Calcium and Phosphorus Whole-Body Balance and Kinetics in Patients With Moderate Chronic Kidney Disease

This pilot study aims to develop a method for simultaneous whole-body calcium and phosphorus balance and full kinetic modeling of both ions in patients with chronic kidney disease.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases; Phosphorus and Calcium Disorders; Chronic Kidney Disease Mineral and Bone Disorder
• Intervention / Treatment: Other: High Phosphorus Diet; Other: Low Phosphorus Diet

Detailed Description

The goal of this project is to produce preliminary data on the effects of the commonly prescribed dietary phosphorus restriction on whole-body Calcium (Ca) and Phosphorus (P) balance and kinetics patients with CKD, to support a larger future clinical study. The specific aims are to determine intestinal Ca and P fractional absorption and 2) Ca and P balance and full kinetics, effect sizes variance estimates in patients with CKD on a low Ca diet with high P diet versus dietary P restriction. The hypothesis is that a high P diet, in the context of a typical low Ca diet, leads to P retention negative Ca balance, and that dietary P restriction modestly reduces P retention but does not negative Ca balance.

The study design is a randomized 2-period cross-over study. All outpatient and inpatient visits place at the Indiana CTSI Clinical Research Center located in IU Health University Hospital in Indianapolis, IN. Subjects will be randomly assigned to controlled diets of either low Ca/high P (LCa/HP) or low (LCa/LP) for a 1-week, outpatient diet equilibration period, followed by 1-week inpatient full balance that includes a 48-hour Ca and P absorption testing protocol. After a 1-3 week washout subjects will crossover to the other diet regimen

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana CTSI CRC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men or women, ages 30-75 years old, any race or ethnicity
• Moderate chronic kidney disease
• 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 nutritional 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

Exclusion Criteria:

• Plans to initiate dialysis within 6 months
• Hypercalcemia defined as serum calcium >10.5 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, or bariatric surgery
• Serious, uncontrolled underlying systemic disease including diabetes, lupus, hypertension
• Pregnant or breastfeeding
• Prescribed a phosphate binder medication, calcitriol, vitamin D analogs, calcimimetics, parathyroid hormone analogues, and other medications that may alter Ca and P metabolism within past 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence A; High Phos crossover to Low Phos	Other: High Phosphorus Diet; Controlled research diet of high phosphorus (with low calcium); Other: Low Phosphorus Diet; Controlled research diet of low phosphorus (with low calcium)
Experimental: Sequence B; Low Phos crossover to High Phos	Other: High Phosphorus Diet; Controlled research diet of high phosphorus (with low calcium); Other: Low Phosphorus Diet; Controlled research diet of low phosphorus (with low calcium)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fractional Calcium Absorption	Determined by kinetic modeling of serum and urine Ca-44 isotope after oral and IV isotope administrations	48 hours
Fractional Phosphorus Absorption	Determined by kinetic modeling of serum and urine P-33 isotope after oral and IV isotope administrations	48 hours
Calcium Balance	Determined by analysis of calcium content in complete 24-hour urine and stool collections, subtracted from the diet calcium content consumed. Values can be negative, zero, or positive.	1 week
Phosphorus Balance	Determined by analysis of phosphorus content in complete 24-hour urine and stool collections, subtracted from the diet phosphorus content consumed. Values can be negative, zero, or positive.	1 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Intact Fibroblast Growth Factor 23 (iFGF23)	Determined by enzyme-linked immunoassay (ELISA). Values for each subject are an average of 6 serial measures taken during the 1 week balance period (between Days 1-8)	Day 1-8
Serum Intact Parathyroid Hormone (iPTH)	Determined by enzyme-linked immunoassay (ELISA). Values for each subject are an average of 6 serial measures taken during the 1 week balance period (between Days 1-8)	Day 1-8
Serum 1,25-dihydroxyvitamin D (1,25D)	Determined by LC-MS/MS. Values are from Day 1 of the metabolic balance period (following 1 week of acclimation to assigned study diet).	Day 1

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: Indiana University
• Investigators: Principal Investigator: Kathleen M Hill Gallant, PhD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2020
• Primary Completion (Actual): October 28, 2020
• Study Completion (Actual): January 30, 2023

Study Registration Dates

• First Submitted: July 9, 2019
• First Submitted That Met QC Criteria: July 12, 2019
• First Posted (Actual): July 15, 2019

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Whole-body balance; Kinetic modeling; Intestinal absorption
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Disease Attributes; Renal Insufficiency; Nutrition Disorders; Musculoskeletal Diseases; Parathyroid Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Bone Diseases, Metabolic; Calcium Metabolism Disorders; Rickets; Vitamin D Deficiency; Hyperparathyroidism, Secondary; Hyperparathyroidism; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Bone Diseases; Chronic Kidney Disease-Mineral and Bone Disorder; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium; Calcium, Dietary
• Other Study ID Numbers: 1809583731

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No