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

NCT ID: NCT04247464

Last Updated: 2023-10-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-23

Study Completion Date

2023-02-01

Brief Summary

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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

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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

Conditions

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Fasting

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard diet

The participants will follow an standard diet during the chemotherapy treatment

Group Type NO_INTERVENTION

No interventions assigned to this group

Fasting

The participants will follow a short-term fasting period for 44-48 hours, starting 24 hours before chemotherapy treatment

Group Type EXPERIMENTAL

Fasting

Intervention Type PROCEDURE

Food intake restriction

Interventions

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Fasting

Food intake restriction

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital Infanta Sofia

OTHER

Sponsor Role collaborator

Hospital Universitario La Paz

OTHER

Sponsor Role collaborator

IMDEA Food

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Enrique Casado, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Infanta Sofia

Francisco Zambrana, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario Infanta Sofia

Pablo J Fernandez-Marcos, PhD

Role: PRINCIPAL_INVESTIGATOR

IMDEA Food

Jaime Feliu, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario La Paz

Nuria Rodríguez-Salas, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario La Paz

Ismael Ghanem- Cañete, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario La Paz

Locations

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IMDEA Food

Madrid, , Spain

Site Status

Countries

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Spain

References

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Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res Rev. 2017 Oct;39:46-58. doi: 10.1016/j.arr.2016.10.005. Epub 2016 Oct 31.

Reference Type BACKGROUND
PMID: 27810402 (View on PubMed)

Duan W, Guo Z, Jiang H, Ware M, Mattson MP. Reversal of behavioral and metabolic abnormalities, and insulin resistance syndrome, by dietary restriction in mice deficient in brain-derived neurotrophic factor. Endocrinology. 2003 Jun;144(6):2446-53. doi: 10.1210/en.2002-0113.

Reference Type BACKGROUND
PMID: 12746306 (View on PubMed)

Arumugam TV, Phillips TM, Cheng A, Morrell CH, Mattson MP, Wan R. Age and energy intake interact to modify cell stress pathways and stroke outcome. Ann Neurol. 2010 Jan;67(1):41-52. doi: 10.1002/ana.21798.

Reference Type BACKGROUND
PMID: 20186857 (View on PubMed)

Arnason TG, Bowen MW, Mansell KD. Effects of intermittent fasting on health markers in those with type 2 diabetes: A pilot study. World J Diabetes. 2017 Apr 15;8(4):154-164. doi: 10.4239/wjd.v8.i4.154.

Reference Type BACKGROUND
PMID: 28465792 (View on PubMed)

Safdie FM, Dorff T, Quinn D, Fontana L, Wei M, Lee C, Cohen P, Longo VD. Fasting and cancer treatment in humans: A case series report. Aging (Albany NY). 2009 Dec 31;1(12):988-1007. doi: 10.18632/aging.100114.

Reference Type BACKGROUND
PMID: 20157582 (View on PubMed)

Raffaghello L, Lee C, Safdie FM, Wei M, Madia F, Bianchi G, Longo VD. Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proc Natl Acad Sci U S A. 2008 Jun 17;105(24):8215-20. doi: 10.1073/pnas.0708100105. Epub 2008 Mar 31.

Reference Type BACKGROUND
PMID: 18378900 (View on PubMed)

Tinkum KL, Stemler KM, White LS, Loza AJ, Jeter-Jones S, Michalski BM, Kuzmicki C, Pless R, Stappenbeck TS, Piwnica-Worms D, Piwnica-Worms H. Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival. Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):E7148-54. doi: 10.1073/pnas.1509249112. Epub 2015 Dec 7.

Reference Type BACKGROUND
PMID: 26644583 (View on PubMed)

Di Biase S, Lee C, Brandhorst S, Manes B, Buono R, Cheng CW, Cacciottolo M, Martin-Montalvo A, de Cabo R, Wei M, Morgan TE, Longo VD. Fasting-Mimicking Diet Reduces HO-1 to Promote T Cell-Mediated Tumor Cytotoxicity. Cancer Cell. 2016 Jul 11;30(1):136-146. doi: 10.1016/j.ccell.2016.06.005.

Reference Type BACKGROUND
PMID: 27411588 (View on PubMed)

Pietrocola F, Pol J, Vacchelli E, Rao S, Enot DP, Baracco EE, Levesque S, Castoldi F, Jacquelot N, Yamazaki T, Senovilla L, Marino G, Aranda F, Durand S, Sica V, Chery A, Lachkar S, Sigl V, Bloy N, Buque A, Falzoni S, Ryffel B, Apetoh L, Di Virgilio F, Madeo F, Maiuri MC, Zitvogel L, Levine B, Penninger JM, Kroemer G. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance. Cancer Cell. 2016 Jul 11;30(1):147-160. doi: 10.1016/j.ccell.2016.05.016.

Reference Type BACKGROUND
PMID: 27411589 (View on PubMed)

Lopez-Guadamillas E, Fernandez-Marcos PJ, Pantoja C, Munoz-Martin M, Martinez D, Gomez-Lopez G, Campos-Olivas R, Valverde AM, Serrano M. p21Cip1 plays a critical role in the physiological adaptation to fasting through activation of PPARalpha. Sci Rep. 2016 Oct 10;6:34542. doi: 10.1038/srep34542.

Reference Type BACKGROUND
PMID: 27721423 (View on PubMed)

Caffa I, D'Agostino V, Damonte P, Soncini D, Cea M, Monacelli F, Odetti P, Ballestrero A, Provenzani A, Longo VD, Nencioni A. Fasting potentiates the anticancer activity of tyrosine kinase inhibitors by strengthening MAPK signaling inhibition. Oncotarget. 2015 May 20;6(14):11820-32. doi: 10.18632/oncotarget.3689.

Reference Type BACKGROUND
PMID: 25909220 (View on PubMed)

Bouwens M, Afman LA, Muller M. Fasting induces changes in peripheral blood mononuclear cell gene expression profiles related to increases in fatty acid beta-oxidation: functional role of peroxisome proliferator activated receptor alpha in human peripheral blood mononuclear cells. Am J Clin Nutr. 2007 Nov;86(5):1515-23. doi: 10.1093/ajcn/86.5.1515.

Reference Type BACKGROUND
PMID: 17991667 (View on PubMed)

Other Identifiers

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HULP PI-3536

Identifier Type: -

Identifier Source: org_study_id

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