Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers (LIBRE-2)

Prospective Randomized Multicenter Trial to Assess the Efficacy of a Structured Physical Exercise Training and Mediterranean Diet in Women With BRCA1/2 Mutations

The hypothesis of this 3 year, prospective randomized multicenter efficacy trial is that a structured life-style intervention program with exercise training and mediterranean diet is effective regarding increased adherence to a mediterranean diet, reduction of body mass index, and increase of physical fitness.

Study Overview

• Status: Recruiting
• Conditions: Hereditary Breast and Ovarian Cancer
• Intervention / Treatment: Behavioral: Structured exercise training plus mediterranean diet

Detailed Description

BRCA1/2 mutation carriers have a considerably increased risk to develop breast and ovarian cancer during their lifetime. There is evidence from the literature that for sporadic breast cancer disease risk and the course of disease can be significantly influenced by physical activity, nutrition and weight. The hypothesis of this 3 year, prospective randomized multicenter efficacy trial is that a structured life-style intervention program with exercise training and mediterranean diet is effective regarding increased adherence to a mediterranean diet, reduction of body mass index, and increase of physical fitness.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marion Kiechle, Prof. Dr.; Phone Number: +49 89 4140 2420; Email: marion.kiechle@tum.de
• Study Contact Backup: Name: Daniela Schemmer; Phone Number: +49 89 4140 2433; Email: Daniela.Schemmer@mri.tum.de

Study Locations

• Germany
  • Berlin, Germany
    • Recruiting
    • Humboldt Universität zu Berlin
  • Dresden, Germany
    • Recruiting
    • Universitatsklinikum Carl Gustav Carus An Der Technischen Universitat Dresden
  • Düsseldorf, Germany
    • Recruiting
    • Universitatsklinikum Dusseldorf
  • Essen, Germany
    • Recruiting
    • Kliniken Essen-Mitte
  • Essen, Germany
    • Recruiting
    • Universitätsklinikum Essen
  • Freiburg, Germany
    • Recruiting
    • Universitätsklinikum Freiburg
  • Göttingen, Germany
    • Recruiting
    • Universitätsmedizin Göttingen
  • Hamburg, Germany
    • Recruiting
    • Universitätsklinikum Hamburg-Eppendorf
  • Hannover, Germany
    • Recruiting
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany
    • Recruiting
    • Universitätsklinium Heidelberg
  • Kiel, Germany
    • Recruiting
    • Universitätsklinikum Schleswig-Holstein, Campus Kiel
  • Köln, Germany
    • Recruiting
    • Uniklinikum Köln
  • Leipzig, Germany
    • Not yet recruiting
    • Universitätsklinikum Leipzig
  • München, Germany
    • Recruiting
    • Technische Universität München
  • Regensburg, Germany
    • Recruiting
    • Universitat Regensburg
  • Stuttgart, Germany
    • Recruiting
    • Interdisziplinäres Brustzentrum am Diakonieklinikum
  • Tübingen, Germany
    • Recruiting
    • Universitätsklinikum Tübingen
  • Ulm, Germany
    • Recruiting
    • Universität Ulm
  • Würzburg, Germany
    • Recruiting
    • Universitätsklinikum Würzburg

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• proven pathogenic BRCA1/2 mutation
• age >=18
• written informed consent

Exclusion Criteria:

• current chemotherapy of radiotherapy (inclusion 6 weeks after CTX or RX possible)
• metastatic tumor disease
• life expectancy <3 years
• clinically limiting cardiovascular or respiratory disease (instable CVD, heart failure stage IV, COPD GOLD IV, maximum resting blood pressure 160/100 mmHg)
• significant orthopedic disability which prevents from participating in the group interventions
• severe concomitant diseases which prevents from participating in the group interventions
• Karnofsky index <60
• maximum exercise capacity <50 W
• food allergies which prevent from mediterranean diet
• vegan diet
• body mass index <15 kg/m2
• pregnancy
• insufficient knowledge of German language
• insufficient compliance
• active participation in other interventional trials

