Skip to content

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

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

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03579693
Acronym
CoNR
Enrollment
26
Registered
2018-07-06
Start date
2018-11-14
Completion date
2021-04-26
Last updated
2023-01-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Kidney Disease, Frailty, Sarcopenia

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

DIETARY_SUPPLEMENTCoQ10

CoQ10 tablet

DIETARY_SUPPLEMENTNicotinamide riboside

NR tablet

DIETARY_SUPPLEMENTPlacebo

Sugar pill designed to mimic coQ10 and NR

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
CollaboratorNIH
University of Washington
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)

Intervention model description

Randomized, placebo-controlled, cross-over trial

Eligibility

Sex/Gender
ALL
Age
30 Years to 79 Years
Healthy volunteers
No

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

MeasureTime frameDescription
Maximal Aerobic Capacity- CoQ106 weeksThe maximal aerobic capacity (oxygen uptake mL/min/kg body weight) during cycle ergometry at the end of each treatment period.
Work Efficiency6 weeksThe 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

ArmCount
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
Total26

Baseline characteristics

CharacteristicPlacebo, Then CoQ10, Then Nicotinamide RibosideNicotinamide Riboside, Then Placebo, Then CoQ10Nicotinamide Riboside, Then CoQ10, Then PlaceboPlacebo, Then Nicotinamide Riboside, Then CoQ10CoQ10, Then Placebo, Then Nicotinamide RibosideCoQ10, Then Nicotinamide Riboside, Then PlaceboTotal
Age, Continuous63.4 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 index27.9 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-EPI39.3 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 Participants0 Participants0 Participants0 Participants0 Participants1 Participants1 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
5 Participants5 Participants4 Participants4 Participants4 Participants3 Participants25 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants2 Participants0 Participants0 Participants1 Participants0 Participants3 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants1 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants1 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
5 Participants3 Participants4 Participants4 Participants1 Participants4 Participants21 Participants
Region of Enrollment
United States
5 Participants5 Participants4 Participants4 Participants4 Participants4 Participants26 Participants
Sex: Female, Male
Female
3 Participants2 Participants0 Participants4 Participants3 Participants4 Participants16 Participants
Sex: Female, Male
Male
2 Participants3 Participants4 Participants0 Participants1 Participants0 Participants10 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 250 / 250 / 25
other
Total, other adverse events
0 / 251 / 252 / 25
serious
Total, serious adverse events
0 / 250 / 250 / 25

Outcome results

Primary

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.

ArmMeasureValue (MEAN)Dispersion
CoQ10Maximal Aerobic Capacity- CoQ1021.4 mL/min/kgStandard Deviation 4.7
Nicotinamide RibosideMaximal Aerobic Capacity- CoQ1020.7 mL/min/kgStandard Deviation 4.7
PlaceboMaximal Aerobic Capacity- CoQ1020.7 mL/min/kgStandard Deviation 4.8
p-value: 0.3395% CI: [-0.43, 1.31]Mixed Models Analysis
p-value: 0.9395% CI: [-0.9, 0.82]Mixed Models Analysis
Primary

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.

ArmMeasureValue (MEAN)Dispersion
CoQ10Work Efficiency33.3 Percent differenceStandard Deviation 4.2
Nicotinamide RibosideWork Efficiency32.5 Percent differenceStandard Deviation 5.1
PlaceboWork Efficiency33.1 Percent differenceStandard Deviation 5.2
p-value: 0.0595% CI: [-3.47, 0]Mixed Models Analysis
p-value: 0.4795% CI: [-2.28, 1.05]Mixed Models Analysis

Source: ClinicalTrials.gov · Data processed: Feb 9, 2026