Nutritional Intervention-induced Weight Loss During the Oncological Treatment of Obesity-related Breast Cancer

NCT06046755 | Unknown

• 1 other identifier: 2021/293
• Study Type: interventional
• Target: 220
• Locations: 0 countries
• Sites: N/A

Brief Summary

Obesity could become the first evitable cause of breast cancer in the near future. Due to the relatively slow rate of development in this field, greater efforts must be applied in this area. The HYPOTHESIS of this work is that "a therapy to lose weight in breast cancer women with obesity during the oncological treatment could contribute to slowing carcinogenesis, and to improve the response to the chemotherapy, survival and prevent future recurrences by erasing deleterious epigenetic marks". A group of breast cancer women with obesity (n=90) will be treated to lose weight during the oncologic treatment with a low calorie-ketogenic diet or a group educational intervention program of healthy lifestyle. The reversibility of the obesity-related breast cancer epigenetic signatures (EPIC array and pyrosequencing) and other molecular features (QRTPCR, ELISA assays) in blood leukocytes and plasma and the progression of disease will be compared with an obesity (n=30) and normalweight (n=30) group under conventional anticancer therapy. A matched-group of tumor-free women (n=60) with obesity will be also treated to lose weight with the same nutritional interventions and compared with tumor-free women with normal weight (n=30) in order to evaluate the potential preventive function of weight loss therapies on cancer-related odds. The outcomes of this project will directly benefit overweight and obese patients from healthcare systems, and also to have an economic value supporting pharmaceutical and food industry companies in the design of innovative treatments, useful biomarkers and preventive tools.

Conditions

Breast Cancer; Obesity; Weight Change, Body; Epigenetic Disorder

Keywords

Breast cancer; Obesity; Body composition; Adipose tissue; Weight loss; Ketogenic diet; Group Educational Intervention; DNA methylation; Hormonal adjuvance

Outcome Measures

Primary Outcomes (10)

• Weight loss

  Changes in body weight induced by the nutritional intervention therapies

  4 months

• Fat mass in kg

  Changes in fat mass induced by the nutritional intervention therapies

  4 months

• Fat free mass in kg

  Changes in fat free mass induced by the nutritional intervention therapies

  4 months

• Visceral fat mass in kg

  Changes in visceral fat mass induced by the nutritional intervention therapies

  4 months

• DNA methylation levels

  Changes in the pattern of circulating DNA methylation

  4 months

• Score of quality of life questionnaire

  changes in the score of Quality of life associated to the interventions

  4 months

• Score of Sleep Quality questionnaire

  Changes in the score of Sleep Quality associated to the interventions

  4 months

• Score of Female Sexual Function Index questionnaire

  Changes in the score of Female Sexual Function Index associated to the interventions

  4 months

• Concentration of inflammatory biomarkers

  Changes associated to the interventions in plasmatic levels of cytokines quantified using a commercial multiplex enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturer's instructions. The following cytokines were analyzed: April, B cell activator factor (BAFF), cluster of differentiation (CD)163, CD30, Chitanase, glycoprotein (Gp)130, interferon (IFN)-α2, IFN-β, IFN-γ, interleukin (IL)-2, IL-6R, IL-11, IL-12(p40), IL-12(p70), IL-22, IL-26, IL-28A, IL-29, IL-35, matrix metalloproteinase (MMP)1, MMP3, Osteocalcin, Pentraxin-3, tumor necrosis factor receptor (TNF)-R1, TNF-R2, Thymic stromal lymphopoietin (TSLP) and Tweak.

  4 months

• Concentration of Oxidative stress biomarkers

  Among the oxidative stress biomarkers, the levels of malondialdehyde (MDA) and total antioxidative power (AOP) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) will be evaluated in serum. MDA and AOP will be quantified using colorimetric assay kits . An enzyme immunoassay kit will be used for the quantification of 8-OHdG in the serum.

  4 months

Secondary Outcomes (2)

• Diagnostic of cardiotoxicity

  12 months

• Response to Oncological treatment

  12 months

Study Arms (5)

Energy restriction-ketogenic intervention (VLCKD)-breast cancer arm

EXPERIMENTAL

Breast cancer patients with obesity will follow an energy-restricted-ketogenic dietary five steps program, which includes lifestyle and behavioral modification support. The first three steps consist of a VLCKD (600 -800 kcal/day), low in carbohydrates (\< 50 g daily from vegetables) and lipids (only 10 g of olive oil per day). Throughout these ketogenic phases, supplements of vitamins and minerals supplements, such as K, Na, Mg, Ca, and omega-3 fatty acids will be administered. These three steps will be maintained until the patient lost the target amount of weight, ideally 80%. In steps 4 and 5, the patient started a low-calorie diet (800 -1500 kcal/day) and followed by a maintenance diet that will consist of an eating plan balanced in carbohydrates, protein, and fat (1500 and 2000 kcal/day).

