown. Coenzyme Q10 (coQ10) and nicotinamide
      riboside (NR) are naturally occurring supplements that reduce oxidative stress and restore
      substrate delivery to mitochondria, respectively.

      Both processes have the potential to increase mitochondrial energy production with direct
      consequences for many metabolic and physical processes, including:

        -  aerobic capacity

        -  work efficiency

        -  mitochondrial energetics

        -  fatigue

        -  physical function

        -  inflammation

        -  oxidative stress

        -  heart failure symptoms

        -  metabolomics

      These outcomes will assessed in all study participants who enroll in the trial. Addressing
      these knowledge gaps is necessary to shed new light on the pathophysiology of sarcopenia in
      CKD and suggest future interventions that reduce morbidity and mortality.

      This is a randomized, placebo-controlled, double-blind crossover trial of coQ10 and NR
      treatments. Participants will receive coQ10 (1000 mg daily), NR (1200 mg daily), or placebo
      each for six-weeks in random order with a 7-day washout between treatment periods. The
      primary outcomes are aerobic capacity and muscle work efficiency, measured during cycle
      ergometry.
    

Intervention name(s): CoQ10; Nicotinamide riboside; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): CoQ10 tablet; NR tablet; Sugar pill designed to mimic coQ10 and NR
Other intervention name(s): coenzyme Q10; NR
Intervention MeSH terms: Niacinamide; Niacin; Nicotinic Acids; Coenzyme Q10
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Randomized, placebo-controlled, cross-over trial
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Mitochondria; Antioxidants; CoQ10; Nicotinamide riboside; Ergometry; Fatigue; Aerobic capacity