Chronic Kidney Disease Mineral and Bone Disorder, Chronic Kidney Diseases, Phosphorus and Calcium Disorders
Conditions
Keywords
Whole-body balance, Kinetic modeling, Intestinal absorption
Brief summary
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.
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
Interventions
OTHERHigh Phosphorus Diet
Controlled research diet of high phosphorus (with low calcium)
OTHERLow Phosphorus Diet
Controlled research diet of low phosphorus (with low calcium)
Sponsors
Indiana University
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fractional Calcium Absorption | 48 hours | Determined by kinetic modeling of serum and urine Ca-44 isotope after oral and IV isotope administrations |
| Fractional Phosphorus Absorption | 48 hours | Determined by kinetic modeling of serum and urine P-33 isotope after oral and IV isotope administrations |
| Calcium Balance | 1 week | 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. |
| Phosphorus Balance | 1 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Intact Parathyroid Hormone (iPTH) | Day 1-8 | 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) |
| Serum 1,25-dihydroxyvitamin D (1,25D) | Day 1 | Determined by LC-MS/MS. Values are from Day 1 of the metabolic balance period (following 1 week of acclimation to assigned study diet). |
| Serum Intact Fibroblast Growth Factor 23 (iFGF23) | Day 1-8 | 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence A High Phos crossover to Low Phos
High Phosphorus Diet: Controlled research diet of high phosphorus (with low calcium)
Low Phosphorus Diet: Controlled research diet of low phosphorus (with low calcium) | 1 |
| Sequence B Low Phos crossover to High Phos
Low Phosphorus Diet: Controlled research diet of low phosphorus (with low calcium)
High Phosphorus Diet: Controlled research diet of high phosphorus (with low calcium) | 2 |
| Total | 3 |
Baseline characteristics
| Characteristic | Total | Sequence A | Sequence B |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Continuous | 58 years | 71 years | 52 years |
| body mass index (BMI) | 25.2 kg/m^2 | 34.7 kg/m^2 | 20.5 kg/m^2 |
| estimated glomerular filtration rate (eGFR) | 37 mL/min/1.73m^2 | 40 mL/min/1.73m^2 | 35 mL/min/1.73m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 0 Participants | 2 Participants |
| Serum 1,25-dihydroxyvitamin D3 (1,25D) | 32 pg/mL | 46 pg/mL | 26 pg/mL |
| Serum intact fibroblast growth factor-23 (iFGF23) | 61.4 pg/mL | 27.6 pg/mL | 78.3 pg/mL |
| Serum intact parathyroid hormone (iPTH) | 131.7 pg/mL | 85.5 pg/mL | 154.7 pg/mL |
| Serum phosphorus | 2.6 mg/dL | 2.5 mg/dL | 2.7 mg/dL |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 0 / 3 | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 |
Outcome results
Primary
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.
Time frame: 1 week
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High Phosphorus Diet | Calcium Balance | 126 mg/d |
| Low Phosphorus Diet | Calcium Balance | 199 mg/d |
Primary
Fractional Calcium Absorption
Determined by kinetic modeling of serum and urine Ca-44 isotope after oral and IV isotope administrations
Time frame: 48 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High Phosphorus Diet | Fractional Calcium Absorption | 0.30 fraction of 1.00 |
| Low Phosphorus Diet | Fractional Calcium Absorption | 0.42 fraction of 1.00 |
Primary
Fractional Phosphorus Absorption
Determined by kinetic modeling of serum and urine P-33 isotope after oral and IV isotope administrations
Time frame: 48 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High Phosphorus Diet | Fractional Phosphorus Absorption | 0.73 fraction of 1.00 |
| Low Phosphorus Diet | Fractional Phosphorus Absorption | 0.69 fraction of 1.00 |
Primary
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.
Time frame: 1 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High Phosphorus Diet | Phosphorus Balance | 65 mg/d |
| Low Phosphorus Diet | Phosphorus Balance | 73 mg/d |
Secondary
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).
Time frame: Day 1
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High Phosphorus Diet | Serum 1,25-dihydroxyvitamin D (1,25D) | 29.7 pg/mL |
| Low Phosphorus Diet | Serum 1,25-dihydroxyvitamin D (1,25D) | 29.7 pg/mL |
Secondary
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)
Time frame: Day 1-8
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High Phosphorus Diet | Serum Intact Fibroblast Growth Factor 23 (iFGF23) | 67.9 pg/mL |
| Low Phosphorus Diet | Serum Intact Fibroblast Growth Factor 23 (iFGF23) | 53.4 pg/mL |
Secondary
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)
Time frame: Day 1-8
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High Phosphorus Diet | Serum Intact Parathyroid Hormone (iPTH) | 122.7 pg/mL |
| Low Phosphorus Diet | Serum Intact Parathyroid Hormone (iPTH) | 104.7 pg/mL |