Trial of Nicotinamide Riboside and Co-enzyme Q10 in Chronic Kidney Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Cross-over Randomized Controlled Trial of Coenzyme Q10 or Nicotinamide Riboside in Chronic Kidney Disease

Conditions
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Sarcopenia, Chronic Kidney Disease, Frailty

Intervention / Treatment
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* Dietary Supplement: CoQ10
* Dietary Supplement: Nicotinamide riboside
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic kidney disease, defined in this study as an estimated glomerular filtration rate (eGFR) of <50ml/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration equation Exclusion Criteria: 6-minute walking distance >500meters Pregnancy Receiving renal replacement therapy (dialysis or kidney transplantation) Expectation to start dialysis within 6 months Insulin dependent diabetes mellitus Severe anemia: hemoglobin <8 g/dL Hyperkalemia: K >5.7 mEq/L Weight >300 lbs HIV End stage liver disease with cirrhosis Oxygen-dependent Chronic Obstructive Pulmonary Disease (COPD) Unable to walk unassisted from room to room in own house Institutionalization, or inability to consent Use of immunosuppressive medications (i.e. steroids, calcineurin inhibitors) Malignancy requiring active treatment or currently under surveillance (at the discretion of the investigator) Cardiac pacemaker Current participation in another interventional trial Non-English speaking Hospitalization for heart attack, stroke, or unstable cardiac chest pain within the previous 3 months (e.g. myocardial infarction, unstable angina, cerebrovascular accident) Any medical condition that the investigator feels would prevent the participant from safely completing the exercise-based outcome measurements. Baseline systolic blood pressure >170 or diastolic blood pressure >100 Persistent or permanent uncontrolled arrhythmia (at the discretion of the investigator)

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, placebo-controlled, cross-over trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CoQ10<br>Coenzyme Q10, 2 - 250 mg tablets twice a day (1000 mg total daily dose) for 6 weeks | Dietary Supplement: CoQ10<br>* CoQ10 tablet<br>* Other names: coenzyme Q10;|
| Active Comparator: Nicotinamide riboside<br>Nicotinamide riboside, 1 - 600 mg tablet twice a day (1200 mg total daily dose) for 6 weeks | Dietary Supplement: Nicotinamide riboside<br>* NR tablet<br>* Other names: NR;|
| Placebo Comparator: Placebo<br>Placebo, inactive sugar pill for 6 weeks | Dietary Supplement: Placebo<br>* Sugar pill designed to mimic coQ10 and NR<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal Aerobic Capacity- CoQ10 | The maximal aerobic capacity (oxygen uptake mL/min/kg body weight) during cycle ergometry at the end of each treatment period. | 6 weeks | 
| Work Efficiency | The work efficiency (oxygen uptake mL/min/kg body weight at a specified constant of 60 watts work rate for 3 minutes) during cycle ergometry at the end of each treatment period. This is reported as the work performed at 60 watts divided by the energy expended at 0 watts times 100, and reported on the percent scale.. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mitochondria, Antioxidants, CoQ10, Nicotinamide riboside, Ergometry, Fatigue, Aerobic capacity