Trial of Nicotinamide Riboside and Co-enzyme Q10 in Chronic Kidney Disease (CoNR)
Primary Purpose
Chronic Kidney Disease, Sarcopenia, Frailty
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CoQ10
Nicotinamide riboside
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Kidney Disease focused on measuring Mitochondria, Antioxidants, CoQ10, Nicotinamide riboside, Ergometry, Fatigue, Aerobic capacity
Eligibility Criteria
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)
Sites / Locations
- University of Washington
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
CoQ10
Nicotinamide riboside
Placebo
Arm Description
Coenzyme Q10, 2 - 250 mg tablets twice a day (1000 mg total daily dose) for 6 weeks
Nicotinamide riboside, 1 - 600 mg tablet twice a day (1200 mg total daily dose) for 6 weeks
Placebo, inactive sugar pill for 6 weeks
Outcomes
Primary Outcome Measures
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.
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..
Secondary Outcome Measures
Full Information
NCT ID
NCT03579693
First Posted
June 25, 2018
Last Updated
December 13, 2022
Sponsor
University of Washington
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT03579693
Brief Title
Trial of Nicotinamide Riboside and Co-enzyme Q10 in Chronic Kidney Disease
Acronym
CoNR
Official Title
Cross-over Randomized Controlled Trial of Coenzyme Q10 or Nicotinamide Riboside in Chronic Kidney Disease
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
November 14, 2018 (Actual)
Primary Completion Date
April 26, 2021 (Actual)
Study Completion Date
April 26, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Disease, Sarcopenia, Frailty
Keywords
Mitochondria, Antioxidants, CoQ10, Nicotinamide riboside, Ergometry, Fatigue, Aerobic capacity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
Randomized, placebo-controlled, cross-over trial
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CoQ10
Arm Type
Active Comparator
Arm Description
Coenzyme Q10, 2 - 250 mg tablets twice a day (1000 mg total daily dose) for 6 weeks
Arm Title
Nicotinamide riboside
Arm Type
Active Comparator
Arm Description
Nicotinamide riboside, 1 - 600 mg tablet twice a day (1200 mg total daily dose) for 6 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo, inactive sugar pill for 6 weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
CoQ10
Other Intervention Name(s)
coenzyme Q10
Intervention Description
CoQ10 tablet
Intervention Type
Dietary Supplement
Intervention Name(s)
Nicotinamide riboside
Other Intervention Name(s)
NR
Intervention Description
NR tablet
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Sugar pill designed to mimic coQ10 and NR
Primary Outcome Measure Information:
Title
Maximal Aerobic Capacity- CoQ10
Description
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
Title
Work Efficiency
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bryan Kestenbaum, MD
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Baback Roshanravan, MD
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://kri.washington.edu
Description
Website for the Kidney Research Institute at the University of Washington
Learn more about this trial
Trial of Nicotinamide Riboside and Co-enzyme Q10 in Chronic Kidney Disease
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