Clinical trial NCT06712719: Effects of Dietary Phosphorus on Phosphorus and Calcium Whole-Body Balance and Kinetics in Moderate CKD
Official title: Effects of Dietary Phosphorus on Phosphorus and Calcium Whole-Body Balance and Kinetics in Moderate CKD
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: CKD
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2024-12-02
Enrollment: 22
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of the study is to look at the effects of dietary phosphorous on phosphorous and calcium whole-body balance and kinetics in moderate chronic kidney disease (CKD). N = 22 enrolled subjects will be randomly assigned to a cross-over order of (A) Low P Diet, High P Diet. Each cross-over phase will be 21 days and consist of a 7-day outpatient, controlled diet period, followed by a 7- day inpatient, controlled diet, balance, and kinetic study period, followed by a second 7-day outpatient, controlled diet period.

Detailed description: Chronic kidney disease (CKD) affects approximately 37 million (1 in 7) U.S. adults, most of whom experience mineral and bone disorders (CKD-MBD) that increase risk for cardiovascular events, bone fractures, and death. Dietary and pharmaceutical treatments for CKD-MBD have diverse effects on serum calcium and phosphorus levels, but their effects on the underlying physiological processes of calcium and phosphorus balance are largely unknown. This study aims to determine the effects of a low versus high phosphorus bioaccessibility diet on whole-body calcium and phosphorus balance and kinetics, including measures such as estimated intestinal absorption. This study will be a randomized two-phase cross-over design trial that will include a controlled study diet, calcium and phosphorus isotopes as tracers for kinetic modeling, stool and urine collections, and blood draws. After screening, eligible participants who choose to enroll in the study will be asked to participate in two cross-over sessions, each of three weeks duration during which time all food will be provided according to the randomized diet intervention assignment. After the first week on the study diet, participants will be asked to stay at the clinical research center when they will be given oral and intravenous doses of calcium and phosphorus isotopes. Serial blood draws and complete urine and fecal collections will be made for 1 week, then the final week will only include blood draws. Between cross-over sessions, there will be a washout period of 1-3 weeks. Participants will then switch diets and repeat the same study process as the first session. Calcium and phosphorus whole-body balance, intestinal absorption, renal excretion, and movement to and from bone will be determined for both minerals. This project will provide foundational knowledge of calcium and phosphorus physiology in CKD that will support progress towards preventing morbidity and mortality associated with CKD-MBD.

Eligibility criteria: Inclusion Criteria:

* Men or women, ages 30-75 years old, any race or ethnicity
* Moderate CKD, defined by KDIGO as eGFR category 3b (30-44 mL/min) or 4 (16-29 mL/min) with albuminuria categories A1-A3
* Serum intact parathyroid hormone above assay normal limit
* Female subjects must be postmenopausal (\>12 months since last menstrual period), surgically sterile, or confirmed not pregnant by pregnancy test
* Must be on stable doses of medications (except those noted in exclusion criteria) for at least 4 weeks prior to the study
* Willing to discontinue supplements (e.g., vitamin D, calcium, multivitamin/minerals, or others) upon enrollment until completion of the study
* Adequate vitamin D status defined as serum 25D \> 20 ng/mL based on National Academy of Medicine (then Institute of Medicine) criteria.

Exclusion Criteria:

* Plans to initiate dialysis within 6 months
* Hypercalcemia defined as corrected serum calcium \>9.8 mg/dL within past 3 months
* Hyperkalemia defined as serum potassium \>5.5 mg/dL within past 3 months
* Hyperphosphatemia defined as serum phosphate \>5.5 mg/dL within past 3 months
* Intestinal disease that alters absorption or normal intestinal function including celiac disease, small bowel resection, bariatric surgery, or chronic diarrhea/malabsorption
* Serious, uncontrolled underlying systemic disease including diabetes, lupus, hypertension in the opinion of their physician
* Pregnant or breastfeeding
* Prescribed and taken a phosphate binder medication, calcitriol, vitamin D analogs, calcimimetics, PTH analogues, and other medications that may alter Ca and P metabolism within past 4 weeks
* Non-English speaking

Primary outcomes:
measure: Phosphorus Balance
timeFrame: 1 week
measure: Calcium Balance
timeFrame: 1 week
Secondary outcomes:
measure: Fractional phosphorus absorption
timeFrame: 2 weeks
measure: Fractional calcium absorption
timeFrame: 2 weeks
measure: Bone phosphorus balance
timeFrame: 2 weeks
measure: Bone calcium balance
timeFrame: 2 weeks
measure: Urine phosphorus
timeFrame: 1 week
measure: Urine calcium
timeFrame: 1 week
measure: Net phosphorus absorption
timeFrame: 1 week
measure: Net calcium absorption
timeFrame: 1 week
measure: Creatinine clearance
timeFrame: 2hours, day 8
measure: Serum Fibroblast growth factor-23
timeFrame: Day1, Day8
measure: Serum Parathyroid hormone
timeFrame: Day1, Day8
measure: Serum 1,25-dihydroxyvitamin D
timeFrame: Day1, Day8
measure: Serum phosphate
timeFrame: Day1, Day8
measure: Serum calcium
timeFrame: Day1, Day8
Other outcomes:
Locations:
Study officials:
affiliation: University of Minnesota
name: Kathleen Hill Gallant, PhD
role: PRINCIPAL_INVESTIGATOR
References: