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

NCT04247464 | Completed

• 1 other identifier: HULP PI-3536
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Fasting

Keywords

Short-term Fasting; Colorectal Cancer; Chemotherapy; Toxicity; Immune response

Outcome Measures

Primary Outcomes (3)

• Changes in the Common Terminology Criteria for Adverse Events CTCAE 5.0 toxicity table score.

  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

  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)

  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 Outcomes (7)

• Subjective evaluation 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

  Baseline and after three weeks

• Changes in Free Fatty Acids levels in response to fasting

  Baseline and after three weeks

• Changes in Insulin levels in response to fasting

  Baseline and after three weeks

• Changes ketone bodies in response to fasting

  Baseline and after three weeks

Study Arms (2)

Standard diet

NO INTERVENTION

The participants will follow an standard diet during the chemotherapy treatment

Fasting

EXPERIMENTAL

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

Procedure: Fasting

Interventions

Fasting PROCEDURE

Food intake restriction

Fasting

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• BMI\<22
• Pregnancy or lactating women
• Bad nutritional state
• % 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

Sponsors & Collaborators

• IMDEA Food: lead
• Hospital Infanta Sofia: collaborator
• Hospital Universitario La Paz: collaborator

Study Sites (1)

IMDEA Food

Madrid, 28049, Spain

Location

Related Publications (12)

• 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.

  PMID: 27810402 BACKGROUND

• 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.

  PMID: 12746306 BACKGROUND

• 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.

  PMID: 20186857 BACKGROUND

• 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.

  PMID: 28465792 BACKGROUND

• 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.

  PMID: 20157582 BACKGROUND

• 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.

  PMID: 18378900 BACKGROUND

• 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.

  PMID: 26644583 BACKGROUND

• 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.

  PMID: 27411588 BACKGROUND

• 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.

  PMID: 27411589 BACKGROUND

• 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.

  PMID: 27721423 BACKGROUND

• 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.

  PMID: 25909220 BACKGROUND

• 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.

  PMID: 17991667 BACKGROUND

MeSH Terms

Conditions

Fasting; Intermittent Fasting; Colorectal Neoplasms

Interventions

Angptl4 protein, mouse

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Enrique Casado, MD

  Hospital Universitario Infanta Sofia

  PRINCIPAL INVESTIGATOR

• Francisco Zambrana, MD

  Hospital Universitario Infanta Sofia

  PRINCIPAL INVESTIGATOR

• Pablo J Fernandez-Marcos, PhD

  IMDEA Food

  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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2020
• First Posted: January 30, 2020
• Study Start: September 23, 2020
• Primary Completion: February 1, 2023
• Study Completion: February 1, 2023
• Last Updated: October 5, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)