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Oxalate-Driven Host Responses in Kidney Stone Disease

Primary Purpose

Kidney Stones

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Low Oxalate Diet
High Oxalate Diet
Sponsored by
University of Alabama at Birmingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Kidney Stones focused on measuring Kidney stones, Dietary oxalate

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Men and women between the ages of 18 and 60 years old.
  • Able to provide informed consent.
  • BMI between 20-30 kg/m2.
  • Non-tobacco users or not pregnant/breastfeeding/nursing.
  • Normal fasting blood comprehensive metabolic panel, complete blood count, C-reactive protein, and urinalysis. Must accurately collect two 24-hour urine collections within 20% of the appropriate ratio of creatinine (mg)/body weight (kg) for respective gender.
  • Healthy subjects: No history of CaOx KS or other medical conditions.
  • Patients with CaOx KS: Recent stone composition > 50% CaOx; no uric acid, struvite, or carbonate apatite stone content. Must be first-time or recurrent CaOx stone former (last stone event ≤ 3 years).
  • Willing to not consume supplements (i.e. vitamins, Ca (citrate or carbonate) and other minerals, herbal supplements, nutritional aids, and probiotics) for 2 weeks before the study and during the study.
  • Willing to abstain from vigorous exercise during the study as this may compromise immune function.
  • Willing to consume diets provided only by the UAB CCTS Bionutrition Core. No food allergies or intolerance to any of the foods on the study menus.
  • Willing to accurately collect 24-hour urine samples, and to have blood drawn throughout the study.
  • If on medications for KS prevention (e.g. thiazides, citrate supplementation excluding calcium citrate), patients must be on a stable dose regimen for at least 8 weeks prior to and during screening, with no changes in dosing anticipated during the study. Patients should not take allopurinol for 2 weeks prior to screening since allopurinol has antioxidant properties.

Exclusion Criteria:

  • Failure to meet the inclusion criteria or physician refusal.
  • Inability to sign and read the informed consent.
  • Any medical, psychiatric, or social conditions that would prohibit participants from abiding by the study requirements.
  • BMI ˃30 kg/m2 and <20 kg/m2
  • Tobacco users or pregnant or breastfeeding/nursing women.
  • Abnormal fasting blood comprehensive metabolic panel, complete blood count, C-reactive protein, and urinalysis. Inaccurate 24-hour urine collections.
  • Healthy subjects: Currently taking or have recently taken medications within the last 3 months (i.e. antibiotics) or dietary supplements. History of KS or any medical condition that could influence absorption or excretion of oxalate.
  • Active illness including COVID-19, flu, common cold, fever, diarrhea, urinary tract infections, or other infections 14 days before the study and throughout the study.

Sites / Locations

  • University of Alabama at BirminghamRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Healthy Participants

Calcium Oxalate Kidney Stone

Arm Description

Healthy participants will randomly receive either high (250mg) or low (40mg) oxalate diet for for four days, a ten day "washout" period on a self-selected diet, and finally the opposite diet from the first for the last four days.

Calcium oxalate kidney stone participants will randomly receive either high (250mg) or low (40mg) oxalate diet for for four days, a ten day "washout" period on a self-selected diet, and finally the opposite diet from the first for the last four days.

Outcomes

Primary Outcome Measures

Change in Urinary Oxalate
Twenty-four hour urinary oxalate will be reported as mg/day.
Change in Nanocystalluria
Nanocrystalluria will be reported as particles/ml.
Monocyte Cellular Bioenergetics and Mitochondrial Function
Cellular bioenergetics and mitochondrial function will be reported as oxygen consumption rate (pmol/min/10,000 cells).
Monocyte Cellular Bioenergetics and Mitochondrial Function
Cellular bioenergetics and mitochondrial function will be reported as oxygen consumption rate (pmol/min/10,000 cells).
Monocyte Cellular Bioenergetics and Mitochondrial Function
Cellular bioenergetics and mitochondrial function will be reported as oxygen consumption rate (pmol/min/10,000 cells).
Monocyte Cellular Bioenergetics and Mitochondrial Function
Cellular bioenergetics and mitochondrial function will be reported as oxygen consumption rate (pmol/min/10,000 cells).
Monocyte Subtypes
Monocyte subtypes will be determined using flow cytometry (mean fluorescence intensity).
Monocyte Subtypes
Monocyte subtypes will be determined using flow cytometry (mean fluorescence intensity).
Monocyte Subtypes
Monocyte subtypes will be determined using flow cytometry (mean fluorescence intensity).
Monocyte Subtypes
Monocyte subtypes will be determined using flow cytometry (mean fluorescence intensity).
Monocyte Transcriptomics
Monocyte transcriptomics will be reported as gene expression (mRNA levels)
Monocyte Transcriptomics
Monocyte transcriptomics will be reported as gene expression (mRNA levels)
Monocyte Transcriptomics
Monocyte transcriptomics will be reported as gene expression (mRNA levels)
Monocyte Transcriptomics
Monocyte transcriptomics will be reported as gene expression (mRNA levels)

