Clinical trial NCT04374747: Fruit and Vegetable Intervention in Lactating Women to Reduce Breast Cancer Risk
Official title: Fruit and Vegetable Intervention in Lactating Women to Reduce Breast Cancer Risk: Effects on Breast Cell DNA Methylation, Breast Inflammation,and Weight
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Breast Cancer Female
Inflammation
Postpartum Weight Retention
Diet, Healthy
Risk Reduction
Lead sponsor: University of Massachusetts, Amherst
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-05-05
Enrollment: 400
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: DNA methylation
timeFrame: 20 weeks
measure: Inflammatory markers in milk
timeFrame: 20 weeks
measure: Early weight
timeFrame: 20 weeks
measure: Early waist circumference
timeFrame: 20 weeks
measure: One-year Weight
timeFrame: One-year
measure: One-year Waist Circumference
timeFrame: one year
Secondary outcomes:
Other outcomes:
measure: Fruit and Vegetable Intake
timeFrame: one year
Locations:
city: Amherst
country: United States
facility: University of Massachusetts Amherst
state: Massachusetts
Study officials:
affiliation: University of Massachusetts, Amherst
name: Kathleen Arcaro, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Massachusetts, Amherst
name: Lindiwe Sibeko, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Massachusetts, Amherst
name: Susan Sturgeon, DrPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Sturgeon SR, Sibeko L, Balasubramanian R, Arcaro KF. New Moms Wellness Study: the randomized controlled trial study protocol for an intervention study to increase fruit and vegetable intake and lower breast cancer risk through weekly counseling and supplemental fruit and vegetable box delivery in breastfeeding women. BMC Womens Health. 2022 Sep 24;22(1):389. doi: 10.1186/s12905-022-01967-9.