We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Nutrition and Energy Restriction for Cancer Prevention (HELENA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02449148
Recruitment Status : Completed
First Posted : May 20, 2015
Last Update Posted : January 13, 2022
Sponsor:
Collaborator:
University Hospital Heidelberg
Information provided by (Responsible Party):
Tilman Kuehn, German Cancer Research Center

Tracking Information
First Submitted Date  ICMJE April 1, 2015
First Posted Date  ICMJE May 20, 2015
Last Update Posted Date January 13, 2022
Study Start Date  ICMJE May 2015
Actual Primary Completion Date May 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2015)
Changes in gene expression in subcutaneous adipose tissue measured by whole genome sequencing [ Time Frame: Assessments at baseline (week 0), and after the intervention phase (week 13) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 27, 2021)
  • Changes in abdominal fat distribution pattern (visceral, subcutaneous, total adipose tissue) measured by magnetic resonance spectroscopy [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13),and after the follow-up phase (week 52) ]
  • Changes in blood-based biomarkers, i.e. parameters of inflammation, adipokines, growth and hormonal factors, which have been shown to be associated with obesity-related chronic diseases before [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintenance phase (week 25), and after the maintenance phase (week 25) ]
  • Changes in weight (kg) [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintencance phase (week 25) and after the follow-up phase (week 52) ]
  • Changes in BMI (kg/m2) [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintencance phase (week 25) and after the follow-up phase (week 52) ]
  • Changes in waist circumference (cm) [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintencance phase (week 25) and after the follow-up phase (week 52) ]
  • Changes in hip circumference (cm) [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintencance phase (week 25) and after the follow-up phase (week 52) ]
  • Changes in blood pressure (mm/Hg) [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintencance phase (week 25) and after the follow-up phase (week 52) ]
  • Changes in pulse (bpm) [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintencance phase (week 25) and after the follow-up phase (week 52) ]
  • Changes in quality of life (as defined by changes in SF-12-derived scores) [ Time Frame: Assessments at baseline (week 0) and after the intervention phase (week 13) ]
  • Changes in liver fat content measured by magnetic resonance spectroscopy [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13),and after the follow-up phase (week 52) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2015)
  • Changes in abdominal fat distribution pattern (visceral, subcutaneous, total adipose tissue) measured by magnetic resonance spectroscopy [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13),and after the follow-up phase (week 52) ]
  • Changes in blood-based biomarkers, i.e. parameters of inflammation, adipokines, growth and hormonal factors, which have been shown to be associated with obesity-related chronic diseases before [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintenance phase (week 25), and after the maintenance phase (week 25) ]
  • Changes in the composition of the gut microbiota by taxonomic, functional, and comparative analysis of sequencing data [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), and after the maintenance phase (week 25) ]
  • Changes in blood, leucocyte and urine metabolites, as measured by LC-MS/MS based targeted and untargeted metabolomics tools [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintencance phase (week 25) and after the follow-up phase (week 52) ]
  • Changes in weight (kg) [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintencance phase (week 25) and after the follow-up phase (week 52) ]
  • Changes in BMI (kg/m2) [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintencance phase (week 25) and after the follow-up phase (week 52) ]
  • Changes in waist circumference (cm) [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintencance phase (week 25) and after the follow-up phase (week 52) ]
  • Changes in hip circumference (cm) [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintencance phase (week 25) and after the follow-up phase (week 52) ]
  • Changes in blood pressure (mm/Hg) [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintencance phase (week 25) and after the follow-up phase (week 52) ]
  • Changes in pulse (bpm) [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintencance phase (week 25) and after the follow-up phase (week 52) ]
  • Changes in quality of life (as defined by changes in SF-12-derived scores) [ Time Frame: Assessments at baseline (week 0) and after the intervention phase (week 13) ]
  • Changes in liver fat content measured by magnetic resonance spectroscopy [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13),and after the follow-up phase (week 52) ]
Current Other Pre-specified Outcome Measures
 (submitted: December 27, 2021)
  • Changes in the composition of the gut microbiota by taxonomic, functional, and comparative analysis of sequencing data [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintencance phase (week 25) and after the follow-up phase (week 52) ]
    Exploratory Outcome
  • Changes in blood metabolites, as measured by LC-MS/MS-based targeted and untargeted metabolomics tools [ Time Frame: Assessments at baseline (week 0), after the intervention phase (week 13), after the maintencance phase (week 25) and after the follow-up phase (week 52) ]
    Exploratory Outcome
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nutrition and Energy Restriction for Cancer Prevention
Official Title  ICMJE Healthy Nutrition and Energy Restriction as Cancer Prevention Strategies: a Randomized Controlled Intervention Trial
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Obesity
  • Visceral Obesity
  • Weight Loss
  • Metabolic Diseases
  • Body Composition, Beneficial
Intervention  ICMJE Other: Calorie Restriction
diet intervention to reduce the risk for obesity associated diseases
Other Name: weight loss trial;
Study Arms  ICMJE
  • Experimental: Intermittent Calorie Restriction
    2 days per week fasting with 25 % energy intake and 5 days per week at 100% energy intake
    Intervention: Other: Calorie Restriction
  • Experimental: Continuous Calorie Restriction
    daily energy intake of 80 %
    Intervention: Other: Calorie Restriction
  • No Intervention: Healthy Nutrition
    general advice on healthy nutrition
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 15, 2015)
150
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 2017
Actual Primary Completion Date May 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Women and men aged 35 to 65 years
  • Overweight or obese (BMI ≥ 25 kg/m2 ≤ 40 kg/m2 )
  • German speaking
  • Non- smoker
  • Provision of written informed consent

Exclusion Criteria:

  • Not able to understand and sign the informed consent form in person
  • Already diagnosed diabetes
  • HbA1c ≥ 6.5 % and/or fasting plasma glucose > 125 mg/dl
  • History of cancer within the past 10 years
  • Risk of bleeding disorders (e.g. Marcumar intake)
  • Current or history of eating disorders (bulimia, anorexia, binge-eating)
  • Pregnant or lactating during the past 12 months
  • Increased or decreased thyroid-stimulating hormone in baseline blood check
  • Already diagnosed hepatic dysfunction and/or increased or decreased γ-GT, GPT and/or GOT in baseline blood check
  • Already diagnosed kidney dysfunction and/or increased or decreased creatinine, urea and/or uric acid in baseline blood check
  • Medications that might affect the endpoints of the study e.g. immunosuppressive medication (cortisol, antibody treatment), hormone replacement therapy, medication for fat metabolism (e.g. statine, fibrate)
  • Participation in another intervention study shorter than three months ago
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02449148
Other Study ID Numbers  ICMJE DKFZ Study_ID 670
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Tilman Kuehn, German Cancer Research Center
Original Responsible Party Same as current
Current Study Sponsor  ICMJE German Cancer Research Center
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE University Hospital Heidelberg
Investigators  ICMJE
Principal Investigator: Tilman Kühn, PhD German Cancer Research Center
PRS Account German Cancer Research Center
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP