A Case Crossover Study of Intermittent Fasting in CLL/SLL

NCT05708326 | Completed

• 1 other identifier: H21-02145
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

diet; nutrition; intermittent fasting; time restricted feeding; oncology; autophagy; metabolomics

Outcome Measures

Primary Outcomes (5)

• 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).

  Within 3 months pre-intervention, monthly during intervention, 1 month post-intervention

• 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).

  Within 3 months pre-intervention, monthly during intervention, 1 month post-intervention

• 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.

  Day 1 (start/baseline) and day 90 (end/final) of intervention

• 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.

  Time Frame: Within 3 months pre-intervention, monthly during intervention, 1 month post-intervention

• Changes in immune cell gene expression profiles

  Changes in expression profiles of selected immune cell genes

  Time Frame: Within 3 months pre-intervention, monthly during intervention, 1 month post-intervention

Secondary Outcomes (1)

• Change in gut microbiome (optional)

  Day 1 (start/baseline) and day 90 (end/final) of intervention

Study Arms (2)

5:2 Method

EXPERIMENTAL

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.

Behavioral: 5:2 Method (intermittent fasting regimen)

16/8 Method

ACTIVE COMPARATOR

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.

Behavioral: 16/8 Method (intermittent fast regimen)

Interventions

5:2 Method (intermittent fasting regimen) BEHAVIORAL

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.

5:2 Method

16/8 Method (intermittent fast regimen) BEHAVIORAL

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.

16/8 Method

Eligibility Criteria

• Age: 19 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• British Columbia Cancer Agency: lead
• BC Cancer Foundation: collaborator
• University of Victoria: collaborator

Study Sites (1)

Eleah Stringer

Victoria, British Columbia, V8R 6V5, Canada

Location

Related Publications (1)

• 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.

  PMID: 35639262 BACKGROUND

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Intermittent Fasting; Neoplasms

Interventions

Methods

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Fasting; Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Investigative Techniques

Study Officials

• Nicol Macpherson, MD, PhD, FRCPC

  BC Cancer and University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dietitian Investigator

Model Details: 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.

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: February 1, 2023
• Study Start: June 12, 2023
• Primary Completion: October 30, 2023
• Study Completion: December 30, 2023
• Last Updated: March 8, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)