Fruit and Vegetable Intervention in Lactating Women to Reduce Breast Cancer Risk

Inflammation Clinical Trial

Official title:

Fruit and Vegetable Intervention in Lactating Women to Reduce Breast Cancer Risk: Effects on Breast Cell DNA Methylation, Breast Inflammation,and Weight

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04374747
• Other study ID #: 2019-5382
• Secondary ID: 1R01CA230478-01A
• Status: Recruiting
• Phase: N/A
• Start date: October 24, 2019
• Est. completion date: April 1, 2024

Study information

• Verified date: April 2022
• Source: University of Massachusetts, Amherst
• Contact: Kathleen Arcaro, PhD
• Phone: 413-577-1823
• Email: karcaro[@]umass.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Mechanistic data show that compounds in fruits and vegetables have anti-inflammatory and anti-carcinogenic properties that can reduce breast cancer risk. However, observational and interventional studies have provided mixed results, and a recent report by the American Institute for Cancer Research (AICR) concludes that the data are insufficient but suggestive that non-starchy vegetables and foods containing carotenoids reduce risk. Measurement error, relatively low levels of carotenoid-rich fruit and vegetable intake in the study populations, emphasis on diet in later adulthood, and confounding factors likely contribute to the weak associations. Therefore, the investigators will conduct a randomized diet intervention trial in young women to assess the extent to which at least 8 to 10 daily servings of deeply pigmented and nutrient dense fruits and vegetables reduces biomarkers of breast cancer risk. The intervention is focused on breastfeeding women because: 1) pregnancy and lactation are normal early life course events; 2) the risk of pregnancy-associated breast cancer (PABC) is increased for up to 10 years postpartum; 3) a dietary intervention to reverse the detrimental molecular changes associated with puberty and pregnancy is more likely to be successful in younger than in older women;4) a diet rich in fruits and vegetables is hypothesized to reduce the inflammation during lactation/weaning and lower PABC risk; 5) postpartum lactating women may be a highly motivated population; and 6) breastmilk provides access to the breast microenvironment and breast epithelial cells to non-invasively assess the diet intervention directly in the breast. Four hundred nursing mothers will be randomly assigned to either the intervention arm, in which they are asked to increase fruit and vegetable intake to at least 8 to 10 daily servings for one year, or to a control condition in which participants receive a dietary guideline for breastfeeding mothers. Women in the intervention arm will receive counseling and boxes of fruits and vegetables for the first 20 weeks, after which they will continue to receive counseling. Changes in DNA methylation and cytokine profiles in breastmilk will be evaluated. Maternal weight and body fat distribution, and infant growth will be monitored. These results will greatly expand our knowledge of how diet alters molecular pathways in a specific organ, ultimately contributing to both breast cancer etiology and prevention.

Description:

