The Effect of a Fasting MimickINg Diet on the Immune System (FIND)

The Effect of a Fasting MimickINg Diet on the Immune System: an Exploratory Study

Fasting or a Fasting Mimicking diet (FMD) can lower blood concentration of glucose and IGF1. Since cancer cells rely mostly on a glucose-based metabolism, FMD renders cancer cells more vulnerable to chemotherapy, thereby enhancing therapeutic efficacy. This process is known as differential stress sensitization (DSS). Another response to nutritional stress by fasting is known as differential stress resistance (DSR). DSR is a state in which healthy cells rather focus resources on protection and internal repair, which can result in reduced chemotherapeutic toxicity. Recent preclinical studies found that fasting or FMD not only aids healthy cell protection, but also has the potential to benefit effector T-cells and could thereby improve antitumor immunity. However in most oncotherapeutic clinical trials investigating the addition of a fasting regimen, other factors such as chemotherapy, surgery and additional medication affect the immune system as well. That is why this explorative study, conducted in healthy subjects, might be more suitable to investigate the immunological alterations upon FMD more specifically. This exploratory study aims to identify immunological alterations by using extensive immunoprofiling before and after three days of FMD in healthy subjects, as well as investigate possible side effects of FMD.

Study Overview

• Status: Completed
• Conditions: Neoplasms; Cancer; Healthy Subjects
• Intervention / Treatment: Other: Fasting Mimicking Diet

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands, 2333 ZA
      • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥18 years old
• BMI ≥18.5 and ≤25kg/m2

Exclusion Criteria:

• Chronic disease or active infection
• Medication use other than contraceptive, during the last 12 weeks prior to inclusion.
• A history of allergy
• Blood or plasma donation in the last 12 weeks prior to inclusion.
• Participation in other medical research in the last 12 weeks prior to inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fasting Mimicking Diet; 2 cycles of 3-day fasting mimicking spaced by a 2 week interval	Other: Fasting Mimicking Diet; Low-caloric, low-protein, plant-based diet regiment for 3 days; Other Names: Xentigen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in gene expression signature in peripheral blood mononuclear cells (PBMCs) after overnight fast and after completion of 2 cycles of fasting mimicking diet compared to baseline.	PBMCs are retrieved from whole blood samples. Gene expression signature is retrieved from PBMCs using RNA-Nanostring technique with the Pancancer IO 360 panel. The Nanostring will report RNA counts for a panel of 770 genes, including 40 housekeeping genes. The data will be normalized on the 40 housekeeping genes for internal control using Nanostring nSolver software. The fold change from baseline to overnight fast and after completion of second fasting mimicking diet will provide insight in affected pathways as well as metabolic and immune signatures.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in immune cell properties from PBMCs after overnight fast and after 2 cycles of fasting mimicking diet compared to baseline.	PBMCs retrieved from whole blood samples will be analysed with a 40-plex Aurora flowcytometry panel with markers for T cells and myeloid cells. The flow cytometry will generate frequencies of the different immune cell markers,. A comparison of the frequency data between blood samples will determine change in immune cell properties. This analysis will be used to confirm and complement gene expression signature findings on a protein level.	6 months
Change in plasma concentration of IGF1, glucose and ketone bodies (Beta-hydroxybutyric acid) after overnight fast and after completion of 2 cycles of fasting mimicking diet compared to baseline.	Measured in blood plasma taken at 3 time points.	4 weeks
Percentage of participants reporting adverse events as assessed by CTCAE v5.0 during fasting mimicking diet	Descriptive analysis of adverse events by type and grade according to NCI CTCAE v5.0 experienced by participants during fasting mimicking diet assessed after second cycle on day 22.	8 weeks

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Investigators: Principal Investigator: Judith R Kroep, Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2021
• Primary Completion (Actual): April 1, 2022
• Study Completion (Actual): April 28, 2022

Study Registration Dates

• First Submitted: March 30, 2021
• First Submitted That Met QC Criteria: April 2, 2021
• First Posted (Actual): April 6, 2021

Study Record Updates

• Last Update Posted (Actual): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Fasting; Immunomodulation; Caloric restriction; Tumor-Infiltrating Lymphocytes; Fasting Mimicking Diet
• Other Study ID Numbers: NL76033.058.21; P21.017 (Other Identifier: LUMC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No