Short-term Fasting as an Enhancer of Chemotherapy: Pilot Clinical Study on Colorectal Carcinoma Patients (CHEMOFAST)

October 3, 2023 updated by: IMDEA Food

Evaluation of Short-term Fasting Effects on Chemotherapy Toxicity and Efficacy

This study will evaluate the ability of short-term fasting to reduce chemotherapy toxicity and enhance anti-tumour response in patients with colorectal carcinoma subjected to chemotherapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Fasting for 24-48 hours during chemotherapy improves the response of the immune system against tumors and reduces chemotherapy toxicity through yet unknown mechanisms. The investigators have found that fasting induces the activation of p21, a protein that stops cell proliferation and plays important immune roles. The investigators hypothesize that p21 induction with short-term fasting enhances the immune anti-tumour response and reduces chemotherapy toxicity. To test this, half of the colorectal carcinoma (CRC) participants will follow 48 hours of fasting, 24 before and 24 after chemotherapy, under constant and specialized nutritional supervision. While the other half will follow a standard diet. A complete blood immunological profile at each chemotherapy cycle will be generated in collaboration with expert cytometrists, and gene expression, biochemical parameters, tumor evolution and toxicity markers will be measured. The investigators will (1) perform a complete analysis of immune cells to characterize the immune effects of fasting during chemotherapy; (2) analyze the effects of fasting on genes, metabolites and other molecules, to identify the responsible biological mechanisms, focusing on p21; (3) assess the reduction of chemotherapy toxicity in patients of colorectal carcinoma subjected to short-term fasting during chemotherapy.

Our project will further explore a safe, inexpensive, relatively unexplored and powerful nutritional intervention that can improve the quality of life and survival rates of millions of cancer patients: short-term fasting. Also, our project will have an important scientific impact, since previous reports have not yet described a clear mechanism explaining the beneficial effects of short-term fasting with chemotherapy

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Madrid, Spain, 28049
        • IMDEA Food

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants with malignant colorectal neoplasia
  • Good metabolic state (BMI>22)
  • Good nutritional tests
  • Normal Haematological and biochemical parameters
  • Normal renal and hepatic function
  • No loss of weight during the chemotherapy treatment

Exclusion Criteria:

  • BMI<22
  • Pregnancy or lactating women
  • Bad nutritional state
  • 3% weigh loss during the last month or more than 5% in the last three months
  • Diagnosis of type 2 diabetes mellitus or hypertension
  • Diagnosed hepatic, renal or cardiovascular disease
  • Respiratory of psychiatric disease
  • Nausea or vomiting, gastrointestinal disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Standard diet
The participants will follow an standard diet during the chemotherapy treatment
Experimental: Fasting
The participants will follow a short-term fasting period for 44-48 hours, starting 24 hours before chemotherapy treatment
Procedure: Fasting
Food intake restriction

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in the Common Terminology Criteria for Adverse Events CTCAE 5.0 toxicity table score.
Time Frame: Baseline and after three weeks

To evaluate changes in chemotherapy toxicity, the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 toxicity table score will be calculated, taking into account different analysis and questionnaires on toxicity symptoms.

Analysis will include:

