for people ages 30-85 (full criteria)
study started
estimated completion
Principal Investigator
by Baback Roshanravan, MD (ucdavis)



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.

Official Title

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


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 power repeated muscle contraction. Investigators showed metabolic acidosis and muscle adiposity as the major determinants of muscle mitochondrial function. Metabolic acidosis (MA) is long believed to be the main mechanism leading to skeletal muscle wasting and peripheral insulin resistance in CKD. Skeletal muscle mitochondrial metabolism is considered a principal determinant of peripheral insulin sensitivity and muscle quality, but little is known of the impact of MA on muscle mitochondrial function. Muscle mitochondrial dysfunction leads to defective lipid metabolism augmenting adiposity and lipotoxic intermediates resulting in insulin resistance, low endurance, and muscle atrophy. Using in vivo 31Phosphorus Magnetic Resonance Spectroscopy (31P MRS) investigators showed that the presence and severity of CKD is strongly associated with impaired muscle mitochondrial capacity to generate ATP translating into poor walking endurance. Investigators also showed MA and muscle adiposity are the major determinants of muscle mitochondrial function. Recently a non-sodium polymer (veverimer) selectively binding hydrogen chloride in gastrointestinal tract safely improved serum bicarbonate and meaningfully improved physical functioning in a randomized clinical trial. Despite the importance of mitochondrial function to muscle health, it is unknown if treatment of MA benefits muscle mitochondrial function, adiposity or endurance in CKD. The proposed project will use precise, in vivo 31P MRS and gold-standard testing of peripheral insulin sensitivity by hyperinsulinemic euglycemic clamp to probe the pathophysiology of MA and low endurance in a clinical trial of alkali therapy in CKD and MA. We will compare veverimer or low-dose sodium bicarbonate to placebo in a multicenter randomized, double-dummy placebo-controlled, cross-over trial design in 102 persons with moderate-severe CKD and MA. First, the efficacy of 3-months of alkali therapy will be tested comparing veverimer or low dose sodium bicarbonate versus placebo on muscle metabolic health in a randomized crossover trial in MA. Second, Test the efficacy of 3-months of alkali therapy comparing veverimer or low dose sodium bicarbonate versus placebo on improving physical endurance in MA. The rationale is that identification of therapeutic targets for low physical endurance will inform the development of pharmacologic interventions. Long term, it is expected that strategies treating MA will improve exercise tolerance enabling effective engagement in lifestyle interventions improving quality of life in CKD.


Chronic Kidney Diseases Metabolic Acidosis Fatigue Physical Endurance Insulin Resistance Mitochondrial Energetics Diabetes Chronic kidney disease Kidney Diseases Renal Insufficiency, Chronic Acidosis Veverimer Sodium bicarbonate


You can join if…

Open to people ages 30-85

  • Moderate-severe CKD determined by eGFR <60ml/min per 1.73m2 by CKD EPI equation on at least 2 consecutive occasions.
  • Metabolic acidosis defined as bicarbonate level<23 on two consecutive occasions.
  • Age 30 to 85 years old

You CAN'T join if...

  • Type 2 diabetes managed with insulin treatment
  • Poorly controlled diabetes (HgbA1c>10%)
  • History of persistent hyperkalemia (K>5.4)
  • Chronic treatment with renal replacement therapy
  • History of aortic dissection or severe valvular heart disease
  • Exercise induced angina
  • Uncontrolled cardiac dysrhythmia
  • Oxygen dependent 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 IV 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.
  • Any condition which in the judgement of the clinical investigator places the participant at risk from participation in the study.

Lead Scientist at University of California Health

  • Baback Roshanravan, MD (ucdavis)
    Associate Professor, Nephrology. Authored (or co-authored) 31 research publications


not yet accepting patients
Start Date
Completion Date
University of California, Davis
Phase 2 Research Study
Study Type
Expecting 102 study participants
Last Updated