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Study participants are instructed regarding a healthy diet according to the recommendations of the German Nutrition Society (DGE) and are informed about positive effects of physical activity on incidence and prognosis of breast cancer
Experimental: Intervention; Structured exercise training plus mediterranean diet: Study participants receive a lifestyle intervention of 12 months duration (3 months intensive intervention plus 9 months maintenance using monthly contacts and meetings). The intervention comprises a structured intensified training based on the results of physical performance diagnostics and a nutrition program based on a mediterranean diet.	Behavioral: Structured exercise training plus mediterranean diet; Structured exercise training plus mediterranean diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mediterranean Diet Adherence Screener (MEDAS) Score (Questionnaire)	Adherence to mediterranean diet	12 months
body mass index (BMI)	Body weight (in kilograms) divided by body height (in meters) squared.	12 months
ventilatory threshold 1 (VT1) in spiroergometry	ventilatory threshold VT1 in spiroergometry	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
stress coping capacity, as measured by the Trier Inventory for Chronic Stress (TICS) questionnaire	(TICS) questionnaire	3, 12, 24, 36 months
grade of optimism, as measured by the Life Orientation Test (LOT) questionnaire	Life Orientation Test (LOT)	3, 12, 24, 36 months
attitudes and beliefs regarding physical training and healthy diet, as measured by the "Bewertung körperlicher Aktivität und Ernährung" (BKAE) questionnaire	(BKAE) questionnaire	3, 12, 24, 36 months
quality of life, as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)	(EORTC QLQ-C30)	3, 12, 24, 36 months
maximum oxygen consumption (VO2max), as measured by spiroergometry	spiroergometry	3, 12 months
physical activity, as measured by the International Physical Activity Questionnaire (IPAQ)	Physical Activity	3, 12, 24, 36 months
incidence of breast cancer	During study	12, 24, 36 months
Mediterranean Diet Adherence Screener (MEDAS) Score	(MEDAS) Score	3, 6, 9, 12, 24, 36 months
body mass index (BMI)	(BMI)	3, 12, 24, 36 months
change of maximum oxygen consumption (VO2max) at ventilation threshold 1 (VT1), as measured by spiroergometry	spiroergometry	3, 12 months
mortality rate	During study	12, 24, 36 months
satisfaction (questionnaire)	satisfaction (questionnaire)	3, 12, 24, 36 months
tobacco consumption	survey	12, 24, 36 months
alcohol consumption	survey	12, 24, 36 months
dietary habits and calory intake, as measured by the European Prospective Investigation into Cancer and Nutrition Study Food Frequency Questionnaire (EPIC-FFQ)	(EPIC-FFQ)	3, 12, 24, 36 months
serum cholesterol, serum high density lipoprotein cholesterol,serum, serum Glucose, triglycerides, c-reactive Protein, serum Insulin,proneurotensin	Blood Test	3, 12, 24, 36 months
proenkephalin	Genetic test	3, 12, 24, 36 months
Omega 3 fatty acid in the erythrocyte Membrane, Omega 6 fatty acid level in the erythrocyte Membraserum low density, lipoprotein cholesterolne, Omega 9 fatty acid level in the erythrocyte Membrane,	Blood Test	3, 12, 24, 36 months

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Collaborators: University of Cologne; University of Leipzig; University Hospital Schleswig-Holstein; University of Hohenheim
• Investigators: Study Director: Marion Kiechle, Prof. Dr., Technical University of Munich; Study Director: Martin Halle, Prof. Dr., Technical University of Munich; Study Director: Stephan C Bischoff, Prof. Dr., Universitaet Hohenheim, Stuttgart; Study Director: Michael Siniatchkin, Prof. Dr., Universitätsklinikum Schleswig-Holstein, Campus Kiel; Study Director: Markus Loeffler, Prof. Dr., University of Leipzig; Study Director: Christoph Engel, PD Dr., University of Leipzig; Study Director: Rita K Schmutzler, Prof. Dr., University of Cologne; Study Director: Alfons Meindl, Prof. Dr., Technical University of Munich; Principal Investigator: Anne S Quante, Dr., Technical University of Munich

Publications and helpful links

General Publications

• Seethaler B, Nguyen NK, Basrai M, Kiechle M, Walter J, Delzenne NM, Bischoff SC. Short-chain fatty acids are key mediators of the favorable effects of the Mediterranean diet on intestinal barrier integrity: data from the randomized controlled LIBRE trial. Am J Clin Nutr. 2022 Oct 6;116(4):928-942. doi: 10.1093/ajcn/nqac175.
• Kiechle M, Engel C, Berling A, Hebestreit K, Bischoff SC, Dukatz R, Siniatchkin M, Pfeifer K, Grill S, Yahiaoui-Doktor M, Kirsch E, Niederberger U, Enders U, Loffler M, Meindl A, Rhiem K, Schmutzler R, Erickson N, Halle M. Effects of lifestyle intervention in BRCA1/2 mutation carriers on nutrition, BMI, and physical fitness (LIBRE study): study protocol for a randomized controlled trial. Trials. 2016 Jul 29;17:368. doi: 10.1186/s13063-016-1504-0.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: July 22, 2015
• First Submitted That Met QC Criteria: August 3, 2015
• First Posted (Estimated): August 6, 2015

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: prevention; Mediterranean diet; hereditary breast and ovarian cancer (HBOC); BRCA1/2 mutation carriers; Structured exercise training
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Breast Diseases; Genetic Diseases, Inborn; Neoplastic Syndromes, Hereditary; Breast Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Ovarian Neoplasms; Hereditary Breast and Ovarian Cancer Syndrome
• Other Study ID Numbers: LIBRE-2-20150626