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A Case Crossover Study of Intermittent Fasting in CLL/SLL

Primary Purpose

Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)

Status
Active
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
5:2 Method (intermittent fasting regimen)
16/8 Method (intermittent fast regimen)
Sponsored by
British Columbia Cancer Agency
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Chronic Lymphocytic Leukemia (CLL) focused on measuring diet, nutrition, intermittent fasting, time restricted feeding, oncology, autophagy, metabolomics

Eligibility Criteria

19 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Diagnosis of CLL or SLL Age < 85 years Peripheral blood lymphocytes >20 x 109/L Hemoglobin > 90g/L Platelets > 90 x 10*9/L BMI of >=20kg/m2 ECOG Performance Status >=2 Completion of "IF in CLL/SLL Study" (ClinicalTrials.gov Identifier: NCT04626843) followed by minimum of 3 month ad libitum eating Exclusion Criteria: Patient unable to give consent Patient on medications required to be taken with food during the fasting window Pregnancy Diabetes mellitus BMI drop to < 18.5kg/m2 at any time during study Anti-lymphoma therapy within the past 3 months Expected to require initiation of anti-lymphoma therapy within the next 3 months

Sites / Locations

  • Eleah Stringer

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

5:2 Method

16/8 Method

Arm Description

Participants will follow the 5:2 Method (an intermittent fasting regimen) for a 90 day duration. This entails eating ad libitum for five days per week ("normal days") and limiting total calorie intake to 800kcals per day ("fasting days") for the remaining two days per week. The fasting days can be sequential or dispersed throughout the week, based on patient preference.

Participants will have already followed the 16/8 Method (an intermittent fasting regimen) for a minimum of six days per week for a 90 day duration. This entailed limiting the eating hours to an 8-hour window, then fasting for the remaining 16 hours per day, with the last time of intake being 8pm.

Outcomes

Primary Outcome Measures

Change in lymphocyte count [ Time Frame: Within 3 months pre-intervention, monthly during intervention, 1 month post-intervention ]
Changes in lymphocyte count will be measured between each peripheral blood draw and also compared to the former results as part of the "IF in CLL/SLL Study" (ClinicalTrials.gov Identifier: NCT04626843).
Change in inflammation
Changes in c-reactive protein (CRP) will be measured between each peripheral blood draw and also compared to the former results as part of the "IF in CLL/SLL Study" (ClinicalTrials.gov Identifier: NCT04626843).
Change in metabolomic profiles (optional)
Changes in abundance of stool metabolites will be measured between each stool sample and between the two interventional arms. This includes, but is not limited to, an established short-chain fatty acid and bile acid panel that analyzes 77 and 10 unique metabolites, respectively.
Change in autophagy status
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.
Changes in immune cell gene expression profiles
Changes in expression profiles of selected immune cell genes

Secondary Outcome Measures

Change in gut microbiome (optional)
Stool samples to identify baseline and fasting-induced changes in abundance and repertoire of the gut microbiota.

Full Information

First Posted
December 21, 2022
Last Updated
June 21, 2023
Sponsor
British Columbia Cancer Agency
Collaborators
BC Cancer Foundation, University of Victoria
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1. Study Identification

Unique Protocol Identification Number
NCT05708326
Brief Title
A Case Crossover Study of Intermittent Fasting in CLL/SLL
Official Title
Does Timing Matter? A Case Crossover Study of Intermittent Fasting in Patients With CLL/SLL at BC Cancer- Victoria
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 12, 2023 (Actual)
Primary Completion Date
September 30, 2023 (Anticipated)
Study Completion Date
December 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
British Columbia Cancer Agency
Collaborators
BC Cancer Foundation, University of Victoria

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to compare the 16/8 intermittent fasting method with the 5:2 Method in a subset of patients with chronic lymphocytic leukemia or small lymphocytic lymphoma at BC Cancer- Victoria. The purpose is to find out which is the preferred method by patients and which has the greatest effect on: cancer cells (lymphyocyte count), metabolism (autophagy activation), inflammation (CRP), gut microbiome (metabolomic analysis). Participants will have already completed our previous trial, "Intermittent Fasting in CLL/SLL" (ClinicalTrials.gov Identifier: NCT04626843) where they followed the 16/8 Fasting Method followed by a minimum of a 3 months washout period, and will now follow the 5:2 Method for 90 days. The same samples and outcome measures will be collected in order to directly compare the two diets in the same patient cohort.
Detailed Description
BACKGROUND: Interest in intermittent fasting (IF) is growing rapidly for its potential to improve health outcomes. IF is a diet regime that cycles between fasting and eating for a defined period. There are many variations of IF, most altering the length of the fasting window but some may include caloric restriction. The investigators are nearing completion a feasibility study on the effects of IF on chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) at BC Cancer- Victoria. This clinical trial, "IF in CLL/SLL" (ClinicalTrials.gov Identifier: NCT04626843) investigates the biochemical effects of the 16/8 Method on CLL/SLL tumor control, markers of inflammation, and autophagy induction in a case-controlled study. Preliminary findings demonstrate excellent compliance and early feedback and findings are overwhelmingly positive. It is unknown, however, how the 16/8 Method compares to other IF regimens in terms of patient acceptability and biologic effects. OBJECTIVE: The aim is to examine the two most common regimens, the 16/8 Method (16 hr fast) and the 5:2 Method (2 day per week of caloric restriction of 800 kcals). The primary research questions are, which IF strategy has the greatest effect on, (1) tumour burden (lymphocyte count), (2) autophagy induction and gut microbiome composition, (3) inflammation, (4) and is preferred by patients. METHODS: This study is an extension of the investigators' current, single-arm trial to expand to a case crossover design, allowing each participant to serve as their own control. Following completion of a 90 day trial on the 16/8 Method during the "Intermittent Fasting in CLL/SLL" study (ClinicalTrials.gov Identifier: NCT04626843) and following a minimum of a 3 month washout period, participants will now follow the 5:2 Method for 90 days. Data collection will match previous current study protocol to allow for statistical comparison between lymphocyte count, inflammation, metabolomic profiles, autophagy status, and the gut microbiome (optional). Participants will complete a semi-structured interview on their experiences with the 16/8 Method and 5:2 Method that will be qualitatively analyzed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
Keywords
diet, nutrition, intermittent fasting, time restricted feeding, oncology, autophagy, metabolomics