Other: Very low calorie ketogenic diet (VLCKD)

Group educational intervention program (IGOBE)-breast cancer arm

EXPERIMENTAL

Breast cancer patients with obesity will follow structured program of change of habits that will consist of a balanced hypocaloric diet, following the criteria of both the recommendations from Spanish Society of Study of Obesity (SEEDO) 2007, the American Dietetic Guidelines 2010, the Consensus SEEDO 2012 and the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society Guideline for the Management of Overweight and Obesity in Adults 2014. Coinciding all in pointing out that the hypocaloric diet should represent a deficit of about 500 to 1000 kcal / day with respect to the habitual intake of the patient in question. The intervention group will be included in a structured program of habits change and exercise. In the intensive phase of the intervention patients will assist to 6 additional weekly visits, with 15 patients per group and a duration of 60 minutes each.

Behavioral: Group educational intervention program (IGOBE)

Energy restriction-ketogenic intervention (VLCKD)-tumor free arm

EXPERIMENTAL

Tumor-free patients with obesity will follow an energy-restricted-ketogenic dietary five steps program, which includes lifestyle and behavioral modification support. The first three steps consist of a VLCKD (600 -800 kcal/day), low in carbohydrates (\< 50 g daily from vegetables) and lipids (only 10 g of olive oil per day). Throughout these ketogenic phases, supplements of vitamins and minerals supplements, such as K, Na, Mg, Ca, and omega-3 fatty acids will be administered. These three steps will be maintained until the patient lost the target amount of weight, ideally 80%. In steps 4 and 5, the patient started a low-calorie diet (800 -1500 kcal/day) and followed by a maintenance diet that will consist of an eating plan balanced in carbohydrates, protein, and fat (1500 and 2000 kcal/day).

Other: Very low calorie ketogenic diet (VLCKD)

Group educational intervention program (IGOBE)-tumor free arm

EXPERIMENTAL

Tumor-free patients with obesity will follow structured program of change of habits that will consist of a balanced hypocaloric diet, following the criteria of both the recommendations from Spanish Society of Study of Obesity (SEEDO) 2007, the American Dietetic Guidelines 2010, the Consensus SEEDO 2012 and the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society Guideline for the Management of Overweight and Obesity in Adults 2014. Coinciding all in pointing out that the hypocaloric diet should represent a deficit of about 500 to 1000 kcal / day with respect to the habitual intake of the patient in question. The intervention group will be included in a structured program of habits change and exercise. In the intensive phase of the intervention patients will assist to 6 additional weekly visits, with 15 patients per group and a duration of 60 minutes each.

Behavioral: Group educational intervention program (IGOBE)

Non intervention arm-breast cancer arm

NO INTERVENTION

This arm will include patients with obesity and normal weight women with breast cancer that will follow the normal clinical practice in their oncological therapy without intervention to lose weight in the group of patients with excess body weight.

Interventions

Very low calorie ketogenic diet (VLCKD) OTHER

Weight loss therapies in patients with excess body weight based on a ketogenic diet

Energy restriction-ketogenic intervention (VLCKD)-breast cancer arm; Energy restriction-ketogenic intervention (VLCKD)-tumor free arm

Group educational intervention program (IGOBE) BEHAVIORAL

Balanced hypocaloric diet plus structured groupal program of habits change and exercise

Group educational intervention program (IGOBE)-breast cancer arm; Group educational intervention program (IGOBE)-tumor free arm

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal women
• Primary, histologically confirmed, incident breast cancer diagnostic

You may not qualify if:

• Thyroid disorder,
• Diabetes mellitus,
• Cardiovascular disease,
• cerebrovascular disease
• Obesity induced by other endocrine disorders or drugs,
• Participation in any active weight loss program in the previous 3 months.
• Known or suspected narcotic or alcohol abuse,
• Severe depression or any other psychiatric disease,
• Severe liver failure
• Uncontrolled hypertension,
• Orthostatic hypotension,
• hydroelectrolytic or electrocardiographic alterations
• Prescription of drugs that may alter the lipid or glucose profile.

Sponsors & Collaborators

• Hospital Clinico Universitario de Santiago: lead
• Hospital Arquitecto Marcide: collaborator

Related Publications (8)

• Cabia B, Andrade S, Carreira MC, Casanueva FF, Crujeiras AB. A role for novel adipose tissue-secreted factors in obesity-related carcinogenesis. Obes Rev. 2016 Apr;17(4):361-76. doi: 10.1111/obr.12377. Epub 2016 Feb 24.