Secondary Outcome Measures

Full Information

First Posted
June 6, 2022
Last Updated
May 31, 2023
Sponsor
University of Alabama at Birmingham
Collaborators
National Institutes of Health (NIH)
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1. Study Identification

Unique Protocol Identification Number
NCT05417568
Brief Title
Oxalate-Driven Host Responses in Kidney Stone Disease
Official Title
Oxalate-Driven Host Responses in Kidney Stone Disease
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 19, 2023 (Actual)
Primary Completion Date
May 30, 2027 (Anticipated)
Study Completion Date
May 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham
Collaborators
National Institutes of Health (NIH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is looking to understand the role of oxalate on kidney stone development and immunity. This study will enroll healthy participants and participants with calcium oxalate kidney stones (CaOx KS). Participants will be in this study for about 3 weeks, consume controlled diets, and provide blood and urine specimens.
Detailed Description
The purpose of this longitudinal study is to examine the effects of dietary oxalate on nanocrystalluria and the immune system. Oxalate is a small molecule found in plants and plant-derived food. It has been shown that meals containing high amounts of oxalate can increase urinary oxalate excretion, which is a risk factor for calcium oxalate kidney stones (CaOx KS). Small increases in oxalate can stimulate urinary crystals to form which can elicit an immune response. This study consists of having healthy subjects and patients with CaOx KS consume both low and oxalate enriched diets to evaluate the effect of oxalate on urinary crystals and immune responses. Participants will receive a low or high oxalate diet for 4 days prior to having a wash-out period for 6 days. Participants will then crossover to the opposite oxalate diet for four more days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Stones
Keywords
Kidney stones, Dietary oxalate

