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.
* 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.
Brief Title
Bone in CKD Alkali Response (BICARb Pilot Trial)
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.
Central Contacts
Central Contact Role
Contact
Central Contact Phone
718-655-1120
Central Contact Email
kreidy@montefiore.org
Completion Date
Completion Date Type
Estimated
Conditions
Chronic Kidney Diseases
Bone Loss
Eligibility 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
* 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
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
* 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
Gender
All
Gender Based
false
Keywords
Chronic Kidney Disease
Bone strength
Fractures
Pediatrics
Metabolic acidosis
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
100 Years
Minimum Age
5 Years
NCT Id
NCT05918029
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2023-14826
Overall Status
Recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Bone in CKD Alkali Response Pilot Trial (BICARb)
Primary Outcomes
Outcome Description
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.
Outcome Measure
Change in Total volumetric bone mineral density (BMD) - Distal Radius
Outcome Time Frame
Baseline to 6 months
Outcome Description
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.
Outcome Measure
Change in Total volumetric bone mineral density (BMD) - Tibia
Outcome Time Frame
Baseline to 6 months
Secondary Ids
Secondary Id
R01DK131811
Secondary Outcomes
Outcome Description
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).
Outcome Time Frame
Baseline to 6 months
Outcome Measure
Change in 24-hour Urine Net Acid Excretion (NAE)
Outcome Description
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.
Outcome Time Frame
Baseline to 6 months
Outcome Measure
Change in Parathyroid Hormone (PTH) levels
Outcome Description
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.
Outcome Time Frame
Baseline to 6 months
Outcome Measure
Change in circulating biomarkers of bone resorption
Outcome Description
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.
Outcome Time Frame
Baseline to 6 months
Outcome Measure
Change in circulating biomarkers of bone formation
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
100
Minimum Age Number (converted to Years and rounded down)
5
Investigators
Investigator Type
Principal Investigator
Investigator Name
Kimberly Reidy
Investigator Email
kreidy@montefiore.org
Investigator Phone
718-655-1120