Nutritional and Metabolic Diseases

All Conditions

Symptoms and General Pathology

Metabolic Diseases

Weight Loss

Obesity

Body Weight

Obesity, Abdominal

Overweight

Overnutrition

Nutrition Disorders

Body Weight Changes

2 days per week fasting with 25 % energy intake and 5 days per week at 100% energy intake

diet intervention to reduce the risk for obesity associated diseases

Calorie Restriction

Tilman Kühn, PhD

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.

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.

Nutrition and Energy Restriction for Cancer Prevention

Healthy Nutrition and Energy Restriction as Cancer Prevention Strategies: a Randomized Controlled Intervention Trial

University Hospital Heidelberg

German Cancer Research Center

Dr. Tilman Kühn

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Inflammation

Lymphoma

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

16/8 fasting method: fast for 16 hours of the day with an 8 hours feeding window for a duration of 3 months.

Intermittent fast

What are the investigators trying to do? By most measures, humans consume more food than needed. Over several decades, overconsumption has led to an increase in a number of diseases, including cancer. What if this could be reversed, or slowed down, by fasting? Would that improve how cancer patients respond to chemotherapy? Could simply changing eating patterns to reduce overall intake be a way to prevent and/or manage cancer? All of these are important questions and the investigators are undertaking a new initiative to study how nutrition and dietary behaviours affect cancer patients.

Fasting: A way to improve overall health and increase our defenses to cancer Fasting in various forms has been shown to have a number of health benefits. Intermittent fasting, or time restricted feeding, has been shown to reverse or improve various diseases such as diabetes, heart disease and metabolic syndrome, decrease the risk of cancer, and significantly extend the life of an individual. In previous studies, fasting was well-tolerated with notable improvements in energy levels, sense of well-being, and sleep quality. In cancer patients, clinical trials have demonstrated intermittent fasting to lessen some of the short-term side effects of chemotherapy such as nausea, fatigue, and sleep quality. How fasting alters the course of cancer or improve immune defenses is not yet known but may be an alternative way to treat or manage cancer.

The study plan The investigators plan to examine the effects of intermittent fasting (time restricted feeding) in patients with chronic lymphocytic leukemia (CLL). CLL is the most common chronic leukemia and is presently incurable. The advantage of choosing this patient population is that the cancer is easily assessed with a blood test measuring the amount of cancerous white cells (lymphocytes). Patients who consent to participate in this study will, through the support of an oncology dietitian and after a period of transition, split their daily feeding into a fasting period and a non-fasting period. This regime is as simple as skipping or having a late breakfast. At this time, participants will not be required to limit their total caloric intake.

What is required from the participant? The investigators will assess whether intermittent fasting reduces the cancer by measuring the lymphocyte count in the blood over a period of 3 months. Study participants will complete questionnaires to help determine if fasting causes any change in their quality of life. The effects of intermittent fasting on a cancer control system called autophagy, as well as its effects on inflammation will be studied in the Deeley Research Centre laboratory at BC Cancer.

What is the short- and long-term impact? In the short-term, if intermittent fasting can have an effect cancer lymphocyte count or on autophagy, then investigators will proceed with further studies to try and optimize the effects of intermittent fasting. In the long-term, this study is expected to be the first-ever to shed light on how intermittent fasting may be linked to cancer survival and/or growth. If true, this will open up new avenues to re-evaluate the inclusion of diet into cancer treatment protocols.

Intermittent Fasting and CLL/SLL

Feasibility Study of Intermittent Fasting in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (CLL/SLL) Patients at BC Cancer- Victoria

Changes in lymphocyte count will be measured between each peripheral blood draw.

A quality of life questionnaire, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Cancer 30 (EORTC QLQ-C30) version 3, will be administered to assess to subjective changes in well-being. It comprises 30 items (i.e. single questions), 24 of which are aggregated into nine multi-item scales, that is, five functioning scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and one global health status scale. The remaining six single-item scales assess symptoms. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the patient).

Changes in c-reactive protein (CRP) will be measured between each peripheral blood draw.

Changes in metabolomic profiles will be measured between each peripheral blood draw.

This includes standard flow cytometric analysis of lymphocyte subsets: a panel established by the Human Immunology Consortium Project as well as additional in-house markers to enumerate the frequency of lymphocytes before and at various time points post-treatment. The extent of autophagy will be tested by performing cytometry and western blotting assays using LC3II and p62 as readouts. Total cell counts in different lymphocyte subsets including, but not limited to, cluster of differentiation (CD) 3, CD8, CD4, CD20, CD19, and forkhead box P3 (FoxP3) will be assayed in conjugation with glucose uptake and mitochondrial function.

Expression profiles of selected immune cell genes

Stool samples to identify baseline and fasting-induced changes in abundance and repertoire of the gut microbiota

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nutrition and Energy Restriction for Cancer Prevention	NCT02449148	Obesity Visceral Obesit... Weight Loss Metabolic Disea... Body Compositio...	Calorie Restric...	35 Years - 65 Years	German Cancer Research Center
Intermittent Fasting and CLL/SLL	NCT04626843	Neoplasms Leukemia, Lymph... Lymphoma, Small... Intermittent Fa... Diet Habit Inflammation	Intermittent fa...	19 Years - 85 Years	British Columbia Cancer Agency
Intermittent Fasting and CLL/SLL	NCT04626843	Neoplasms Leukemia, Lymph... Lymphoma, Small... Intermittent Fa... Diet Habit Inflammation	Intermittent fa...	19 Years - 85 Years	British Columbia Cancer Agency

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