  PMID: 26914773 BACKGROUND

• Crujeiras AB, Cabia B, Carreira MC, Amil M, Cueva J, Andrade S, Seoane LM, Pardo M, Sueiro A, Baltar J, Morais T, Monteiro MP, Lopez-Lopez R, Casanueva FF. Secreted factors derived from obese visceral adipose tissue regulate the expression of breast malignant transformation genes. Int J Obes (Lond). 2016 Mar;40(3):514-23. doi: 10.1038/ijo.2015.208. Epub 2015 Oct 26.

  PMID: 26443342 BACKGROUND

• Crujeiras AB, Cueva J, Vieito M, Curiel T, Lopez-Lopez R, Pollan M, Casanueva FF. Association of breast cancer and obesity in a homogeneous population from Spain. J Endocrinol Invest. 2012 Jul;35(7):681-5. doi: 10.3275/8370. Epub 2012 Apr 18.

  PMID: 22522745 BACKGROUND

• Crujeiras AB, Diaz-Lagares A, Carreira MC, Amil M, Casanueva FF. Oxidative stress associated to dysfunctional adipose tissue: a potential link between obesity, type 2 diabetes mellitus and breast cancer. Free Radic Res. 2013 Apr;47(4):243-56. doi: 10.3109/10715762.2013.772604. Epub 2013 Feb 26.

  PMID: 23409968 BACKGROUND

• Crujeiras AB, Diaz-Lagares A, Sandoval J, Milagro FI, Navas-Carretero S, Carreira MC, Gomez A, Hervas D, Monteiro MP, Casanueva FF, Esteller M, Martinez JA. DNA methylation map in circulating leukocytes mirrors subcutaneous adipose tissue methylation pattern: a genome-wide analysis from non-obese and obese patients. Sci Rep. 2017 Feb 17;7:41903. doi: 10.1038/srep41903.

  PMID: 28211912 BACKGROUND

• Crujeiras AB, Diaz-Lagares A, Stefansson OA, Macias-Gonzalez M, Sandoval J, Cueva J, Lopez-Lopez R, Moran S, Jonasson JG, Tryggvadottir L, Olafsdottir E, Tinahones FJ, Carreira MC, Casanueva FF, Esteller M. Obesity and menopause modify the epigenomic profile of breast cancer. Endocr Relat Cancer. 2017 Jul;24(7):351-363. doi: 10.1530/ERC-16-0565. Epub 2017 Apr 25.

  PMID: 28442560 BACKGROUND

• Gomez-Arbelaez D, Bellido D, Castro AI, Ordonez-Mayan L, Carreira J, Galban C, Martinez-Olmos MA, Crujeiras AB, Sajoux I, Casanueva FF. Body Composition Changes After Very-Low-Calorie Ketogenic Diet in Obesity Evaluated by 3 Standardized Methods. J Clin Endocrinol Metab. 2017 Feb 1;102(2):488-498. doi: 10.1210/jc.2016-2385.

  PMID: 27754807 BACKGROUND

• Izquierdo AG, Carreira MC, Amil M, Mosteiro CS, Garcia-Caballero T, Fernandez-Quintela A, Portillo MP, Casanueva FF, Crujeiras AB. An energy restriction-based weight loss intervention is able to reverse the effects of obesity on the expression of liver tumor-promoting genes. FASEB J. 2020 Feb;34(2):2312-2325. doi: 10.1096/fj.201901147RR. Epub 2019 Dec 16.

  PMID: 31908001 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Obesity; Body Weight Changes; Weight Loss

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Ana B Crujeiras, Dr

  Hospital Clinico Universitario de Santiago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ana B Crujeiras, Dr

CONTACT

+34 981955710; ana.belen.crujeiras.martinez@sergas.es

Teresa Cabaleiro

CONTACT

+34 981 951 628; ma.teresa.cabaleiro.ocampo@sergas.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Researcher

Model Details: Postmenopausal women (n=130) diagnosed with primary, histologically confirmed, incident postmenopausal breast cancer and with 50-70 years at diagnosis will be recruited. A group of 60 breast cancer patients with obesity (BMI≥30) will be invited to follow a weight loss treatment based on a 4 months-energy restriction-ketogenic intervention arm or a behavioural group intervention. Those groups will be compared with a non-intervention control arm of with 30 breast cancer with obesity and 30 normal weight women. On the other hand, a group of 90 tumor-free postmenopausal women (50-17 years) will be recruited in the Endocrinology and Nutrition Service of reference hospitals where 30 women will have a normal weight and the other 60 will be women with obesity. These last women will be subjected to a 4 months-energy restriction-ketogenic intervention arm or a behavioural group intervention and compared with a group of tumor-free normal weight subjects.

Study Record Dates

• First Submitted: July 21, 2023
• First Posted: September 21, 2023
• Study Start: October 15, 2023
• Primary Completion: October 3, 2024
• Study Completion: December 21, 2025
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share