Bone Loss, Chronic Kidney Diseases
Conditions
Keywords
Chronic Kidney Disease, Bone strength, Fractures, Pediatrics, Metabolic acidosis
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.
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.
Interventions
Oral potassium citrate extended-release tablet
OTHERPlacebo
Placebo capsule identical to active ingredient
DRUGPotassium Citrate and Citric Acid Oral Solution
Oral potassium citrate and citric acid
Sponsors
Albert Einstein College of Medicine
Columbia University
University of Pittsburgh Medical Center
University of Utah
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NYU Langone Health
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
(Pediatric Inclusion): * Children 5-17 years old * Estimated glomerular filtration rate (eGFR) ≥ 30 and \<90 ml/min/1.73m2 by Chronic Kidney Disease in Children (CKiD) Under 25 (U25) GFR estimating equations * Females of child-bearing potential must have had a menstrual period in the last month * Levels of parathyroid hormone (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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Volumetric Bone Mineral Density (BMD) - Distal Radius | Baseline to 6 months | 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. |
| Change in Total Volumetric Bone Mineral Density (BMD) - Tibia | Baseline to 6 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in 24-hour Urine Net Acid Excretion (NAE) | Baseline to 6 months | 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). |
| Change in Parathyroid Hormone (PTH) Levels | Baseline to 6 months | 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. |
| Change in Circulating Biomarkers of Bone Resorption | Baseline to 6 months | 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. |
| Change in Circulating Biomarkers of Bone Formation | Baseline to 6 months | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKimberly Reidy, MD
Albert Einstein College of Medicine
Participant flow
Pre-assignment details
Seven (7) patients were consented and six (6) of these patients were formally enrolled into the study following completion of the screening visit (Visit 1). Four (4) of the six (6) patients completed Visit 2 and were eligible to start the Run-in Period (Visit 3). Two participants completed Visit 3; however, the study was terminated as one of the patients was in the washout period. Only one (1) patient was randomized into the study (placebo arm) at the time of study termination.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 16 years STANDARD_DEVIATION 0 |
| Chronic Kidney Disease (CKD) Etiology - Adult Participants Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) | 0 Participants |
| Chronic Kidney Disease (CKD) Etiology - Adult Participants Diabetic Nephropathy | 0 Participants |
| Chronic Kidney Disease (CKD) Etiology - Adult Participants Glomerular | 0 Participants |
| Chronic Kidney Disease (CKD) Etiology - Adult Participants Glomerulonephritis/Nephrosis | 0 Participants |
| Chronic Kidney Disease (CKD) Etiology - Adult Participants Hypertensive Nephropathy | 0 Participants |
| Chronic Kidney Disease (CKD) Etiology - Adult Participants Other (Unspecified) | 2 Participants |
| Chronic Kidney Disease (CKD) Etiology - Adult Participants Tubulointerstitial | 0 Participants |
| Chronic Kidney Disease (CKD) Etiology - Pediatric Participants Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) | 0 Participants |
| Chronic Kidney Disease (CKD) Etiology - Pediatric Participants Diabetic Nephropathy | 0 Participants |
| Chronic Kidney Disease (CKD) Etiology - Pediatric Participants Glomerular | 0 Participants |
| Chronic Kidney Disease (CKD) Etiology - Pediatric Participants Glomerulonephritis/ Nephrosis | 0 Participants |
| Chronic Kidney Disease (CKD) Etiology - Pediatric Participants Hypertensive Nephropathy | 0 Participants |
| Chronic Kidney Disease (CKD) Etiology - Pediatric Participants Other (Unspecified) | 0 Participants |
| Chronic Kidney Disease (CKD) Etiology - Pediatric Participants Tubulointerstitial | 0 Participants |
| CKD Stage - Adult Participants CKD stage 1 | 0 Participants |
| CKD Stage - Adult Participants CKD stage 2 | 1 Participants |
| CKD Stage - Adult Participants CKD stage 3a | 0 Participants |
| CKD Stage - Adult Participants CKD stage 3b | 0 Participants |
| CKD Stage - Adult Participants CKD stage 4 | 0 Participants |
| CKD Stage - Adult Participants CKD stage 5 | 0 Participants |
| CKD Stage - Pediatric Participants CKD stage 1 | 0 Participants |
| CKD Stage - Pediatric Participants CKD stage 2 | 1 Participants |
| CKD Stage - Pediatric Participants CKD stage 3a | 0 Participants |
| CKD Stage - Pediatric Participants CKD stage 3b | 0 Participants |
| CKD Stage - Pediatric Participants CKD stage 4 | 0 Participants |
| CKD Stage - Pediatric Participants CKD stage 5 | 0 Participants |
| Ethnicity - Adult Participants Hispanic | 0 Participants |
| Ethnicity - Adult Participants Not Hispanic | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Ethnicity - Pediatric Participants Hispanic | 0 Participants |
| Ethnicity - Pediatric Participants Not Hispanic | 1 Participants |
| Race - Adult Participants American Indian/Alaska Native | 0 Participants |
| Race - Adult Participants Asian | 0 Participants |
| Race - Adult Participants Black or African American | 0 Participants |
| Race - Adult Participants Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race - Adult Participants Other | 0 Participants |
| Race - Adult Participants Unknown or not reported | 0 Participants |
| Race - Adult Participants White | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Race - Pediatric Participants American Indian/Alaska Native | 0 Participants |
| Race - Pediatric Participants Asian | 0 Participants |
| Race - Pediatric Participants Black or African American | 0 Participants |
| Race - Pediatric Participants Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race - Pediatric Participants Other | 0 Participants |
| Race - Pediatric Participants Unknown or not reported | 0 Participants |
| Race - Pediatric Participants White | 0 Participants |
| Region of Enrollment United States | 6 participants |
| Sex - Adult Participants Female | 0 Participants |
| Sex - Adult Participants Male | 0 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
| Sex - Pediatric Participants Female | 0 Participants |
| Sex - Pediatric Participants Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 1 | 0 / 4 |
| other Total, other adverse events | 0 / 0 | 1 / 1 | 1 / 4 |
| serious Total, serious adverse events | 0 / 0 | 0 / 1 | 0 / 4 |
Outcome results
None listed