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Trial record 6 of 49 for:    Recruiting, Not yet recruiting, Available Studies | kidney disease | NIDDK

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

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ClinicalTrials.gov Identifier: NCT03579693
Recruitment Status : Recruiting
First Posted : July 6, 2018
Last Update Posted : December 6, 2018
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Bryan Kestenbaum, University of Washington

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.


Condition or disease Intervention/treatment Phase
Chronic Kidney Disease Sarcopenia Frailty Dietary Supplement: CoQ10 Dietary Supplement: Nicotinamide riboside Dietary Supplement: Placebo Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Randomized, placebo-controlled, cross-over trial
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Cross-over Randomized Controlled Trial of Coenzyme Q10 or Nicotinamide Riboside in Chronic Kidney Disease
Actual Study Start Date : November 14, 2018
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: CoQ10
Coenzyme Q10, 2 - 250 mg tablets twice a day (1000 mg total daily dose) for 6 weeks
Dietary Supplement: CoQ10
CoQ10 tablet
Other Name: coenzyme Q10

Active Comparator: Nicotinamide riboside
Nicotinamide riboside, 1 - 600 mg tablet twice a day (1200 mg total daily dose) for 6 weeks
Dietary Supplement: Nicotinamide riboside
NR tablet
Other Name: NR

Placebo Comparator: Placebo
Placebo, inactive sugar pill for 6 weeks
Dietary Supplement: Placebo
Sugar pill designed to mimic coQ10 and NR




Primary Outcome Measures :
  1. Maximal Aerobic Capacity- CoQ10 [ Time Frame: 6 weeks ]
    The maximal aerobic capacity (oxygen update mL/min/kg body weight) during cycle ergometry at the end of the coenzyme Q10 treatment period.

  2. Maximal Aerobic Capacity- NR [ Time Frame: 6 weeks ]
    The maximal aerobic capacity (oxygen update mL/min/kg body weight) during cycle ergometry at the end of the nicotinamide riboside treatment period.

  3. Maximal Aerobic Capacity- Placebo [ Time Frame: 6 weeks ]
    The maximal aerobic capacity (oxygen update mL/min/kg body weight) during cycle ergometry at the end of the placebo treatment period.

  4. Work Efficiency- CoQ10 [ Time Frame: 6 weeks ]
    The work efficiency (oxygen update mL/min/kg body weight at a specified constant work rate for 3 minutes) during cycle ergometry at the end of the coenzyme Q10 treatment period.

  5. Work Efficiency- NR [ Time Frame: 6 weeks ]
    The work efficiency (oxygen update mL/min/kg body weight at a specified constant work rate for 3 minutes) during cycle ergometry at the end of the nicotinamide riboside treatment period.

  6. Work Efficiency- Placebo [ Time Frame: 6 weeks ]
    The work efficiency (oxygen update mL/min/kg body weight at a specified constant work rate for 3 minutes) during cycle ergometry at the end of the placebo treatment period.


Secondary Outcome Measures :
  1. Peripheral Blood Mononuclear Cell (PBMC) mitochondrial energetics- coQ10 [ Time Frame: 6 weeks ]
    Reserve capacity (pmol of oxygen consumed/min) at the end of the coenzyme Q10 treatment period,measured by the difference between basal oxygen consumption and maximal uncoupled oxygen consumption from isolated monocytes and lymphocytes.

  2. PBMC mitochondrial energetics- NR [ Time Frame: 6 weeks ]
    Reserve capacity (pmol of oxygen consumed/min) at the end of the nicotinamide riboside treatment period, measured by the difference between basal oxygen consumption and maximal uncoupled oxygen consumption from isolated monocytes and lymphocytes.

  3. PBMC mitochondrial energetics- Placebo [ Time Frame: 6 weeks ]
    Reserve capacity (pmol of oxygen consumed/min) at the end of the placebo treatment period, measured by the difference between basal oxygen consumption and maximal uncoupled oxygen consumption from isolated monocytes and lymphocytes.

  4. Fatigue- CoQ10 [ Time Frame: 6 weeks ]
    Self-reported fatigue assessed by the score on the Patient-reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue Short Form 17a at the end of the coenzyme Q10 treatment period. Each item is scaled from 1 to 5 (1='never' and 5='always'), yielding a total between 22 to 85.

