Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers

Study Overview
=================
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.

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

Conditions
-----------------
Hereditary Breast and Ovarian Cancer

Intervention / Treatment
-----------------
* Behavioral: Structured exercise training plus mediterranean diet


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>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<br>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<br>* Structured exercise training plus mediterranean diet<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hereditary breast and ovarian cancer (HBOC), BRCA1/2 mutation carriers, Mediterranean diet, Structured exercise training, prevention