Nutrition and Energy Restriction for Cancer Prevention
Condition: Obesity; Visceral Obesity; Weight Loss; Metabolic Diseases; Body Composition, Beneficial
MeSH terms: Obesity; Metabolic Diseases; Obesity, Abdominal; Weight Loss
Study type: Interventional

Summary: 
      This study evaluates the effect of intermittent calorie restriction versus continued calorie
      restriction on weight loss, gene expression profile of subcutaneous adipose tissue and
      abdominal fat distribution.
    

Detailed description: 
      Since obesity has become a major public health concern appropriate strategies are needed in
      order to reduce obesity-related health risks in later life span. Obesity is one of the main
      risk factors not only for diabetes and cardiovascular diseases, but also for several types of
      cancer. Several key mechanisms, which may link obesity, metabolic dysregulation and cancer
      risk, such as obesity-driven inflammation, altered adipokine, growth factor and sex hormone
      signaling, and changes in the microbiota have been identified.

      Various studies have shown that continuous calorie restriction (CCR) and exercise are
      effective strategies to enforce weight-loss and improve biomarker profiles. Intermittent
      calorie restriction (ICR) as a novel strategy might induce favorable metabolic changes and
      lead to higher compliance rates. The concept of this diet regime is very simple e.g. 2
      days/week of fasting following a standardized diet covering 25 % of energy needs and 5
      days/week of ad libitum consumption. To verify the effectiveness of ICR as an alternative
      weight loss strategy to CCR controlled intervention trials are required. Although both CCR
      and ICR induce a negative energy balance, the metabolic effect on human physiology might
      differ.

      Within the HELENA-study 50 non-smoking adults (men and women aged 35 to 65 years) with an BMI
      ≥ 25 kg/m² and ≤ 40 kg/m² will be randomly assigned to each of the intervention arms: (1) ICR
      arm (2 day/week fasting, i.e. 25% energy intake, energy intake of 100% on 5 days/week leading
      to a weekly average energy intake of ~80%) (2) CCR arm (daily energy intake of 80%) and 3)
      control arm (general advice on healthy nutrition).

      The trial will last 1 year, with an intervention phase of 12 weeks (weeks 0-12; intervention;
      close contact with participants), followed by a maintenance phase (weeks 13-24; maintenance;
      regular, but less frequent contact with participants) and a follow-up phase (weeks 25-52).

      Biological specimens will be collected as follows:

      Baseline (T0, week 1): Blood, urine, stool and subcutaneous adipose tissue samples; After 3
      months (T1, week 13): Blood, urine, stool and subcutaneous adipose tissue samples; After 6
      months (T2, week 25): Blood, urine, and stool; After 12 months (T3, week 52): Blood and
      urine; Magnet resonance tomography imaging (MRI, at T0, T1 and T3) and lifestyle assessments
      (nutrition behavior, physical activity and quality of life, T0-T3) will be performed to
      unravel the link to fat distribution, metabolic changes, health and lifestyle. The primary
      objective of the three-arm randomized controlled intervention trial is to investigate the
      effect of nutrition intervention on body weight and gene expression profile in subcutaneous
      adipose tissue of overweight and obese individuals. We hypothesize that better compliance
      rates will be achieved by the ICR rather than by the CCR group and that ICR will show a
      higher sustainability with respect to weight loss, weight maintenance, and biomarker
      profiles. The purpose of this study is further to analyze if the nutrition interventions and
      associated weight loss have different effects on abdominal fat distribution and liver fat
      content.

      The statistical analysis will be carried out by using the SAS statistical software [SAS
      Institute Inc., Cary, NC, USA] or comparable software. Descriptive statistics, correlations
      and univariate analyses will be used to get insight on general characteristics of
      participants in the intervention groups. For the primary objective, two sided t-test and
      ANCOVA modelling will be performed to investigate whether changes in gene expression levels
      are affected by nutrition intervention. Comparisons between two groups (e.g. ICR and CCR or
      CCR/ICR and control group) will be carried out using t-tests and parallel comparison across
      the three groups will be carried out using ANCOVA models. Where applicable, the analyses will
      include adjustments for confounders, specially age and gender. Likewise, stratified analysis
      will be carried out as necessary. ANCOVA models will be performed to evaluate the effects of
      nutrition intervention on biomarker profiles, adjusted by strata age and gender. Similar
      evaluations will be performed for fat distribution patterns, quality of life, physical
      activity and nutrition patterns. In addition, correlation and linear regression analyses will
      be performed to measure effects of weight-loss, gene expression levels and metabolic
      profiles, controlled by nutrition intervention group.
    

Intervention name(s): Calorie Restriction
Intervention type(s): Other
Intervention description(s): diet intervention to reduce the risk for obesity associated diseases
Other intervention name(s): weight loss trial;
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: energy restriction; fasting; intermittent fast; cancer prevention; subcutaneous fat tissue gene expression