Dietary Habits, Metabolome, Immune Profile and Microbiota in Patients With Bone Sarcoma

Osteosarcoma Clinical Trial

— Metabol-Sarc  

Official title:

Evaluation of Dietary Habits, Metabolome, Immune Profile and Microbiota in Patients With Bone Sarcoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04735289
• Other study ID #: 919/2020/Oss/IOR
• Status: Recruiting
• Start date: March 10, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: August 2023
• Source: Istituto Ortopedico Rizzoli
• Contact: Alessandra Longhi, MD
• Phone: +39 (051) 6366-991
• Email: alessandra.longhi[@]ior.it
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Osteosarcoma and Ewing sarcoma treatment has not changed in the last 30 years.

For other types of cancer the epidemiologic and prognostic correlations between dietary behavior, lifestyle and metabolic alterations (i.e.obesity, insulin-resistance) are well known (breast cancer, prostate cancer, colon cancer). However, no epidemiological or prognostic data are available about the metabolic profile and lifestyle behaviors in patients with osteosarcoma and Ewing'sarcoma and only few preclinical studies are available. An in vitro study showed a higher glucose and glutamine consumption from metastatic osteosarcoma cells compared to primary tumor osteosarcoma cells. The effect of the intestinal microbiota into the metabolism of nutrients, drugs, inflammation, epigenetic and immune response was found not only correlated to gastrointestinal tumors but also to other tumors outside gastrointestinal system as well The aim of this study is to investigate if there are differential dietary habits, metabolome, microbiota or immune profile in patients with bone sarcoma compared to a control population in a 1:2 multicenter study.

Description:

MATERIALS & METHODS A population of 270 patients of >12 yrs old (pediatric and adults) with new diagnosis of osteosarcoma and Ewing sarcoma will be included. A detailed dietary intake assessment will be done with EPIC-COS food frequency questionnaire (FFQ) and anthropometric measures (Weight, Height, body fat/lean mass composition) will be taken at diagnosis before treatment and compared to 540 controls matched by age, sex, and italian geographic area.

In addition, inside this main study a pilot study of 55 patients and 110 controls of same age, sex, geographic area will be performed for analysis of metabolome, microbiota, and immune profile.

At diagnosis, before any treatment , a blood sample will be obtained for metabolomics analyses (untargeted approach with over 100.000 of metabolites, (Mass Spectrometry method) and to evaluate lymphocyte subpopulations (CD3, CD4, CD8, NK) in blood. Microbiota will be analyzed in donated stool samples using the S16 method. All data will be analyzed for inter-correlations among the different parameters and to investigate putative associations with EPIC-COS Food Frequency questionnaires and anthropometric data .

STATISTICAL ANALYSIS Conditional logistic regression analyses will be used to calculate odds ratio (OR) and 95% confidence interval (CI) to investigate associations between dietary habits and bone sarcoma risk in the case control study. An odds ratio of 1.6 with a potency of 85% was considered in the sample size calculations, leading to a target sample size of 270 cases with 540 matched healthy controls.

For the pilot cohort samples of 55 cases and 110 controls will be analyzed for metabolome, microbiota and immune profile. According to the results of this pilot study further cases among the population of FFQ study will undertake further analysis of metabolome and/or microbiota and/or lymphocyte subpopulation to confirm the results of pilot study.

OBJECTIVES OF THE STUDY

1. Compare the diet habits and anthropometric measures in bone sarcoma patients at diagnosis with matched controls

2. Pilot study: in the first 55 pts and their matched 110 healthy voluntary controls will be explored:

1. the occurrence of altered or more recurrent metabolites in patients' blood compared to controls

2. different microbiota diversity and composition between patients and case controls

3. different lymphocytes subpopulations composition.

Bioinformatics analysis will be performed to investigate these objectives

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 810
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Osteosarcoma and Ewing sarcoma first diagnosis

• No previous chemotherapy treatment

• = 12 years old

• Able to understand the questionnaire

• No malignant tumor diagnosis for the last 5 years

• Control case should have a range of +/- 2 years old for patients >= 21 years old. For patients between 12 and 21 years old the difference should be +/- 1 years.

Exclusion Criteria:

• Other tumor type

• Not able to understand the questionnaire

• Patient diagnosed for malignant tumor during the last 5 years

Related Conditions & MeSH terms

• Ewing Sarcoma
• Osteosarcoma
• Sarcoma
• Sarcoma, Ewing

Intervention

Other:
• EPIC-COS Food Frequency Questionnaire diet Evaluation
Anthropometric measurements (Body mass Index, Lean and fat body composition evaluation) and diet habits evaluation with EPIC-COS-FFQ
• Metabolome, Microbiota, Lymphocytes subpopulations
At diagnosis before any treatment for bone sarcoma will be obtained : a blood sample for metabolomics analyses a stool sample for microbiota analysis Lymphocyte subpopulations (CD3, CD4, CD8, NK) will be analyzed in blood samples