Overview of home visits and activities completed by all participants Visit 1 Introductory Visit (1.5 hours) 24-Hour Dietary Recalls completed during the week (1-2 hours) Occurs at 5 weeks postpartum - Informed Consent document administered. - Public Data Sharing Informed Consent document administered. - Three questionnaires: New Moms Health, Physical Activity, and Breastfeeding Practices - Maternal height, weight, and waist circumference measured. - Instructions provided for future collection of biospecimens. - Complete one 24-Hour Dietary Recall - Instructions provided for two additional 24-Hour Dietary Recalls. Visit 2 Sample Collection 1 (1.5 hours) Occurs at 6 weeks postpartum - Provide bilateral breast milk samples and completed questionnaire. - Provide infant stool sample and completed questionnaire. - Two questionnaires: Infant Feeding, and Medication & Supplement - Infant length and weight measured. - Maternal and infant skin carotenoids measured. - Nutrition education provided. - Optional collection of maternal stool sample and completed questionnaire. Visit 3 Sample Collection 2 (1.5 hours) 24-Hour Dietary Recalls completed during the week (1-2 hours) Occurs at 16 weeks postpartum - Provide bilateral breast milk samples and completed questionnaire. - Provide infant stool sample and completed questionnaire. - Three questionnaires: Physical Activity, Infant Feeding, and Medication & Supplement - Infant length and weight measured. - Maternal weight and waist circumference measured. - Maternal and infant skin carotenoids measured. Visit 4 Sample Collection 3 (1.5 hours) 24-Hour Dietary Recalls completed during the week (1-2 hours) Occurs at 26 weeks postpartum - Provide bilateral breast milk samples and completed questionnaire. - Provide infant stool sample and completed questionnaire. - Three questionnaires: Physical Activity, Infant Feeding, and Medication & Supplement. - Infant length and weight measured. - Maternal weight and waist circumference measured. - Maternal and infant skin carotenoids measured. - Optional collection of maternal stool samples and completed questionnaire. Visit 5 Sample Collection 4 (1.5 hours) 24-Hour Dietary Recalls completed during the week (1-2 hours) Occurs at 58 weeks postpartum - Provide bilateral breast milk samples and completed questionnaire. - Provide infant stool sample and completed questionnaire. - Four questionnaires: Physical Activity, Infant Feeding, Medication and Supplement, and Breast Health - Infant length and weight measured. - Maternal weight and waist circumference measured. - Maternal and infant skin carotenoids measured. - Optional collection of maternal stool samples and completed questionnaire. Annual Follow-up Visit (Maximum of 2) (1 hour) 24-Hour Dietary Recalls completed during the week (1-2 hours) Occurs at one-year intervals after Visit 5 - Three questionnaires: Physical Activity, Breast Health, Young Child Feeding - Infant height and weight measured. - Maternal weight and waist circumference measured. - Maternal and infant skin carotenoids measured. Monthly Inquiry (1 - 2 minutes) Occurs monthly until no longer breastfeeding • Complete the Breast Feeding Update Questionnaire online via a survey sent through REDCap, or through a phone call.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: April 1, 2024
• Est. primary completion date: April 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have given birth in past five weeks or are currently pregnant
• Breastfeeding baby at entry into the study
• Consuming five or fewer servings of fruits and vegetables daily at baseline
• Live within 25 miles of Amherst MA

Exclusion Criteria:

• Invasive breast cancer
• Any cancer except non-melanoma skin cancer in past five years
• History of Crohn's disease, celiac sprue, or other malabsorption syndrome, which may interfere with digesting or absorption of nutrients
• A personal history of diabetes (excluding gestational diabetes)
• Baseline BMI of <18.5
• Dietary restrictions that prevent participant from eating 8 to 10 servings of fruits and vegetables

Related Conditions & MeSH terms

• Breast Cancer Female
• Breast Neoplasms
• Diet, Healthy
• Gestational Weight Gain
• Inflammation
• Postpartum Weight Retention
• Risk Reduction

Intervention

Behavioral:
• Dietary Counseling
The counseling approach will employ strategies shown to be successful in previous and ongoing dietary modification studies including supportive and motivational interviewing techniques. Each woman in the diet intervention group will be assigned a trained nutrition coach/counselor. Counselors will focus on helping participants identify and address barriers to achieving the goal of consuming at least 8 to 10 servings of nutrient dense fruits and vegetables each day (e.g., modifying recipes and food preparation). Participants will also receive weekly boxes of fruits and vegetables .

Locations

Country	Name	City	State
United States	University of Massachusetts Amherst	Amherst	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
University of Massachusetts, Amherst	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Essa AR, Browne EP, Punska EC, Perkins K, Boudreau E, Wiggins H, Anderton DL, Sibeko L, Sturgeon SR, Arcaro KF. Dietary Intervention to Increase Fruit and Vegetable Consumption in Breastfeeding Women: A Pilot Randomized Trial Measuring Inflammatory Markers in Breast Milk. J Acad Nutr Diet. 2018 Dec;118(12):2287-2295. doi: 10.1016/j.jand.2018.06.015. Epub 2018 Sep 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Fruit and Vegetable Intake	servings per day	one year
Primary	DNA methylation	% methylation in 300,000 CpG sites in DNA from sloughed breast epithelial cells from milk	20 weeks
Primary	Inflammatory markers in milk	Adiponectin, CRP, IFN-y, IL1-beta, Leptin, IL-6, IL-8, TNF-alpha, b-FGF, FLT-1, PLGF, VegF-D	20 weeks
Primary	Early weight	maternal weight	20 weeks
Primary	Early waist circumference	maternal waist circumference	20 weeks
Primary	One-year Weight	maternal weight	One-year
Primary	One-year Waist Circumference	maternal weight circumference	one year