Clinical trial NCT05708326: 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
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Keywords: diet
nutrition
intermittent fasting
time restricted feeding
oncology
autophagy
metabolomics
Lead sponsor: British Columbia Cancer Agency
Sponsor class: OTHER
Collaborators: name: BC Cancer Foundation
name: University of Victoria
First posted: 2023-02-01
Enrollment: 6
Sex: ALL
Minimum age (years): 19
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Change in lymphocyte count [ Time Frame: Within 3 months pre-intervention, monthly during intervention, 1 month post-intervention ]
timeFrame: Within 3 months pre-intervention, monthly during intervention, 1 month post-intervention
measure: Change in inflammation
timeFrame: Within 3 months pre-intervention, monthly during intervention, 1 month post-intervention
measure: Change in metabolomic profiles (optional)
timeFrame: Day 1 (start/baseline) and day 90 (end/final) of intervention
measure: Change in autophagy status
timeFrame: Time Frame: Within 3 months pre-intervention, monthly during intervention, 1 month post-intervention
measure: Changes in immune cell gene expression profiles
timeFrame: Time Frame: Within 3 months pre-intervention, monthly during intervention, 1 month post-intervention
Secondary outcomes:
measure: Change in gut microbiome (optional)
timeFrame: Day 1 (start/baseline) and day 90 (end/final) of intervention
Other outcomes:
Locations:
city: Victoria
country: Canada
facility: Eleah Stringer
state: British Columbia
Study officials:
affiliation: BC Cancer and University of British Columbia
name: Nicol Macpherson, MD, PhD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
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.