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

• ClinicalTrials.gov Identifier: NCT02516540
• Recruitment Status: Recruiting
• First Posted: August 6, 2015
• Last Update Posted: October 26, 2022
• Sponsor: Technical University of Munich
• Collaborators: University of Hohenheim; University Hospital Schleswig-Holstein; University of Leipzig; University of Cologne
• Information provided by (Responsible Party): Technical University of Munich

Tracking Information

• First Submitted Date: July 22, 2015
• First Posted Date: August 6, 2015
• Last Update Posted Date: October 26, 2022
• Actual Study Start Date: March 2015
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 10, 2021)

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

Original Primary Outcome Measures (submitted: August 3, 2015)

• Mediterranean Diet Adherence Screener (MEDAS) Score (Questionnaire) [ Time Frame: 12 months ]
  Adherence to mediterranean diet
• body mass index (BMI) [ Time Frame: 12 months ]
• ventilatory threshold 1 (VT1) in spiroergometry [ Time Frame: 12 months ]
  ventilatory threshold VT1 in spiroergometry

Current Secondary Outcome Measures (submitted: April 10, 2021)

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

Original Secondary Outcome Measures (submitted: August 3, 2015)

• stress coping capacity, as measured by the Trier Inventory for Chronic Stress (TICS) questionnaire [ Time Frame: 3, 12, 24, 36 months ]
• grade of optimism, as measured by the Life Orientation Test (LOT) questionnaire [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 3, 12, 24, 36 months ]
• maximum oxygen consumption (VO2max), as measured by spiroergometry [ Time Frame: 3, 12 months ]
• physical activity, as measured by the International Physical Activity Questionnaire (IPAQ) [ Time Frame: 3, 12, 24, 36 months ]
• incidence of breast cancer [ Time Frame: 12, 24, 36 months ]
• Mediterranean Diet Adherence Screener (MEDAS) Score [ Time Frame: 3, 6, 9, 12, 24, 36 months ]
• body mass index (BMI) [ Time Frame: 3, 12, 24, 36 months ]
• change of maximum oxygen consumption (VO2max) at ventilation threshold 1 (VT1), as measured by spiroergometry [ Time Frame: 3, 12 months ]
• mortality rate [ Time Frame: 12, 24, 36 months ]
• satisfaction (questionnaire) [ Time Frame: 3, 12, 24, 36 months ]
• tobacco consumption [ Time Frame: 12, 24, 36 months ]
• alcohol consumption [ Time Frame: 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) [ Time Frame: 3, 12, 24, 36 months ]
• Omega 3 fatty acid in the erythrocyte membrane [ Time Frame: 3, 12, 24, 36 months ]
• Omega 6 fatty acid level in the erythrocyte membrane [ Time Frame: 3, 12, 24, 36 months ]
• Omega 9 fatty acid level in the erythrocyte membrane [ Time Frame: 3, 12, 24, 36 months ]
• serum cholesterol [ Time Frame: 3, 12, 24, 36 months ]
• serum high density lipoprotein cholesterol [ Time Frame: 3, 12, 24, 36 months ]
• serum low density lipoprotein cholesterol [ Time Frame: 3, 12, 24, 36 months ]
• serum triglycerides [ Time Frame: 3, 12, 24, 36 months ]
• serum glucose [ Time Frame: 3, 12, 24, 36 months ]
• c-reactive protein [ Time Frame: 3, 12, 24, 36 months ]
• serum insulin [ Time Frame: 3, 12, 24, 36 months ]
• body fat content, as measured by skin folds measurement [ Time Frame: 3, 12, 24, 36 months ]
• proenkephalin [ Time Frame: 3, 12, 24, 36 months ]
• proneurotensin [ Time Frame: 3, 12, 24, 36 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
• Official Title: Prospective Randomized Multicenter Trial to Assess the Efficacy of a Structured Physical Exercise Training and Mediterranean Diet in Women With BRCA1/2 Mutations
• Brief Summary: 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.
• 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
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Hereditary Breast and Ovarian Cancer

Intervention

Behavioral: Structured exercise training plus mediterranean diet

Structured exercise training plus mediterranean diet

Study Arms

• 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.
  Intervention: Behavioral: Structured exercise training plus mediterranean diet

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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 3, 2015): 600
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2025
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Marion Kiechle, Prof. Dr.; +49 89 4140 2420; marion.kiechle@tum.de

Contact: Daniela Schemmer; +49 89 4140 2433; Daniela.Schemmer@mri.tum.de

• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT02516540
• Other Study ID Numbers: LIBRE-2-20150626
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Technical University of Munich
• Original Responsible Party: Same as current
• Current Study Sponsor: Technical University of Munich
• Original Study Sponsor: Same as current

Collaborators

• University of Hohenheim
• University Hospital Schleswig-Holstein
• University of Leipzig
• University of Cologne

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

• PRS Account: Technical University of Munich
• Verification Date: October 2022