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Participants will have previously completed the first arm (trial of the 16/8 intermittent fasting method), and are now invited to the second arm (the 5:2 Method), serving as their own control.
Masking
Outcomes Assessor
Allocation
Non-Randomized
Enrollment
8 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
5:2 Method
Arm Type
Experimental
Arm Description
Participants will follow the 5:2 Method (an intermittent fasting regimen) for a 90 day duration. This entails eating ad libitum for five days per week ("normal days") and limiting total calorie intake to 800kcals per day ("fasting days") for the remaining two days per week. The fasting days can be sequential or dispersed throughout the week, based on patient preference.
Arm Title
16/8 Method
Arm Type
Active Comparator
Arm Description
Participants will have already followed the 16/8 Method (an intermittent fasting regimen) for a minimum of six days per week for a 90 day duration. This entailed limiting the eating hours to an 8-hour window, then fasting for the remaining 16 hours per day, with the last time of intake being 8pm.
Intervention Type
Behavioral
Intervention Name(s)
5:2 Method (intermittent fasting regimen)
Intervention Description
Participants will follow the 5:2 Method (an intermittent fasting regimen) for a 90 day duration. This entails eating ad libitum for five days per week ("normal days") and limiting total calorie intake to 800kcals per day ("fasting days") for the remaining two days per week. The fasting days can be sequential or dispersed throughout the week, based on patient preference.
Intervention Type
Behavioral
Intervention Name(s)
16/8 Method (intermittent fast regimen)
Intervention Description
Participants will have already followed the 16/8 Method (an intermittent fasting regimen) for a minimum of six days per week for a 90 day duration. This entailed limiting the eating hours to an 8-hour window, then fasting for the remaining 16 hours per day, with the last time of intake being 8pm.
Primary Outcome Measure Information:
Title
Change in lymphocyte count [ Time Frame: Within 3 months pre-intervention, monthly during intervention, 1 month post-intervention ]
Description
Changes in lymphocyte count will be measured between each peripheral blood draw and also compared to the former results as part of the "IF in CLL/SLL Study" (ClinicalTrials.gov Identifier: NCT04626843).
Time Frame
Within 3 months pre-intervention, monthly during intervention, 1 month post-intervention
Title
Change in inflammation
Description
Changes in c-reactive protein (CRP) will be measured between each peripheral blood draw and also compared to the former results as part of the "IF in CLL/SLL Study" (ClinicalTrials.gov Identifier: NCT04626843).
Time Frame
Within 3 months pre-intervention, monthly during intervention, 1 month post-intervention
Title
Change in metabolomic profiles (optional)
Description
Changes in abundance of stool metabolites will be measured between each stool sample and between the two interventional arms. This includes, but is not limited to, an established short-chain fatty acid and bile acid panel that analyzes 77 and 10 unique metabolites, respectively.
Time Frame
Day 1 (start/baseline) and day 90 (end/final) of intervention
Title
Change in autophagy status
Description
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.
Time Frame
Time Frame: Within 3 months pre-intervention, monthly during intervention, 1 month post-intervention
Title
Changes in immune cell gene expression profiles
Description
Changes in expression profiles of selected immune cell genes
Time Frame
Time Frame: Within 3 months pre-intervention, monthly during intervention, 1 month post-intervention
Secondary Outcome Measure Information:
Title
Change in gut microbiome (optional)
Description
Stool samples to identify baseline and fasting-induced changes in abundance and repertoire of the gut microbiota.
Time Frame
Day 1 (start/baseline) and day 90 (end/final) of intervention

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of CLL or SLL Age < 85 years Peripheral blood lymphocytes >20 x 109/L Hemoglobin > 90g/L Platelets > 90 x 10*9/L BMI of >=20kg/m2 ECOG Performance Status >=2 Completion of "IF in CLL/SLL Study" (ClinicalTrials.gov Identifier: NCT04626843) followed by minimum of 3 month ad libitum eating Exclusion Criteria: Patient unable to give consent Patient on medications required to be taken with food during the fasting window Pregnancy Diabetes mellitus BMI drop to < 18.5kg/m2 at any time during study Anti-lymphoma therapy within the past 3 months Expected to require initiation of anti-lymphoma therapy within the next 3 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicol Macpherson, MD, PhD, FRCPC
Organizational Affiliation
BC Cancer and University of British Columbia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Eleah Stringer
City
Victoria
State/Province
British Columbia
ZIP/Postal Code
V8R 6V5
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35639262
Citation
Stringer E, Lum JJ, Macpherson N. Intermittent Fasting in Cancer: a Role in Survivorship? Curr Nutr Rep. 2022 Sep;11(3):500-507. doi: 10.1007/s13668-022-00425-0. Epub 2022 May 31.
Results Reference
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A Case Crossover Study of Intermittent Fasting in CLL/SLL

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