Locations

Country	Name	City	State
Italy	Rizzoli Orthopedic Institute - Bologna	Bologna
Italy	IRCCS Candiolo Cancer Institute	Candiolo	Torino
Italy	Ospedale pediatrico Meyer - U.O. Pediatric Oncoematology	Firenze
Italy	IRCCS Istituto Nazionale Tumori - U.O. Pediatric Oncology	Milano
Italy	Azienda Ospedaliero Universitaria Pisana - U.O. Pediatric Oncoematology	Pisa
Italy	Regina Elena Cancer Center	Roma
Italy	Ospedale Regina Margherita - U.O. Pediatric Oncoematology	Torino

Sponsors (2)

Lead Sponsor	Collaborator
Istituto Ortopedico Rizzoli	International Agency for Research on Cancer

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Albini A, Briga D, Conti M, Bruno A, Farioli D, Canali S, Sogno I, D'Ambrosio G, Consonni P, Noonan DM. SANIST: a rapid mass spectrometric SACI/ESI data acquisition and elaboration platform for verifying potential candidate biomarkers. Rapid Commun Mass S — View Citation

Fritsche-Guenther R, Gloaguen Y, Kirchner M, Mertins P, Tunn PU, Kirwan JA. Progression-Dependent Altered Metabolism in Osteosarcoma Resulting in Different Nutrient Source Dependencies. Cancers (Basel). 2020 May 27;12(6):1371. doi: 10.3390/cancers12061371 — View Citation

Fulbright LE, Ellermann M, Arthur JC. The microbiome and the hallmarks of cancer. PLoS Pathog. 2017 Sep 21;13(9):e1006480. doi: 10.1371/journal.ppat.1006480. eCollection 2017 Sep. No abstract available. — View Citation

Garrett WS. Cancer and the microbiota. Science. 2015 Apr 3;348(6230):80-6. doi: 10.1126/science.aaa4972. — View Citation

Lynch SV, Pedersen O. The Human Intestinal Microbiome in Health and Disease. N Engl J Med. 2016 Dec 15;375(24):2369-2379. doi: 10.1056/NEJMra1600266. No abstract available. — View Citation

Soldati L, Di Renzo L, Jirillo E, Ascierto PA, Marincola FM, De Lorenzo A. The influence of diet on anti-cancer immune responsiveness. J Transl Med. 2018 Mar 20;16(1):75. doi: 10.1186/s12967-018-1448-0. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diet habits in patients versus case controls measured by EPIC COS FFQ	Diet habits from osteosarcoma and Ewing sarcoma patients will be compared with diet habits from a control population. The diet habits data will be evaluated EPIC COS FFQ( European Prospective Investigation Into Cancer and Nutrition Case Only Study Food Frequency Questionnaire) which report: the food consumptions in the last 12 months; - Main food groups (water and other drinks, grain products, fruits and vegetables, legumes, meat and fish products, dairy products, sweets and savory snacks); FFQ-EPIC COS can be accessed on PubMed (PMID: 12484126 and PMID: 12484120).	At diagnosis, up to 4 years
Primary	Diet Quality Index -	Diet quality index from osteosarcoma and Ewing sarcoma patients will be compared with diet habits from a control population. Data will be accessed with EPIC COS FFQ( European Prospective Investigation Into Cancer and Nutrition Case Only Study Food Frequency Questionnaire ); - Diet quality index will be calculated to compare adherence to dietery guidelines and it will be expressed in percentage	At diagnosis, up to 4 years
Primary	Number of patients overweight and obese measured by Body mass index (BMI compared to controls)	Body Mass Index (BMI) measure will be achieved in patients and controls by impedance Tanita scale model BC545 based on height (in centimeters) and weight (in Kilograms) expressed in subjects >18yrs as 1) underweight if <18.5, 2) normal weight 18.5 to 25,3)overweight 25-30 and 4) obese >30.; BMI measure will be achieved by impedance Tanita scale model BC545 in study patients at diagnosis and compared with a control subjects.	At diagnosis, up to 4 years
Primary	Body composition	Lean mass and fat mass will be calculated via impedance Tanita scale model BC545 as a percentage of total weight .Lean body mass is the difference between total body weight and body fat weight, expressed as percentage (%)	At diagnosis, up to 4 years
Secondary	Concentration of blood metabolites - Metabolome	Concentration of untargeted blood metabolites obtained via mass spectometry SANIST technique from blood of 55 patients and from 110 control subject blood. Metabolome will be analyzed in order to determine if there is an occurrence of altered or more recurrent metabolites in patients' blood compared to controls.	At diagnosis, up to 4 years
Secondary	Microbiota	Microbiota will be analyzed with S16 method. Microbiota diversity and composition between patients and controls will be analyzed and expressed as alpha and beta diversity	At diagnosis, up to 4 years
Secondary	Concentrations of lymphocytes subpopulation	Concentrations of (CD3,CD4.CD8,NK) lymphocytes subpopulation will be detected onceat diagnosis before any treatment for sarcoma and they will beexpressed as total number.; The lymphocytes subpopulation will be measured once at diagnosis in study patients and matched controls.	At diagnosis, up to 4 years
Secondary	Lipid profile and Glucidic profile	Fatty acids triglycerids(mg/dL), total cholesterol (mg/dL), HDLcholesterol (mg/dL) and LDL cholesterol (mg/dL), glucose (mg/dL) will be measured once in blood at diagnosis in study patients and control subjects	At diagnosis, up to 4 years