Bone in CKD Alkali Response (BICARb Pilot Trial)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Bone in CKD Alkali Response Pilot Trial (BICARb)

Conditions
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Chronic Kidney Diseases, Bone Loss

Intervention / Treatment
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* Drug: Potassium citrate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Potassium Citrate<br>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<br>* Oral potassium citrate<br>|
| Placebo Comparator: Placebo<br>Placebo capsules identical to the active capsules. | Drug: Placebo<br>* Placebo capsule identical to active ingredient<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 24 hour net Urine Acid Excretion (NAE) | Change of urine acid excretion in 24-hour net Urine Acid Excretion (NAE) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in parathyroid hormone | Change from baseline to 6 months in median parathyroid hormone levels | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Kidney Disease, Bone strength, Fractures, Pediatrics, Metabolic acidosis