Bone in CKD Alkali Response (BICARb Pilot Trial)

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified September 2024 by Albert Einstein College of Medicine
Sponsor
Albert Einstein College of Medicine
Information Provided by (Responsible Party)
Albert Einstein College of Medicine
Clinicaltrials.gov Identifier
NCT05918029
Other Study ID Numbers:
2023-14826
First Submitted
June 1, 2023
First Posted
June 25, 2023
Last Update Posted
October 14, 2024
Last Verified
September 2024

ClinicalTrials.gov processed this data on October 2024. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

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.

Condition or DiseaseIntervention/Treatment
Chronic Kidney DiseasesBone Loss
Drug: Potassium Citrate Extended Release Oral TabletOther: Placebo

Study Design

Study TypeInterventional
Actual Enrollment103 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleBone in CKD Alkali Response Pilot Trial (BICARb)
Study Start DateAugust 14, 2024
Actual Primary Completion Date3mos 1w from now
Actual Study Completion Date3mos 1w from now

Groups and Cohorts

Group/CohortIntervention/Treatment
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. 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
Oral potassium citrate extended-release tablet
Placebo
Placebo capsules identical to the active capsules.
Other: Placebo
Placebo capsule identical to active ingredient

Outcome Measures

Primary Outcome Measures
  1. 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.
  2. 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.
Secondary Outcome Measures
  1. 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).
  2. 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.
  3. 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.
  4. 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.

Eligibility Criteria

Ages Eligible for Study(Child, Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Inclusion Criteria (Pediatric Inclusion):
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)
25-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) Inclusion Criteria (Adult Inclusion):
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
Exclusion Criteria
Inclusion Criteria (Pediatric Inclusion):
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)
25-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) Inclusion Criteria (Adult Inclusion):
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 Exclusion Criteria (Pediatric and Adult):
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
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

Contacts and Locations

Sponsors and CollaboratorsAlbert Einstein College of Medicine
Locations
Albert Einstein College of Medicine | The Bronx New York, United States, 10461University of Pittsburgh Medical Center | Pittsburgh Pennsylvania, United States, 15213
Investigators
Principal Investigator: Kimberly Reidy, MD, Albert Einstein College of Medicine