Randomized Cross-over Trial of Sodium Bicarbonate on Muscle Mitochondrial Energetics and Physical Endurance in Chronic Kidney Disease and Metabolic Acidosis
University of California, Davis
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.
Description
Chronic kidney disease (CKD) is highly prevalent affecting 14% of the U.S. population leading to substantial morbidity and reduced quality of life. Older adults with CKD identify maintenance of functional independence as their top priority. Skeletal muscle health is critical for mobility and an underrecognized target of metabolic acidosis (MA) and protein energy wasting in CKD. Skeletal muscle endurance provides a window into muscle metabolic health and muscle quality. Muscle mitochondrial metabolism is central to muscle and walking endurance providing energy from carbohydrates and fats to pow…
Eligibility
- Age range
- 21–85 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 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 Exclusion Criteria: * 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…
Interventions
- DrugSodium bicarbonate
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.
- Drugplacebo
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.
Locations (2)
- University of California Davis HealthSacramento, California
- Vanderbilt University Medical CenterNashville, Tennessee