  5. Fatigue- NR [ Time Frame: 6 weeks ]
    Self-reported fatigue assessed by the score on the PROMIS Cancer Fatigue Short Form 17a at the end of the nicotinamide riboside treatment period. Each item is scaled from 1 to 5 (1='never' and 5='always'), yielding a total between 22 to 85.

  6. Fatigue- Placebo [ Time Frame: 6 weeks ]
    Self-reported fatigue assessed by the score on the PROMIS Cancer Fatigue Short Form 17a at the end of the placebo treatment period. Each item is scaled from 1 to 5 (1='never' and 5='always'), yielding a total between 22 to 85.

  7. Physical Function- CoQ10 [ Time Frame: 6 weeks ]
    Self-reported physical function abilities assessed by the score on the PROMIS Physical Function Short Form 20a at the end of the coQ10 treatment period. Each item is scaled from 1 to 5 (1='unable' and 5='without difficulty'), yielding a total between 20 to 100.

  8. Physical Function- NR [ Time Frame: 6 weeks ]
    Self-reported physical function abilities assessed by the score on the PROMIS Physical Function Short Form 20a at the end of the nicotinamide riboside treatment period. Each item is scaled from 1 to 5 (1='unable' and 5='without difficulty'), yielding a total between 20 to 100.

  9. Physical Function- Placebo [ Time Frame: 6 weeks ]
    Self-reported physical function abilities assessed by the score on the PROMIS Physical Function Short Form 20a at the end of the placebo treatment period. Each item is scaled from 1 to 5 (1='unable' and 5='without difficulty'), yielding a total between 20 to 100.

  10. Heart Failure Symptoms- CoQ10 [ Time Frame: 6 weeks ]
    Self-reported symptoms of heart failure assessed by the score on the Kansas City Heart Failure Questionnaire at the end of the coenzyme Q10 treatment period. Each item is scaled from 1 to 5, or 1 to 6 (1 indicates highest level of symptoms and 5 or 6 indicates the least level of symptoms), yielding a total between 0 to 100.

  11. Heart Failure Symptoms- NR [ Time Frame: 6 weeks ]
    Self-reported symptoms of heart failure assessed by the score on the Kansas City Heart Failure Questionnaire at the end of the nicotinamide riboside treatment period. Each item is scaled from 1 to 5, or 1 to 6 (1 indicates highest level of symptoms and 5 or 6 indicates the least level of symptoms), yielding a total between 0 to 100.

  12. Heart Failure Symptoms- Placebo [ Time Frame: 6 weeks ]
    Self-reported symptoms of heart failure assessed by the score on the Kansas City Heart Failure Questionnaire at the end of the placebo treatment period. Each item is scaled from 1 to 5, or 1 to 6 (1 indicates highest level of symptoms and 5 or 6 indicates the least level of symptoms), yielding a total between 0 to 100.

  13. Oxidative Stress: F2-isoprostanes- CoQ10 [ Time Frame: 6 weeks ]
    Level of serum F2-isoprostanes at the end of the coenzyme Q10 treatment period. Measured in pg/mL of serum.

  14. Oxidative Stress: F2-isoprostanes- NR [ Time Frame: 6 weeks ]
    Level of serum F2-isoprostanes at the end of the nicotinamide riboside treatment period. Measured in pg/mL of serum.

  15. Oxidative Stress: F2-isoprostanes- Placebo [ Time Frame: 6 weeks ]
    Level of serum F2-isoprostanes at the end of the placebo treatment period. Measured in pg/mL of serum.

  16. Oxidative Stress: Isofurans- CoQ10 [ Time Frame: 6 weeks ]
    Level of serum isofurans at the end of the coenzyme Q10 treatment period. Measured in pg/mL of serum.

  17. Oxidative Stress: Isofurans- NR [ Time Frame: 6 weeks ]
    Level of serum isofurans at the end of the nicotinamide riboside treatment period. Measured in pg/mL of serum.

  18. Oxidative Stress: Isofurans- Placebo [ Time Frame: 6 weeks ]
    Level of serum isofurans at the end of the placebo treatment period. Measured in pg/mL of serum.

  19. Inflammation: Interleukin (IL)-6- CoQ10 [ Time Frame: 6 weeks ]
    Level of serum IL-6 at the end of the coenzyme Q10 treatment period. Measured in pg/mL of serum.