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
88 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Healthy Participants
Arm Type
Experimental
Arm Description
Healthy participants will randomly receive either high (250mg) or low (40mg) oxalate diet for for four days, a ten day "washout" period on a self-selected diet, and finally the opposite diet from the first for the last four days.
Arm Title
Calcium Oxalate Kidney Stone
Arm Type
Experimental
Arm Description
Calcium oxalate kidney stone participants will randomly receive either high (250mg) or low (40mg) oxalate diet for for four days, a ten day "washout" period on a self-selected diet, and finally the opposite diet from the first for the last four days.
Intervention Type
Dietary Supplement
Intervention Name(s)
Low Oxalate Diet
Intervention Description
Participants will consume a diet that is controlled in its daily contents of oxalate and calcium, and in its content of carbohydrate, fat, and protein. Participants will be asked not to take any dietary supplements, exercise strenuously, or consume food or drink that is not provided to them.
Intervention Type
Dietary Supplement
Intervention Name(s)
High Oxalate Diet
Intervention Description
Participants will consume a diet that is controlled in its daily contents of oxalate and calcium, and in its content of carbohydrate, fat, and protein. Participants will be asked not to take any dietary supplements, exercise strenuously, or consume food or drink that is not provided to them.
Primary Outcome Measure Information:
Title
Change in Urinary Oxalate
Description
Twenty-four hour urinary oxalate will be reported as mg/day.
Time Frame
Days 3-4 and 13-14
Title
Change in Nanocystalluria
Description
Nanocrystalluria will be reported as particles/ml.
Time Frame
Days 3-4 and 13-14
Title
Monocyte Cellular Bioenergetics and Mitochondrial Function
Description
Cellular bioenergetics and mitochondrial function will be reported as oxygen consumption rate (pmol/min/10,000 cells).
Time Frame
Day 1
Title
Monocyte Cellular Bioenergetics and Mitochondrial Function
Description
Cellular bioenergetics and mitochondrial function will be reported as oxygen consumption rate (pmol/min/10,000 cells).
Time Frame
Day 4
Title
Monocyte Cellular Bioenergetics and Mitochondrial Function
Description
Cellular bioenergetics and mitochondrial function will be reported as oxygen consumption rate (pmol/min/10,000 cells).
Time Frame
Day 11
Title
Monocyte Cellular Bioenergetics and Mitochondrial Function
Description
Cellular bioenergetics and mitochondrial function will be reported as oxygen consumption rate (pmol/min/10,000 cells).
Time Frame
Day 14
Title
Monocyte Subtypes
Description
Monocyte subtypes will be determined using flow cytometry (mean fluorescence intensity).
Time Frame
Day 1
Title
Monocyte Subtypes
Description
Monocyte subtypes will be determined using flow cytometry (mean fluorescence intensity).
Time Frame
Day 4
Title
Monocyte Subtypes
Description
Monocyte subtypes will be determined using flow cytometry (mean fluorescence intensity).
Time Frame
Day 11
Title
Monocyte Subtypes
Description
Monocyte subtypes will be determined using flow cytometry (mean fluorescence intensity).
Time Frame
Day 14
Title
Monocyte Transcriptomics
Description
Monocyte transcriptomics will be reported as gene expression (mRNA levels)
Time Frame
Day 1
Title
Monocyte Transcriptomics
Description
Monocyte transcriptomics will be reported as gene expression (mRNA levels)
Time Frame
Day 4
Title
Monocyte Transcriptomics
Description
Monocyte transcriptomics will be reported as gene expression (mRNA levels)
Time Frame
Day 11
Title
Monocyte Transcriptomics
Description
Monocyte transcriptomics will be reported as gene expression (mRNA levels)
Time Frame
Day 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Men and women between the ages of 18 and 60 years old. Able to provide informed consent. BMI between 20-30 kg/m2. Non-tobacco users or not pregnant/breastfeeding/nursing. Normal fasting blood comprehensive metabolic panel, complete blood count, C-reactive protein, and urinalysis. Must accurately collect two 24-hour urine collections within 20% of the appropriate ratio of creatinine (mg)/body weight (kg) for respective gender. Healthy subjects: No history of CaOx KS or other medical conditions. Patients with CaOx KS: Recent stone composition > 50% CaOx; no uric acid, struvite, or carbonate apatite stone content. Must be first-time or recurrent CaOx stone former (last stone event ≤ 3 years). Willing to not consume supplements (i.e. vitamins, Ca (citrate or carbonate) and other minerals, herbal supplements, nutritional aids, and probiotics) for 2 weeks before the study and during the study. Willing to abstain from vigorous exercise during the study as this may compromise immune function. Willing to consume diets provided only by the UAB CCTS Bionutrition Core. No food allergies or intolerance to any of the foods on the study menus. Willing to accurately collect 24-hour urine samples, and to have blood drawn throughout the study. If on medications for KS prevention (e.g. thiazides, citrate supplementation excluding calcium citrate), patients must be on a stable dose regimen for at least 8 weeks prior to and during screening, with no changes in dosing anticipated during the study. Patients should not take allopurinol for 2 weeks prior to screening since allopurinol has antioxidant properties. Exclusion Criteria: Failure to meet the inclusion criteria or physician refusal. Inability to sign and read the informed consent. Any medical, psychiatric, or social conditions that would prohibit participants from abiding by the study requirements. BMI ˃30 kg/m2 and <20 kg/m2 Tobacco users or pregnant or breastfeeding/nursing women. Abnormal fasting blood comprehensive metabolic panel, complete blood count, C-reactive protein, and urinalysis. Inaccurate 24-hour urine collections. Healthy subjects: Currently taking or have recently taken medications within the last 3 months (i.e. antibiotics) or dietary supplements. History of KS or any medical condition that could influence absorption or excretion of oxalate. Active illness including COVID-19, flu, common cold, fever, diarrhea, urinary tract infections, or other infections 14 days before the study and throughout the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tanecia Mitchell, PhD
Phone
(205) 996-2292
Email
taneciamitchell@uabmc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tanecia Mitchell, PhD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tanecia Mitchell, PhD
Phone
205-996-2292
Email
taneciamitchell@uabmc.edu
First Name & Middle Initial & Last Name & Degree
Tanecia Mitchell, PhD

12. IPD Sharing Statement

Learn more about this trial

Oxalate-Driven Host Responses in Kidney Stone Disease

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