Sodium Bicarbonate and Mitochondrial Energetics in Persons With CKD
Senergy-CKD
Randomized Cross-over Trial of Sodium Bicarbonate on Muscle Mitochondrial Energetics and Physical Endurance in Chronic Kidney Disease and Metabolic Acidosis
2 other identifiers
interventional
80
1 country
2
Brief Summary
Skeletal muscle metabolic health is critical for mobility and an underrecognized target of metabolic acidosis in chronic kidney disease. Impaired muscle mitochondrial metabolism underlies poor physical endurance increasing the risk of mobility disability. The proposed project will use precise in vivo tools to study the pathophysiology of poor physical endurance in a clinical trial treating metabolic acidosis among persons living with chronic kidney disease.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Sep 2023
Typical duration for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 8, 2021
CompletedFirst Posted
Study publicly available on registry
July 30, 2021
CompletedStudy Start
First participant enrolled
September 8, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
May 6, 2026
May 1, 2026
3.3 years
July 8, 2021
May 4, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
muscle mitochondrial oxidative capacity by 31P MRS
We will use 31P MRS to evaluate the concentration of phospho-creatine (PCr) and other phosphate-energy carrier molecules in limb muscles. After one minute of basal resting measurements, patients will be asked to perform two knee extensions every second against ankle weights 5-10% of the maximal voluntary contraction. The exercise protocol will last 60-90 seconds (a total of 60 knee extensions) followed by 6 minutes of rest. The intensity of the exercise decreases phosphocreatine (PCr) levels with minimal change in muscle pH. Spectra analysis was performed with AMARES from the jMRUI software package. Spectra are used to calculate the relative concentrations of inorganic phosphate (Pi), PCr, and ATP. PCr recovery will be measured through 6min of rest and fit with a monoexponential equation.
16 weeks
Insulin sensitivity (SI) by insulin clamp
Primary endpoint for the hyperinsulinemic euglycemic clamp testing will be insulin sensitivity defined as (glucose disposal rate - concentration of infused glucose)/(insulin concentration at steady state - fasting insulin concentration). Units are mg/min per microunit per milliliter.
16 weeks
total work performed on cycle ergometry VO2
Total work will be obtained by cycle ergometry using standard protocol measuring oxygen uptake starting at 0 watts (W) at 60 rotations per minute (rpm) increasing by 25W every 2 minutes until volitional exhaustion adapting a prior protocol used in CKD patients. The primary measure will be total work completed (Joules).
16 weeks
muscle work efficiency cycle ergometry
joules/ml Oxygen(VO2 peak)
16 weeks
Walking endurance by 6-minute walk
Meters
16 weeks
FACIT-F Fatigue (PRO)
score on FACIT-F questionnaire
16 weeks
Secondary Outcomes (3)
Intermuscular fat by MRI
16 weeks
30 second sit to stand test
16 weeks
PROMIS Fatigue (PRO)
16 weeks
Other Outcomes (2)
Muscle mitochondrial respiration from in situ high resolution respirometry of muscle biopsy tissue
16 weeks
Inflammatory cytokines. TNF-alpha and IL-6
16 weeks
Study Arms (2)
Sodium bicarbonate 16 weeks
EXPERIMENTALSodium bicarbonate will be dosed at 0.8meq per kilogram of ideal body weight daily (1meq is approximately 84mg). We will use the Devine formula to determine ideal body weight. Investigational Drug Services at both UC Davis and Vanderbilt will compound the sodium bicarbonate. Sodium bicarbonate 650 mg tablets will be over-encapsulated and matching placebo capsules will be prepared. Participants will be limited to a maximum of 9 capsules daily (maximum dose = 5850mg of sodium bicarbonate). Capsules will be dispensed to patients in two separate 8-week allotments. The dose will be rounded to the nearest whole capsule and depending on participant preference may be divided into portions taken twice or thrice daily. Given the high probability of interruption in sodium bicarbonate supply and availability, we may need to change brands of sodium bicarbonate intermittently.
placebo 16 weeks
PLACEBO COMPARATORMicrocrystalline cellulose
Interventions
Sodium bicarbonate will be dosed at 0.8meq per kilogram of ideal body weight daily (1meq is approximately 84mg). We will use the Devine formula to determine ideal body weight. Investigational Drug Services at both UC Davis and Vanderbilt will compound the sodium bicarbonate. Sodium bicarbonate 650 mg tablets will be over-encapsulated and matching placebo capsules will be prepared. Participants will be limited to a maximum of 9 capsules daily (maximum dose = 5850mg of sodium bicarbonate). Capsules will be dispensed to patients in two separate 8-week allotments. The dose will be rounded to the nearest whole capsule and depending on participant preference may be divided into portions taken twice or thrice daily. Given the high probability of interruption in sodium bicarbonate supply and availability, we may need to change brands of sodium bicarbonate intermittently.
The placebo and filler for for sodium bicarbonate capsules will be comprised of microcrystalline cellulose. Capsule appearance for control and sodium bicarbonate will be the same.
Eligibility Criteria
You may qualify if:
- Moderate-severe CKD determined by eGFR \<50ml/min per 1.73m2 by CKD EPI equation on at least 2 consecutive occasions.
- Metabolic acidosis defined as bicarbonate level\<24 on two consecutive occasions. Bicarbonate level of 24 or less allowed if eGFR\<=45ml/min per 1.73m2
- Age 21 to 85 years old
You may not qualify if:
- Type 1 diabetes
- Poorly controlled diabetes (HgbA1c\>10%)
- History of persistent hyperkalemia (K\>5.4)
- History of persistent hypokalemia (K\<3.3)
- Uncontrolled blood pressure (\>170/100)
- Chronic treatment with renal replacement therapy
- History of aortic dissection or severe valvular heart disease
- Exercise induced angina
- Uncontrolled cardiac dysrhythmia
- Oxygen dependent chronic obstructive pulmonary disease (COPD)
- Symptomatic claudication
- End stage liver disease
- Mobility disability defined as inability to walk without human assistance
- Dementia or psychosis
- Patients who cannot consent
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
University of California Davis Health
Sacramento, California, 95817, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Baback Roshanravan, MD
UC Davis
- PRINCIPAL INVESTIGATOR
Jorge Gamboa, MD PhD
Vanderbilt University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 8, 2021
First Posted
July 30, 2021
Study Start
September 8, 2023
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2026
Last Updated
May 6, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- within 18 months after the conclusion of the study. This data will be available indefinitely
Individual participant data will be available to other investigators on request. The requests will include a proposal outlining the research question, specific exposures, outcomes of interest and analytic plan. All requests will be reviewed by the study principal investigators and coinvestigators prior to release of data. All data will be de-identified.