  20. Inflammation: IL-6- NR [ Time Frame: 6 weeks ]
    Level of serum IL-6 at the end of the nicotinamide riboside treatment period. Measured in pg/mL of serum.

  21. Inflammation: IL-6- Placebo [ Time Frame: 6 weeks ]
    Level of serum IL-6 at the end of the placebo treatment period. Measured in pg/mL of serum.

  22. Inflammation: C-reactive Protein (CRP)- CoQ10 [ Time Frame: 6 weeks ]
    Level of serum C-reactive protein at the end of the coenzyme Q10 treatment period. Measured in pg/mL of serum.

  23. Inflammation: CRP- NR [ Time Frame: 6 weeks ]
    Level of serum C-reactive protein at the end of the nicotinamide riboside treatment period. Measured in pg/mL of serum.

  24. Inflammation: CRP- Placebo [ Time Frame: 6 weeks ]
    Level of serum C-reactive protein at the end of the placebo treatment period. Measured in pg/mL of serum.

  25. Metabolomics Plasma Profile- CoQ10 [ Time Frame: 6 weeks ]
    Targeted metabolomics profile of plasma, using liquid chromatography and high resolution mass spectroscopy, investigating fold changes in log-transformed metabolites (unitless), at the end of the coenzyme Q10 treatment period.

  26. Metabolomics Plasma Profile- NR [ Time Frame: 6 weeks ]
    Targeted metabolomics profile of plasma, using liquid chromatography and high resolution mass spectroscopy, investigating fold changes in log-transformed metabolites (unitless), at the end of the nicotinamide riboside treatment period.

  27. Metabolomics Plasma Profile- Placebo [ Time Frame: 6 weeks ]
    Targeted metabolomics profile of plasma, using liquid chromatography and high resolution mass spectroscopy, investigating fold changes in log-transformed metabolites (unitless), at the end of the placebo treatment period.

  28. Metabolomics Urine Profile- CoQ10 [ Time Frame: 6 weeks ]
    Targeted metabolomics profile of urine, using liquid chromatography and high resolution mass spectroscopy, investigating fold changes in log-transformed metabolites (unitless), at the end of the coenzyme Q10 treatment period.

  29. Metabolomics Urine Profile- NR [ Time Frame: 6 weeks ]
    Targeted metabolomics profile of urine, using liquid chromatography and high resolution mass spectroscopy, investigating fold changes in log-transformed metabolites (unitless), at the end of the nicotinamide riboside treatment period.

  30. Metabolomics Urine Profile- Placebo [ Time Frame: 6 weeks ]
    Targeted metabolomics profile of urine, using liquid chromatography and high resolution mass spectroscopy, investigating fold changes in log-transformed metabolites (unitless), at the end of the placebo treatment period.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   30 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03579693


Contacts
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Contact: Nicole Robinson, BS 206-897-4749 nrr3@uw.edu
Contact: Connor Henry, BA 206-734-6568 henryc8@uw.edu

Locations
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United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98104
Contact: Kidney Research Institute    206-616-8574    info@kri.washington.edu   
Sponsors and Collaborators
University of Washington
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Bryan Kestenbaum, MD University of Washington
Principal Investigator: Baback Roshanravan, MD University of Washington

Additional Information:
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Responsible Party: Bryan Kestenbaum, Professor, School of Medicine: Department of Medicine: Nephrology, University of Washington
ClinicalTrials.gov Identifier: NCT03579693     History of Changes
Other Study ID Numbers: STUDY00004998
R01DK101509 ( U.S. NIH Grant/Contract )
First Posted: July 6, 2018    Key Record Dates
Last Update Posted: December 6, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Bryan Kestenbaum, University of Washington:
Mitochondria
Antioxidants
CoQ10
Nicotinamide riboside
Ergometry
Fatigue
Aerobic capacity
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Nervous System Diseases
Pathological Conditions, Anatomical
Sarcopenia
Frailty
Muscular Atrophy
Neuromuscular Manifestations
Neurologic Manifestations
Atrophy
Signs and Symptoms
Pathologic Processes
Coenzyme Q10
Niacinamide
Niacin
Nicotinic Acids
Ubiquinone
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Vitamin B Complex
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents