Clinical trial NCT03813381: CAlorie and Protein REstriction PROgram in Barrett's Esophagus Patients (CARE-PRO).
Official title: The Impact of a Moderate CAlorie and Protein REstriction PROgram (CARE-PRO) as an Efficient and Affordable Therapeutic Strategy in Patients With Barrett's Esophagus.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Barrett's Esophagus
Overweight and Obesity
Keywords: Esophageal adenocarcinoma
Diet
Physical activity
Microbiota
Lead sponsor: Istituto Oncologico Veneto IRCCS
Sponsor class: OTHER
First posted: 2019-01-23
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The increasing incidence of Esophageal Adenocarcinoma (EAC) in several Western countries can be primarily ascribed to risk factors such as obesity, chronic gastroesophageal reflux, dietary habits and alcohol intake. Nevertheless, Barrett's Esophagus (BE), remains the main risk factor for EAC. Several studies supports the role played by the gut microbiota on the modulation of metabolic and immunological pathways. An abnormal state of the microbial ecosystem seems to be involved in the promotion and onset of various diseases, including cancer. Recent studies have shown that diet and lifestyle have an important modulatory role as protective or risk factors for oncological diseases. The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) released a review of the evidence that emerged from published studies in the field of nutrition and cancer prevention and summarized their findings into 10 recommendations. Several studies have also shown that a moderate caloric and/or protein restriction seems to be able to reduce the risk of neoplastic disease development. The primary aim of this study is to evaluate the impact of a lifestyle-oriented intervention on body weight, waist circumference, biomarkers associated with cancer risk, esophageal microbiota composition and adherence to cancer prevention recommendations after 24 months in overweight or obese BE patients.

Methods and analysis: Patients are randomly divided into two arms, a control arm (CA) and an interventional arm (IA). The CA receives information about a correct lifestyle to prevent cancer.

The IA is involved in the two-year program of moderate caloric and protein restriction.

At the time of enrollment, anthropometric measurements will be recorded for each patient and they will be randomized to IA or CA. Blood samples will be obtained from each patient and blood glucose will be determined. Serum metabolic biomarkers will be measured in each serum sample and total proteins will be extracted from fresh frozen esophageal biopsy and will be analyzed to evaluate the insulin signal pathway.

To assess esophageal microbiota profiling, total genomic DNA (gDNA) will be extracted from matched fresh frozen biopsy.

In order to determine a score of adherence to cancer prevention recommendations, participants will be asked to complete a self-administrated questionnaire reflecting WCRF/AICR recommendations.

All the measurements will also occur at the end point, after two years from the enrollment.


Eligibility criteria: Inclusion Criteria:

* Histological confirmation of Barrett's esophagus without dysplasia or cancer aged ≥ 18 years with BMI ≥ 25.0 kg/m\^2
* Willingness and ability to perform supervised Nordic walking session twice a month and self-planned physical activity at least 3 times a week
* Signed informed consent

Exclusion Criteria:

* No histological confirmation of Barrett's esophagus
* Cancer diagnosis within one year before trial begins
* Presence of insulin-dependent diabetes
* Denied informed consent

Primary outcomes:
measure: Body weight change
timeFrame: Baseline and after 24 months
Secondary outcomes:
measure: Metabolic serum biomarkers
timeFrame: Baseline and after 24 months
measure: Metabolic serum biomarkers
timeFrame: Baseline and after 24 months
measure: Metabolic serum biomarkers
timeFrame: Baseline and after 24 months
measure: Metabolic serum biomarkers
timeFrame: Baseline and after 24 months
measure: Metabolic serum biomarkers
timeFrame: Baseline and after 24 months
measure: Insulin resistance index (HOMA-IR)
timeFrame: Baseline and after 24 months
measure: Expression of proteins involved on insulin and IGF1 receptors signal transduction
timeFrame: Baseline and after 24 months
measure: Esophageal microbiota composition
timeFrame: Baseline and after 24 months
measure: Adherence score to World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR) recommendations for cancer prevention.
timeFrame: Baseline and after 24 months
measure: Waist circumference reduction
timeFrame: Baseline and after 24 months
Other outcomes:
Locations:
Study officials:
affiliation: Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
name: Stefano Realdon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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