Bone in CKD Alkali Response (BICARb Pilot Trial)

Sponsor

Albert Einstein College of Medicine (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05918029

Collaborator

Columbia University (Other), University of Pittsburgh Medical Center (Other), University of Utah (Other)

103

Enrollment

Location

Arms

26.1

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Diseases Bone Loss	Drug: Potassium citrate Drug: Placebo	Phase 2/Phase 3

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

103 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Bone in CKD Alkali Response Pilot Trial (BICARb)

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Potassium Citrate Potassium Citrate extended-release tablets 30 mEq twice daily (1 mEq/kg/day divided into two doses for children to a maximum dose of 30 mEq twice daily).	Drug: Potassium citrate Oral potassium citrate
Placebo Comparator: Placebo Placebo capsules identical to the active capsules.	Drug: Placebo Placebo capsule identical to active ingredient

Arm

Intervention/Treatment

Experimental: Potassium Citrate

Potassium Citrate extended-release tablets 30 mEq twice daily (1 mEq/kg/day divided into two doses for children to a maximum dose of 30 mEq twice daily).

Drug: Potassium citrate

Oral potassium citrate

Placebo Comparator: Placebo

Placebo capsules identical to the active capsules.

Drug: Placebo

Placebo capsule identical to active ingredient

Outcome Measures

Primary Outcome Measures

Total volumetric bone mineral density (BMD) [6 months]
Change in total volumetric bone mineral density (BMD) by high resolution peripheral quantitative computed tomography (HR-pQCT).
24 hour net Urine Acid Excretion (NAE) [6 months]
Change of urine acid excretion in 24-hour net Urine Acid Excretion (NAE)

Secondary Outcome Measures

Changes in parathyroid hormone [6 months]
Change from baseline to 6 months in median parathyroid hormone levels

Other Outcome Measures

Correlation of serum bicarbonate and urine NAE [6 months]
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.
Correlation of serum bicarbonate and bone quality [6 months]
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.
Correlation between urine net acid excretion and bone quality [6 months]
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.
Changes in bone alkaline phosphatase [6 months]
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.
Changes in TRAP5b [6 months]
Changes in TRAP5b compared between the groups. TRAP5b are measured in mIU/mL.
Changes in bone quality [6 months]
Bone quality as measured by high resolution peripheral quantitative CT will be compared between groups

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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