Oxalate-Driven Host Responses in Kidney Stone Disease

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05417568
• Collaborator: National Institutes of Health (NIH) (NIH)
• Enrollment: 88
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 53.9
• Patients Per Site Per Month: 1.6

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Stones	Dietary Supplement: Low Oxalate Diet; Dietary Supplement: High Oxalate Diet	N/A

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Oxalate-Driven Host Responses in Kidney Stone Disease
• Anticipated Study Start Date: Oct 1, 2022
• Anticipated Primary Completion Date: Mar 30, 2027
• Anticipated Study Completion Date: Mar 30, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Healthy Participants 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.	Dietary Supplement: Low Oxalate Diet; 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.; Dietary Supplement: High Oxalate Diet; 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.
Experimental: Calcium Oxalate Kidney Stone 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.	Dietary Supplement: Low Oxalate Diet; 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.; Dietary Supplement: High Oxalate Diet; 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.

Outcome Measures

Primary Outcome Measures

1. Change in Urinary Oxalate [Days 3-4 and 13-14]

   Twenty-four hour urinary oxalate will be reported as mg/day.

2. Change in Nanocystalluria [Days 3-4 and 13-14]

   Nanocrystalluria will be reported as particles/ml.

3. Monocyte Cellular Bioenergetics and Mitochondrial Function [Day 1]

   Cellular bioenergetics and mitochondrial function will be reported as oxygen consumption rate (pmol/min/10,000 cells).

4. Monocyte Cellular Bioenergetics and Mitochondrial Function [Day 4]

   Cellular bioenergetics and mitochondrial function will be reported as oxygen consumption rate (pmol/min/10,000 cells).

5. Monocyte Cellular Bioenergetics and Mitochondrial Function [Day 11]

   Cellular bioenergetics and mitochondrial function will be reported as oxygen consumption rate (pmol/min/10,000 cells).

6. Monocyte Cellular Bioenergetics and Mitochondrial Function [Day 14]

   Cellular bioenergetics and mitochondrial function will be reported as oxygen consumption rate (pmol/min/10,000 cells).

7. Monocyte Subtypes [Day 1]

   Monocyte subtypes will be determined using flow cytometry (mean fluorescence intensity).

8. Monocyte Subtypes [Day 4]

   Monocyte subtypes will be determined using flow cytometry (mean fluorescence intensity).

9. Monocyte Subtypes [Day 11]

   Monocyte subtypes will be determined using flow cytometry (mean fluorescence intensity).

10. Monocyte Subtypes [Day 14]

    Monocyte subtypes will be determined using flow cytometry (mean fluorescence intensity).

11. Monocyte Transcriptomics [Day 1]

    Monocyte transcriptomics will be reported as gene expression (mRNA levels)

12. Monocyte Transcriptomics [Day 4]

    Monocyte transcriptomics will be reported as gene expression (mRNA levels)

13. Monocyte Transcriptomics [Day 11]

    Monocyte transcriptomics will be reported as gene expression (mRNA levels)

14. Monocyte Transcriptomics [Day 14]

    Monocyte transcriptomics will be reported as gene expression (mRNA levels)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294

Sponsors and Collaborators

• University of Alabama at Birmingham
• National Institutes of Health (NIH)

Investigators

• Principal Investigator: Tanecia Mitchell, PhD, University of Alabama at Birmingham

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tanecia Mitchell, PhD, Principal Investigator, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT05417568
• Other Study ID Numbers: IRB-300009093
• First Posted: Jun 14, 2022
• Last Update Posted: Jun 14, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Tanecia Mitchell, PhD, Principal Investigator, University of Alabama at Birmingham: Kidney stones; Dietary oxalate
• Additional relevant MeSH terms: Kidney Calculi; Nephrolithiasis; Calculi

Study Results

No Results Posted as of Jun 14, 2022