  • Hematological analysis (erythrocytes, thrombocytes, white blood cells, Neutrophil/lymphocyte ratio and Platelet/lymphocyte ratio).
  • Biochemical analysis (sodium, potassium, calcium, phosphate, urea, creatinine, total protein, albumin, bilirubin, alkaline phosphatase, lactate dehydrogenase, alanine transaminase, aspartate transaminases, creatine kinase, troponin T, C Reactive Protein (CRP), cortisol and prealbumin)
  • Subjective symptoms obtained from health questionnaires (hunger, nausea, dizzying, weakness, diarrhea, constipation, gastroesophageal reflux disease)
Baseline and after three weeks
Changes in the immune response
Time Frame: Baseline and after three weeks
To evaluate the effect of short-term fasting on the immune response a complete immune phenotyping by flow cytometry will be done: cluster of differentiation 3 (CD3), cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8) (for T cells); cluster of differentiation 19 (CD19) (for B-cells), the high affinity Interleukin-2 receptor alpha subunit (CD45RA), CD62L (for T cell subsets: Memory, Effector); cluster of differentiation 25 (CD25) and cluster of differentiation 127 (CD127) (both for Treg cells); cluster of differentiation 11b C(D11b) (for granulocytes and macrophages); cluster of differentiation 14 (CD14) (for monocytes); cluster of differentiation antigen 16 (CD16), cluster of differentiation 56 (CD56) (NK cells); cluster of differentiation 15 (CD15) (for granulocytes and monocytes) markers will be analyzed
Baseline and after three weeks
Changes in the correlation between chemotherapy response and p21 and/or other fasting genes expression in peripheral blood mononuclear cells (PBMCs)
Time Frame: Baseline and after three weeks
The expression levels of p21 and/or fasting genes in peripheral blood mononuclear cells (PBMCs) will be correlated with toxicity parameters previously described in the primary outcome measure 1
Baseline and after three weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Subjective evaluation of tolerance to fasting
Time Frame: 48 hours of fasting, including 24 hours prior and 24 hours after chemotherapy administration.
To evaluate the tolerance to fasting, participants will fill in a fasting tolerance test based on the symptoms they feel, this will result in a final score of tolerance to fasting.
48 hours of fasting, including 24 hours prior and 24 hours after chemotherapy administration.
Changes in glycemia in response to fasting
Time Frame: Baseline and after three weeks
Glucose levels (milligrams per milliliter) will be measured with a kit from Abbott Laboratories, by enzymatic spectrophotometric assays using an Architect instrument from Abbot Laboratories.
Baseline and after three weeks
Changes in Free Fatty Acids levels in response to fasting
Time Frame: Baseline and after three weeks
Free fatty acids levels (moles per milliliter) will be evaluated with a kit from Abbott Laboratories, by enzymatic spectrophotometric assays using an Architect instrument from Abbott Laboratories.
Baseline and after three weeks
Changes in Insulin levels in response to fasting
Time Frame: Baseline and after three weeks
Insulin levels (International Units per milliliter) will be measured with a kit from Abbott Laboratories, by luminescent immunoassay using the Architect instrument from Abbott Laboratories.
Baseline and after three weeks
Changes ketone bodies in response to fasting
Time Frame: Baseline and after three weeks
Ketone bodies concentration (moles per milliliter) will be measured with a kit from Sigma-Aldrich, by an enzymatic spectrophotometric assay using an microplate reader from Thermo Fisher.
Baseline and after three weeks
Changes in gene expression in PBMCs after fasting
Time Frame: Baseline and after three weeks

To evaluate changes in gene expression in PBMCs the following fasting genes will be analyzed by qRTPCR:

  • p21
  • Pyruvate Dehydrogenase Kinase 4 (PDK4)
  • Carnitine palmitoyltransferase 1 (CPT1)
  • Adipophilin (ADFP)
  • Solute carrier family 25, member 50 (SLC25A50)
Baseline and after three weeks
Antitumoral response associated to fasting after chemotherapy treatment
Time Frame: Baseline and after three weeks
To evaluate the clinical antitumoral response, different tumoral markers such as carcinoembryonic antigen (CEA) and Carbohydrate antigen (Ca 19.9) will be analyzed in serum samples
Baseline and after three weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IMDEA Food

Collaborators

Hospital Universitario La Paz
Hospital Infanta Sofia

Investigators

  • Principal Investigator: Pablo J Fernandez-Marcos, PhD, IMDEA Food
  • Principal Investigator: Enrique Casado, MD, Hospital Universitario Infanta Sofia
  • Principal Investigator: Francisco Zambrana, MD, Hospital Universitario Infanta Sofia
  • Principal Investigator: Jaime Feliu, MD, Hospital Universitario La Paz
  • Principal Investigator: Nuria Rodríguez-Salas, MD, Hospital Universitario La Paz
  • Principal Investigator: Ismael Ghanem- Cañete, MD, Hospital Universitario La Paz

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 23, 2020

Primary Completion (Actual)

February 1, 2023

Study Completion (Actual)

February 1, 2023

Study Registration Dates

First Submitted

January 14, 2020

First Submitted That Met QC Criteria

January 27, 2020

First Posted (Actual)

January 30, 2020

Study Record Updates

Last Update Posted (Actual)

October 5, 2023

Last Update Submitted That Met QC Criteria

October 3, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • HULP PI-3536

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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