A Low AGE (Advanced Glycation End-product) Dietary Intervention for Breast Cancer Survivors

The scientific premise for this study is the known impact of overweight/obesity on breast cancer risk and outcomes, the association between advanced glycation end-products (AGE) and high fat, highly processed foods common in Western diets, and the preclinical evidence suggesting a link between AGE and breast cancer independent of weight. The association between dietary and serum AGE in breast cancer survivors and prognosis has not been previously evaluated. However, preclinical studies suggest that AGE may represent a novel, lifestyle-linked, modifiable, prognostic biomarker, which could be targeted through lifestyle (diet and exercise) and/or pharmaceutical interventions to improve breast cancer prognosis. The proposed study will pave the way for a large scale randomized controlled trial to evaluate the impact of a low AGE diet on weight (BMI), known (IL-6 and CRP) and novel (AGE and RAGE) prognostic biomarkers, and ultimately on breast cancer prognosis.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Other: Low AGE diet; Procedure: Research blood draw

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of breast cancer, any subtype, stage I-III, within the last 36 months, who have completed primary therapy of their breast cancer (surgery, radiation, and chemotherapy). Must be at least 4 weeks post their last chemotherapy or radiation therapy. Concurrent hormonal therapy is allowed.
• At least 18 years of age.
• Determined to have a high AGE diet at baseline (dietary AGE intake greater than 14 Eq/day as assessed by food frequency questionnaire).
• Ability to understand and willingness to sign an IRB approved written informed consent document.

Exclusion Criteria:

• Diagnosis of diabetes.
• History of eating disorder or body dysmorphic disorder.
• Active tobacco use (tobacco is a source of advanced glycation end products).
• Active participation in other dietary or physical activity clinical trials or community interventions.
• Taking and unwilling/unable to stop taking B-6 (pyridoxamine), B1 (thiamine) or metformin (all known AGE inhibitors).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Low AGE dietary intervention; Patients will complete a food frequency questionnaire, & if found to have a high AGE diet at baseline, will then begin the study the 24-week low AGE dietary intervention. Patients will complete a 3 day food record prior to receiving remotely delivered education on AGEs on how to adhere to a low AGE diet by the study dieticians prior to starting. This session will provide education on dietary AGE & how to prepare & choose low AGE meals; Subsequent sessions with the dieticians will be conducted remotely & will be 30-60 minutes in duration, with the exception of sessions scheduled for weeks when a study blood draw is required, when visits with the dietician may occur in person. These sessions will occur at the following schedule: weekly during the first 2 months (8 sessions), every other week during the next 2 months (4 sessions, aka step down sessions), monthly for the remaining 2 months (2 sessions); 3 day food records will be collected at 12 & 24 weeks, in addition to baseline.

