Effects of Replacing High Protein Foods in People With Chronic Kidney Disease

The Effects of Replacing Red Meat With Alternative Protein Sources on Gut-Derived Metabolites in People With Chronic Kidney Disease

The goal of this crossover clinical trial is to explore the effects of red meat intake on serum and fractional urinary excretion of uremic toxins including trimethylamine N-oxide in people with chronic kidney disease.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Disease Stage 3
• Intervention / Treatment: Other: Controlled dietary intervention

Detailed Description

This study will be a single-blind crossover, human-feeding study comparing 3 weeks of a lacto-ovo vegetarian diet to the same diet with 20% of the protein replaced by red meat. There will be a 2-week baseline period and a 5-week washout period where participants will consume their typical, self-selected diet. Once eligible, the participant will be randomized to a diet order. The investigators will recruit up to 15 participants. Descriptive statistics (means and standard deviations) will be used to summarize the characteristics of the study population. In general, data will be analyzed using linear mixed-effect models to account for the potential correlation among measurements from the same participant. A power analysis of this pilot study will be conducted based on the estimated interparticipant and intraparticipant variabilities to estimate the required number of participants to detect a certain size of difference with a certain power for a full study.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Brandon Kistler; Phone Number: 765-494-5406; Email: bmkistle@purdue.edu

Study Locations

• United States
  • Indiana
    • West Lafayette, Indiana, United States, 47906
      • Recruiting
      • Purdue University
      • Contact: Brandon Kistler; Phone Number: 7654945406; Email: bmkistle@purdue.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 40-70 years
• Male or postmenopausal female
• Stage 3 CKD (eGFR between 30-59ml/min/1.73m^2 by the CKD-EPI equation (without race correction)).
• If eGFR is greater than or equal to 45ml/min/1.73m^2 then albuminuria must be greater than 300mg/g creatinine by spot urine.
• Willing to consume controlled diet for duration of the study
• Willing to collect fecal samples at home

Exclusion Criteria:

• Hemoglobin A1c greater than 7% within previous six months
• Treatment with metformin or insulin within previous three months
• Blood pressure greater than 150/100 mmHg from chart of home on at least two occasions in prior month (can be inclusive of screening visit)
• Change in cardiovascular and/or hypertension medication in the last 30 days
• History of major gastrointestinal disease (e.g. inflammatory bowel disease, uncontrolled irritable bowel syndrome, C. difficile chronic infection, celiac disease, diverticulitis, stomach or duodenal ulcers)
• Known HIV disease
• Hospitalization in the last two months
• Significant recent unintentional weight loss (5% of weight over past three months)
• Cancer or received cancer treatment in the last year (except basal cell carcinoma)
• Prior bariatric surgery (i.e. gastric bypass, sleeve gastrectomy) or restrictive bariatric surgery (i.e. adjustable gastric band)
• Treatment with immunosuppressive medications in the past six months or more than one week of treatment with prednisone greater than 10mg per day in the past three months (or equivalent steroid dose of non-prednisone steroids)
• Recent antibiotic use defined as a single course of antibiotics within the past three months or two or more courses within the past six months
• Known food allergy that would influence the ability to consume the study diets
• History of hyperkalemia defined as greater than 5.5mmol/L on at least two occasions
• Other medical conditions or concerns at the discretion of the investigators

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lacto-ovo vegetarian diet alone; then lacto-ovo vegetarian with red meat diet; Participants will be assigned to a lacto-ovo vegetarian diet providing 0.8 g/kg/day of protein for the first treatment period; they will then be assigned to continue this diet with 20% of the protein replaced by red meet for the second treatment period.	Other: Controlled dietary intervention; Participants will complete a 2-week baseline period consuming their standard diet without any food or beverages provided followed by a randomized, crossover-controlled feeding study of a lacto-ovo vegetarian diet versus the same diet with 20% of the protein replaced by red meat. In between the two diets, there will be a five-week washout where participants will consume their standard diet without any food or beverages provided.
Experimental: Lacto-ovo vegetarian with red meat diet; then lacto-ovo vegetarian diet alone; Participants will be assigned to a lacto-ovo vegetarian diet with 20% of the protein replaced by red meat for the first treatment period; they will then be assigned to a lacto-ovo vegetarian diet alone for the second treatment period.	Other: Controlled dietary intervention; Participants will complete a 2-week baseline period consuming their standard diet without any food or beverages provided followed by a randomized, crossover-controlled feeding study of a lacto-ovo vegetarian diet versus the same diet with 20% of the protein replaced by red meat. In between the two diets, there will be a five-week washout where participants will consume their standard diet without any food or beverages provided.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum trimethylamine N-oxide	Intra- and interparticipant variability of serum concentrations as measured by high performance liquid chromatography-mass spectrometry	13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional serum uremic toxins	Including p-cresyl sulfate and indoxyl sulfate measured by high performance liquid chromatography-mass spectrometry	13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Urinary excretion of uremic toxins	Measured by a ratio of serum and urine values	13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Gut microbiota	Diversity and composition of the gut microbiome	13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Gastrointestinal symptoms	Measured at the end of each study period by the Gastrointestinal Symptom Rating Scale. This is a 15-item questionnaire that includes five domains. Each item is scored from 1 to 7 and the mean score in each domain is presented.	13 Weeks (collections in week 2, 5, 10, and 13 which corresponds to before and during the last week of each of the three-week controlled diet periods).
Stool consistency	Measured on a scale from 1 to 7 using the Bristol Stool Scale/Chart.	13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Blood pressure		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Arterial Stiffness	Carotid-femoral pulse wave velocity	13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Height		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Weight		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Handgrip Strength		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Total cholesterol		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
High density lipoprotein		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Low Density Lipoprotein		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Triglycerides		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Apolipoprotein B		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Blood glucose	Fasting blood glucose	13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Serum calcium		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Serum Potassium		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Serum bicarbonate		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Subjective global assessment	Scored on a scale from 1-7 (severely malnourished to well nourished)	13 Weeks (collections in week 2, 5, 10, 13 which corresponds to before and during the last week of each of the three-week controlled diet periods).
Albumin to creatinine ratio		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Blood urea nitrogen		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Creatinine		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Serum Phosphate		13 Weeks (collections in week 1, 2, 4, 5, 9, 10, 12, 13 which corresponds to before and during the last two weeks of each of the three-week controlled diet periods).
Urinary phosphorus excretion	From 24-hour urine collection	13 Weeks (collections in week 2, 5, 10, 13 which corresponds to before and after each of the three-week controlled diet periods).

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: National Center for Advancing Translational Sciences (NCATS)

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: July 30, 2025
• First Submitted That Met QC Criteria: July 30, 2025
• First Posted (Actual): August 6, 2025

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Renal Insufficiency, Chronic
• Other Study ID Numbers: 25168; K12TR004415 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No