Chronic Kidney Disease, Frailty, Sarcopenia
Conditions
Keywords
Mitochondria, Antioxidants, CoQ10, Nicotinamide riboside, Ergometry, Fatigue, Aerobic capacity
Brief 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.
Interventions
CoQ10 tablet
NR tablet
Sugar pill designed to mimic coQ10 and NR
Sponsors
Study design
Intervention model description
Randomized, placebo-controlled, cross-over trial
Eligibility
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal Aerobic Capacity- CoQ10 | 6 weeks | The maximal aerobic capacity (oxygen uptake mL/min/kg body weight) during cycle ergometry at the end of each treatment period. |
| Work Efficiency | 6 weeks | 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.. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo, Then Nicotinamide Riboside, Then CoQ10 Placebo, inactive sugar pill for 6 weeks; then washout for 1 week; then nicotinamide riboside, 1 - 600 mg tablet twice a day (1200 mg total daily dose) for 6 weeks; then washout for 1 week; then coenzyme Q10, 2 - 250 mg tablets twice a day (1000 mg total daily dose) for 6 weeks. | 4 |
| Placebo, Then CoQ10, Then Nicotinamide Riboside Placebo, inactive sugar pill for 6 weeks; then washout for 1 week; then coenzyme Q10, 2 - 250 mg tablets twice a day (1000 mg total daily dose) for 6 weeks; then washout for 1 week; then nicotinamide riboside, 1 - 600 mg tablet twice a day (1200 mg total daily dose) for 6 weeks. | 5 |
| Nicotinamide Riboside, Then Placebo, Then CoQ10 Nicotinamide riboside, 1 - 600 mg tablet twice a day (1200 mg total daily dose) for 6 weeks; then washout for 1 week; placebo, inactive sugar pill for 6 weeks; then washout for 1 week; then coenzyme Q10, 2 - 250 mg tablets twice a day (1000 mg total daily dose) for 6 weeks. | 5 |
| Nicotinamide Riboside, Then CoQ10, Then Placebo Nicotinamide riboside, 1 - 600 mg tablet twice a day (1200 mg total daily dose) for 6 weeks; then washout for 1 week; then coenzyme Q10, 2 - 250 mg tablets twice a day (1000 mg total daily dose) for 6 weeks; then washout for 1 week; placebo, inactive sugar pill for 6 weeks. | 4 |
| CoQ10, Then Placebo, Then Nicotinamide Riboside Coenzyme Q10, 2 - 250 mg tablets twice a day (1000 mg total daily dose) for 6 weeks; then washout for 1 week; then placebo, inactive sugar pill for 6 weeks; then washout for 1 week; then nicotinamide riboside, 1 - 600 mg tablet twice a day (1200 mg total daily dose) for 6 weeks. | 4 |
| CoQ10, Then Nicotinamide Riboside, Then Placebo Coenzyme Q10, 2 - 250 mg tablets twice a day (1000 mg total daily dose) for 6 weeks; then washout for 1 week; then nicotinamide riboside, 1 - 600 mg tablet twice a day (1200 mg total daily dose) for 6 weeks; then washout for 1 week; then placebo, inactive sugar pill for 6 weeks. | 4 |
| Total | 26 |
Baseline characteristics
| Characteristic | Placebo, Then CoQ10, Then Nicotinamide Riboside | Nicotinamide Riboside, Then Placebo, Then CoQ10 | Nicotinamide Riboside, Then CoQ10, Then Placebo | Placebo, Then Nicotinamide Riboside, Then CoQ10 | CoQ10, Then Placebo, Then Nicotinamide Riboside | CoQ10, Then Nicotinamide Riboside, Then Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 63.4 years STANDARD_DEVIATION 11.8 | 63.6 years STANDARD_DEVIATION 4.8 | 56.2 years STANDARD_DEVIATION 16.3 | 62.8 years STANDARD_DEVIATION 3 | 64.0 years STANDARD_DEVIATION 7.5 | 58.2 years STANDARD_DEVIATION 22.6 | 61.5 years STANDARD_DEVIATION 11.7 |
| Body mass index | 27.9 kg/m^2 STANDARD_DEVIATION 4.8 | 29.6 kg/m^2 STANDARD_DEVIATION 4 | 25.3 kg/m^2 STANDARD_DEVIATION 4.6 | 27.9 kg/m^2 STANDARD_DEVIATION 7.9 | 25.8 kg/m^2 STANDARD_DEVIATION 2.7 | 29.9 kg/m^2 STANDARD_DEVIATION 8.4 | 27.7 kg/m^2 STANDARD_DEVIATION 5.2 |
| eGFR per 2021 CKD-EPI | 39.3 mL/min/1.73m^2 STANDARD_DEVIATION 10.1 | 32.6 mL/min/1.73m^2 STANDARD_DEVIATION 7.8 | 34.6 mL/min/1.73m^2 STANDARD_DEVIATION 10.5 | 33.6 mL/min/1.73m^2 STANDARD_DEVIATION 10.5 | 45.2 mL/min/1.73m^2 STANDARD_DEVIATION 8 | 36.0 mL/min/1.73m^2 STANDARD_DEVIATION 4.5 | 37.0 mL/min/1.73m^2 STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 4 Participants | 4 Participants | 4 Participants | 3 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 3 Participants | 4 Participants | 4 Participants | 1 Participants | 4 Participants | 21 Participants |
| Region of Enrollment United States | 5 Participants | 5 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 26 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 0 Participants | 4 Participants | 3 Participants | 4 Participants | 16 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 0 / 25 | 1 / 25 | 2 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 | 0 / 25 |
Outcome results
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.
Time frame: 6 weeks
Population: Randomized participants that completed cycle ergometry following each treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CoQ10 | Maximal Aerobic Capacity- CoQ10 | 21.4 mL/min/kg | Standard Deviation 4.7 |
| Nicotinamide Riboside | Maximal Aerobic Capacity- CoQ10 | 20.7 mL/min/kg | Standard Deviation 4.7 |
| Placebo | Maximal Aerobic Capacity- CoQ10 | 20.7 mL/min/kg | Standard Deviation 4.8 |
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..
Time frame: 6 weeks
Population: Includes participants randomized and treated who complete cycle ergometry at the end of the corresponding treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CoQ10 | Work Efficiency | 33.3 Percent difference | Standard Deviation 4.2 |
| Nicotinamide Riboside | Work Efficiency | 32.5 Percent difference | Standard Deviation 5.1 |
| Placebo | Work Efficiency | 33.1 Percent difference | Standard Deviation 5.2 |