Clinical trial NCT04247464: Short-term Fasting as an Enhancer of Chemotherapy: Pilot Clinical Study on Colorectal Carcinoma Patients
Official title: Evaluation of Short-term Fasting Effects on Chemotherapy Toxicity and Efficacy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Fasting
Keywords: Short-term Fasting
Colorectal Cancer
Chemotherapy
Toxicity
Immune response
Lead sponsor: IMDEA Food
Sponsor class: OTHER
Collaborators: name: Hospital Infanta Sofia
name: Hospital Universitario La Paz
First posted: 2020-01-30
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Changes in the Common Terminology Criteria for Adverse Events CTCAE 5.0 toxicity table score.
timeFrame: Baseline and after three weeks
measure: Changes in the immune response
timeFrame: Baseline and after three weeks
measure: Changes in the correlation between chemotherapy response and p21 and/or other fasting genes expression in peripheral blood mononuclear cells (PBMCs)
timeFrame: Baseline and after three weeks
Secondary outcomes:
measure: Subjective evaluation of tolerance to fasting
timeFrame: 48 hours of fasting, including 24 hours prior and 24 hours after chemotherapy administration.
measure: Changes in glycemia in response to fasting
timeFrame: Baseline and after three weeks
measure: Changes in Free Fatty Acids levels in response to fasting
timeFrame: Baseline and after three weeks
measure: Changes in Insulin levels in response to fasting
timeFrame: Baseline and after three weeks
measure: Changes ketone bodies in response to fasting
timeFrame: Baseline and after three weeks
measure: Changes in gene expression in PBMCs after fasting
timeFrame: Baseline and after three weeks
measure: Antitumoral response associated to fasting after chemotherapy treatment
timeFrame: Baseline and after three weeks
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: IMDEA Food
Study officials:
affiliation: Hospital Universitario Infanta Sofia
name: Enrique Casado, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario Infanta Sofia
name: Francisco Zambrana, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IMDEA Food
name: Pablo J Fernandez-Marcos, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario La Paz
name: Jaime Feliu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario La Paz
name: Nuria Rodríguez-Salas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario La Paz
name: Ismael Ghanem- Cañete, MD
role: PRINCIPAL_INVESTIGATOR
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