RecruitingPhase 2NCT04984226

Sodium Bicarbonate and Mitochondrial Energetics in Persons With CKD

Randomized Cross-over Trial of Sodium Bicarbonate on Muscle Mitochondrial Energetics and Physical Endurance in Chronic Kidney Disease and Metabolic Acidosis

Sponsor

University of California, Davis

Enrollment

80 participants

Start Date

Sep 8, 2023

Study Type

INTERVENTIONAL

Conditions

Insulin Resistance Chronic Kidney Diseases Fatigue Diabetes Metabolic Acidosis Physical Endurance Mitochondrial Energetics

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.

Eligibility

Min Age: 21 YearsMax Age: 85 Years

Inclusion Criteria3

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 Criteria28

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
Active use of intraveneous drugs
Non-english speaking
History of transplant
Implants that prohibit MRI measurements or trauma involving metal fragments
Pacemaker
Expectation to start dialysis during the course of study.
Women who are breastfeeding, pregnant, or are wanting to become pregnant
Any condition which in the judgement of the clinical investigator places the participant at risk from participation in the study.
Drugs- anticoagulants or antiplatelets:
Anticoagulants, any 1 (coumadin, rivaroxaban, apixaban, dabigatran, edoxaban)
Antiplatelets, any 2 (aspirin, cilostazol, clopidogrel, dipyridamole, prasugrel, ticragrelor, ticlopidine, vorapaxar)
Platelet count \<100,000
International normalized ratio (INR)\>1.4

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.