Bone in CKD Alkali Response (BICARb Pilot Trial)

NCT05918029 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2023-14826R01DK131811
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 2

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 As part of the study, there will be a run-in period followed by the placebo-controlled randomized clinical trial. Researchers will compare the bone imaging between the potassium citrate and the placebo groups at the end of the study.

Conditions

Chronic Kidney Diseases; Bone Loss

Keywords

Chronic Kidney Disease; Bone strength; Fractures; Pediatrics; Metabolic acidosis

Outcome Measures

Primary Outcomes (2)

• Change in Total volumetric bone mineral density (BMD) - Distal Radius

  Change in total volumetric BMD will be analyzed by high resolution peripheral quantitative computed tomography (HR-pQCT). The 6-month absolute and relative (percent) changes in Z-score in distal radius total volumetric BMD will summarized by study arm and analyzed for between group treatment changes.

  Baseline to 6 months

• Change in Total volumetric bone mineral density (BMD) - Tibia

  Change in total volumetric BMD will be analyzed by high resolution peripheral quantitative computed tomography (HR-pQCT). The 6-month absolute and relative (percent) changes in Z-score in tibia total volumetric BMD will summarized by study arm and analyzed for between group treatment changes.

  Baseline to 6 months

Secondary Outcomes (4)

• Change in 24-hour Urine Net Acid Excretion (NAE)

  Baseline to 6 months

• Change in Parathyroid Hormone (PTH) levels

  Baseline to 6 months

• Change in circulating biomarkers of bone resorption

  Baseline to 6 months

• Change in circulating biomarkers of bone formation

  Baseline to 6 months

Other Outcomes (6)

• Correlation of serum bicarbonate and urine NAE

  6 months

• Correlation of serum bicarbonate and bone quality

  6 months

• Correlation between urine net acid excretion and bone quality

  6 months

Study Arms (2)

Potassium Citrate

EXPERIMENTAL

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. OR (for children who cannot take pills): Potassium citrate and citric acid for oral solution 1 mEq/kg/day divided into two doses to a maximum dose of 30 mEq twice daily

Drug: Potassium Citrate Extended Release Oral Tablet; Drug: Potassium Citrate and Citric Acid Oral Solution

Placebo

PLACEBO COMPARATOR

Placebo capsules identical to the active capsules.

Other: Placebo

Interventions

Potassium Citrate Extended Release Oral Tablet DRUG

Oral potassium citrate extended-release tablet

Potassium Citrate

Placebo OTHER

Placebo capsule identical to active ingredient

Placebo

Potassium Citrate and Citric Acid Oral Solution DRUG

Oral potassium citrate and citric acid

Potassium Citrate

Eligibility Criteria

• Age: 5 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Children 5-17 years old
• Estimated eGFR \>30 and \<90 ml/min/1.73m2 by CKiD U25 equations
• Females of child-bearing potential must have had a menstrual period in the last month
• Levels of PTH and alkaline phosphatase within 2x normal range and phosphorus within the normal range for age (per local laboratory reference assay)
• hydroxy Vitamin D ≥ 20 ng/mL
• Females of child-bearing potential must be willing to use one form of effective contraception over the course of the study
• Proficiency in English or Spanish
• For participants \< 18 years, the participant and/or parent/guardian capable of providing informed consent and assent (assessed by the provider)
• Adults ≥ 18 years old
• Estimated eGFR \>30 and \<90 ml/min/1.73m2 by the new CKD-Epi without race
• Pre-menopausal women of childbearing age must have had a menstrual period in the last month
• Levels of PTH and alkaline phosphatase within 2x normal range and phosphorus up to 5.0 mg/dL (per local laboratory reference assay)
• Levels of 25-hydroxy Vitamin D ≥ 20 ng/mL
• Women of childbearing potential must be willing to use one form of effective contraception over the course of the study
• Proficiency in English or Spanish

You may not qualify if:

• Baseline potassium ≥ 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 ≥ 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, or an unstable dose of glucocorticoids within the 12-months prior to enrollment
• Previous bilateral wrist and tibia fractures
• Solid or liquid organ transplant

Sponsors & Collaborators

• Albert Einstein College of Medicine: lead
• Columbia University: collaborator
• University of Pittsburgh Medical Center: collaborator
• University of Utah: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Related Publications (1)

• Kilduff S, Brown DD, Melamed ML. Treating Metabolic Acidosis for CKD Progression? Need for Higher Quality Data. Clin J Am Soc Nephrol. 2025 Jan 1;20(1):147-149. doi: 10.2215/CJN.0000000632. Epub 2024 Nov 20. No abstract available.

  PMID: 39665575 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Bone Diseases, Metabolic; Fractures, Bone; Acidosis

Interventions

Potassium Citrate; Citric Acid

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Wounds and Injuries; Acid-Base Imbalance

Intervention Hierarchy (Ancestors)

Citrates; Tricarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Kimberly Reidy, MD

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kimberly Reidy, MD

CONTACT

718-655-1120; kreidy@montefiore.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2023
• First Posted: June 26, 2023
• Study Start: August 15, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)