Other: Low AGE diet; The recommended daily AGE intake will be either: 7,500 kilounits [ku], which is a 50% reduction from the average 15,000 ku consumed by most adults or; a 50% reduction from their baseline AGE intake (based on 3-day food AGE record); Procedure: Research blood draw; Baseline (Week 0), Week 4, Week 12, and Week 24 (end of intervention)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility as measured by adherence rate	Feasibility is a defined adherence rate of at least 80% of participants enrolled; Diet adherence will be categorized by the study dietitian at the end of the study and before the results of AGEs in serum or any analysis of outcomes to avoid bias. Following each phone session with the participants, the dietitian will elicit answers to the following question: since the last call did the participant use any cooking methods they were advised to avoid for certain food items? (yes/no).; The information will be used to calculate an adherence score. Adherence score is % phone calls of patient's report for full maintaining instructions to reduce AGEs.; Very high adherence= ≥80%; good adherence= 60-80%; partial adherence= 40-60%; lack of adherence but intention to adhere more in the future= ≤40%; lack of adherence and no intention to adhere more= ≤40%	At study completion for all enrolled participants (estimated to be 15 months)
Feasibility as measured by dropout rate	-Feasibility is defined as a dropout rate of less than 20% of participants enrolled	At study completion for all enrolled participants (estimated to be 15 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in dietary AGE	-Dietary AGE is estimated based on analysis of the 3 day food record patients will complete at baseline and study completion. A specific dietary AGE value will be assigned to each item on the 3 day food recall by consultant and dietary AGE expert Jaime Uribarri, MD. This value is based on his published dietary AGE database which accounts for type of food, portion size and cooking methods.	At baseline and study completion (24 weeks)
Change in serum AGE	Blood specimens for serum AGE analysis will be shipped from the University of San Diego Biorepository to the Medical University of South Carolina to be analyzed in the lab of study team member and expert AGE analyst, Dr. David Turner.; AGE (measured by the AGE metabolite carboxymethyllysine (ug/ml)) will be assessed in serum using commercially available 96-well format ELISA's and ROS detection kits (Cell Biolabs). Nε-carboxymethyllysine (CML) is an AGE metabolite extensively studied in animal models of disease and with regard to food content.	Baseline, week 12, and week 24
Correlation between serum AGE levels and BMI	-The relationship between serum AGE levels and BMI will be assessed using rank based correlation.	Baseline, 12 weeks, and 24 weeks
Correlation between serum AGE levels and serum CRP	-The relationship between serum AGE levels and serum CRP will be assessed using rank based correlation.	Baseline, 12 weeks, and 24 weeks
Correlation between serum AGE levels and IL6	-The relationship between serum AGE levels and IL6 will be assessed using rank based correlation.	Baseline, 12 weeks, and 24 weeks
Correlation between serum AGE levels and glucose	-The relationship between serum AGE levels and glucose will be assessed using rank based correlation.	Baseline, 12 weeks, and 24 weeks
Correlation between serum AGE levels and leptin	-The relationship between serum AGE levels and leptin will be assessed using rank based correlation.	Baseline, 12 weeks, and 24 weeks
Correlation between serum AGE levels and adiponectin	-The relationship between serum AGE levels and adiponectin will be assessed using rank based correlation.	Baseline, 12 weeks, and 24 weeks
Correlation between dietary AGE and BMI	-The relationship between dietary AGE and BMI will be assessed using rank based correlation.	Baseline, 12 weeks, and 24 weeks
Correlation between dietary AGE and serum CRP	-The relationship between dietary AGE and serum CRP will be assessed using rank based correlation.	Baseline, 12 weeks, and 24 weeks
Correlation between dietary AGE and IL6	-The relationship between dietary AGE and IL6 will be assessed using rank based correlation.	Baseline, 12 weeks, and 24 weeks
Correlation between dietary AGE and insulin	-The relationship between dietary AGE and insulin will be assessed using rank based correlation.	Baseline, 12 weeks, and 24 weeks
Correlation between dietary AGE and glucose	-The relationship between dietary AGE and glucose will be assessed using rank based correlation.	Baseline, 12 weeks, and 24 weeks
Correlation between dietary AGE and leptin	-The relationship between dietary AGE and leptin will be assessed using rank based correlation.	Baseline, 12 weeks, and 24 weeks
Correlation between dietary AGE and adiponectin	-The relationship between dietary AGE and adiponectin will be assessed using rank based correlation.	Baseline, 12 weeks, and 24 weeks

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: American Cancer Society, Inc.
• Investigators: Principal Investigator: Lindsay Peterson, M.D., MSCR, Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2022
• Primary Completion (Actual): March 22, 2024
• Study Completion (Actual): March 22, 2024

Study Registration Dates

• First Submitted: January 31, 2022
• First Submitted That Met QC Criteria: February 28, 2022
• First Posted (Actual): March 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 202201100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All research data will be shared between Dr. Peterson and the study team will be available to all investigators named on this proposal. The primary investigators are also willing to share data and materials with other eligible investigators and collaborators through academically established means. Final data will be shared in an openly and timely manner while ensuring the privacy and confidentiality of participants through presentations at scientific seminars and conference and publications in peer reviewed journals. Information about the intervention protocol and survey tools will be made available to others upon request.
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following article presentation.
• IPD Sharing Access Criteria: Proposals should be directed to llpeterson@wustl.edu.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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