Bone in CKD Alkali Response (BICARb Pilot Trial)

Chronic Kidney Diseases Clinical Trial

— BICARb  

Official title:

Bone in CKD Alkali Response Pilot Trial (BICARb)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05918029
• Other study ID #: 2023-14826
• Secondary ID: R01DK131811
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: June 2024
• Est. completion date: June 2026

Study information

• Verified date: May 2024
• Source: Albert Einstein College of Medicine
• Contact: Kimberly Reidy, MD
• Phone: 718-741-2450
• Email: kreidy[@]montefiore.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to test whether potassium citrate improves skeletal health in adults and children with chronic kidney disease. The main questions it aims to answer are:

• To evaluate effects of potassium citrate treatment on bone quality and strength.

• To evaluate mechanism(s) underlying the effects of potassium citrate on skeletal health.

Participants will be asked to:

• provide blood, urine and answer questions about health and diet three times during an 8 months period

• undergo advanced bone imaging with high resolution-peripheral quantitative CT scan twice during 8 months

• take study pills for 4-6 weeks at the beginning of the study to ensure safety

• take either potassium citrate or placebo for 6 months during the blinded portion of the study

Researchers will compare the bone imaging between the potassium citrate and the placebo groups at the end of the study.

Description:

Chronic kidney disease is associated with bone loss and fractures in both children and adults, but bone protective therapies that are both proven and safe to use across the life-course in CKD are lacking. In this study, the investigators will conduct a pilot, double-blinded, randomized, placebo-controlled trial in 15 children and 88 adults evaluating the skeletal effects of potassium alkali therapy. These data will form the basis for a larger U01 proposal to determine the efficacy of potassium citrate on mitigating the effects of CKD on bone.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 103
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 100 Years

Eligibility

Inclusion Criteria:

• Age = 5 years old

• For children: Estimated eGFR >30 and <90 ml/min/1.73m2 by CKiD U25 (For Pediatric participants) equations

• For adults (=18 years old): Estimated eGFR >30 and <90 ml/min/1.73m2 by the new CKD-Epi without race (For Adults)

• Females of child-bearing potential must have had a menstrual period in the last month

• For participants < 18 years, the participant and/or parent/guardian capable of providing informed consent and assent (assessed by the provider)

• Proficiency in English or Spanish

• PTH and phosphorus levels within the normal range

• 25-hydroxyvitamin D = 20 ng/mL

• Women of childbearing potential must be willing to use one form of effective contraception over the course of the study

Exclusion Criteria:

• Baseline potassium > or = 5.5 mEq/L or prior history of hyperkalemia in the last 6 months (potassium >5.5 mEq/L) or currently taking a potassium lowering agent

• Alkali therapy within the prior 12 months

• Baseline ECG with abnormalities associated with increased risk of arrythmia, excluding left ventricular hypertrophy

• Baseline serum bicarbonate levels <17 or > or = 30 mEq/L

• Serum calcium <8.6 mg/dL, adjusted for serum albumin

• Significant comorbidity causing acid-base imbalance (e.g. active cancer requiring chemotherapy, chronic liver failure, moderate or severe chronic obstructive lung disease, New York Heart Association class 2 or greater congestive heart failure, obstructive sleep apnea requiring nightly continuous positive airway pressure, active glomerular disease requiring immunosuppressive therapy, intestinal malabsorption or celiac disease)

• Plans to relocate out of the area in the next 3 months

• Urine pH > 8 or history of nephrolithiasis

• Lower extremity amputations or non-ambulatory

• Metabolic bone disease not related to CKD (e.g., Paget's disease, primary hyperparathyroidism)

• Endocrinopathy: untreated hyper or hypothyroidism, Cushing's syndrome

• Medical diseases that can affect therapy (severe myocardial damage, acute dehydration, delayed gastric emptying, esophageal compression, or intestinal obstruction or stricture)

• Use of bisphosphonates, denosumab, teriparatide, abaloparatide, romosozumab, raloxifene, estrogen or testosterone replacement therapy, glucocorticoids within the 12-months prior to enrollment

• Previous bilateral wrist and tibia fractures

• Solid or liquid organ transplant

• On dialysis or with rapidly deteriorating kidney function or expectation for transplantation or initiation of dialysis in less than 3 months

• Pregnancy or breastfeeding

• Prisoners or institutionalized individuals

• Unwillingness to provide informed consent

Related Conditions & MeSH terms

• Bone Loss
• Chronic Kidney Diseases
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Potassium citrate
Oral potassium citrate
• Placebo
Placebo capsule identical to active ingredient

Locations

Country	Name	City	State
United States	Albert Einstein College of Medicine	Bronx	New York
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania

Sponsors (5)

Lead Sponsor	Collaborator
Albert Einstein College of Medicine	Columbia University, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Pittsburgh Medical Center, University of Utah

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Correlation of serum bicarbonate and urine NAE	Correlation coefficient will be determined between serum bicarbonate and urine net acid excretion. The correlation coefficient is a number between 0 and 1, with 0 being no correlation and 1 being perfect correlation.	6 months
Other	Correlation of serum bicarbonate and bone quality	Correlation coefficient will be determined between serum bicarbonate and bone quality. The correlation coefficient is a number between 0 and 1, with 0 being no correlation and 1 being perfect correlation.	6 months
Other	Correlation between urine net acid excretion and bone quality	Correlation coefficient will be determined between urine net acid excretion and bone quality. The correlation coefficient is a number between 0 and 1, with 0 being no correlation and 1 being perfect correlation.	6 months
Other	Changes in bone alkaline phosphatase	Changes in bone alkaline phosphatase will be compared between the groups. Bone alkaline phosphatase is measured in IU/L. Higher values are indicative of higher bone turnover.	6 months
Other	Changes in TRAP5b	Changes in TRAP5b compared between the groups. TRAP5b are measured in mIU/mL.	6 months
Other	Changes in bone quality	Bone quality as measured by high resolution peripheral quantitative CT will be compared between groups	6 months
Primary	Total volumetric bone mineral density (BMD)	Change in total volumetric bone mineral density (BMD) by high resolution peripheral quantitative computed tomography (HR-pQCT).	6 months
Primary	24 hour net Urine Acid Excretion (NAE)	Change of urine acid excretion in 24-hour net Urine Acid Excretion (NAE)	6 months
Secondary	Changes in parathyroid hormone	Change from baseline to 6 months in median parathyroid hormone levels	6 months