Bone in CKD Alkali Response (BICARb Pilot Trial)

ConditionsChronic Kidney Diseases Bone Loss

Trial statusRecruiting

Trial phasePhase 2, Phase 3

Trial typeInterventional

Biological sexAll

Age5-100

SponsorAlbert Einstein College of Medicine

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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)

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

Potassium Citrate Extended Release Oral Tablet
Drug
Oral potassium citrate extended-release tablet
Placebo
Other intervention
Placebo capsule identical to active ingredient
Potassium Citrate and Citric Acid Oral Solution
Drug
Oral potassium citrate and citric acid

Treatment groups

103 Participants

are divided into 2 treatment groups

Group A: Potassium CitrateExperimental treatment 2 interventions

Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame

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.

Time frame

Baseline to 6 months

Secondary outcomes

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

Change in 24-hour urinary NAE from baseline will be assessed by analyzing samples obtained from 24-hour timed urine collections using laboratory titration methods. Results will be quantified and summarized by study arm using basic descriptive statistics and subsequently analyzed for between group treatment changes. Standard urinary NAE values vary but can range from 250-750 mg/24 hours (1.48 to 4.43 mmol/24 hours).

Time frame

Baseline to 6 months

Change in Parathyroid Hormone (PTH) levels

Change in circulating PTH concentration from baseline will be assessed by the collection of blood samples via venipuncture and analysis for circulating PTH by an immunoassay. Results will be summarized by study arm using basic descriptive statistics and subsequently statistically analyzed for between group changes. Standard PTH reference ranges can vary but are generally between 10-65 pg/mL in plasma.

Time frame

Baseline to 6 months

Change in circulating biomarkers of bone resorption

Change in circulating biomarkers of bone resorption from baseline will be assessed following the collection of blood samples via venipuncture and subsequent analysis for circulating C-terminal telopeptides of type I collagen using a cross-linking telopeptide of type I collagen (CTX blood test) assay. C-terminal telopeptides can be used as a biomarker to measure bone resorption and turnover. Elevated levels of C-terminal telopeptide can be indicative of increased bone resorption. While standard reference ranges for C-terminal telopeptide can vary, for premenopausal women ranges are typically 40-465 pg/mL in serum and 19-83 ug/L in plasma.

Time frame

Baseline to 6 months

Change in circulating biomarkers of bone formation

Change in circulating biomarker of bone formation from baseline will be assessed following the collection of blood samples via venipuncture and subsequent analysis for procollagen type-1 N-terminal propeptide (P1NP). A P1NP assay measures the amount of amino-terminal propeptide of type I procollagen in the serum and can be used as biomarker to measure the rate of bone formation. While reference ranges can vary by age, standard reference ranges in adult premenopausal women are 19-83 ug/L.

Time frame

Baseline to 6 months

Other outcomes

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.

Time frame

6 months

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.

Time frame

6 months

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.

Time frame

6 months

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.

Time frame

6 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Albert Einstein College of Medicine

Lead sponsor

Columbia University

Collaborator

University of Pittsburgh Medical Center

Collaborator

University of Utah

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Source ClinicalTrials.gov

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