The Oral Microbiome as a Prognostic Tool in Oral Malignant and Premalignant Lesions and in Medication Related Osteonecrosis of the Jaw

January 14, 2020 updated by: Irit Allon, Barzilai Medical Center
Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck, and its incidence has increased in recent years. Extensive surgery with neck dissection and chemo/radio/ targeted therapy is the current treatment for OSCC, and despite great progress in chemotherapy, radiotherapy, and targeted therapy in the last three decades, the prognosis of OSCC is still poor due to aggressive local invasion and metastasis, which lead to recurrence. Postoperative tumor recurrence confers a poor prognosis in OSCC and a poor quality of life. The 5-year survival rate is over 90% in OSCC patients without recurrence and 30% in patients with recurrence, with a median survival of 76.8 months in patients without recurrence and 42.5 months in patients with recurrence . Therefore, it is important to identify biomarkers that may predict the postoperative recurrence of OSCC. Also, some of the OSCC are preceded by precursor lesions. In the oral cavity the most common lesions recognized as potentially malignant are leukoplakia and erythroplakia, but it is also apparent that as many as 50% of OSCC arise from apparently clinically normal mucosa. The prognostic significance of an individual lesion is difficult to determine. At present therefore, the gold standard for the assessment of oral potentially malignant lesions is microscopic evaluation of haematoxylin and eosin stained sections for the presence of architectural and cytological changes, which are generally referred to as oral epithelial dysplasia (OED). The human microbiome is defined as the collective genomes of the microbes (composed of bacteria, bacteriophages, fungi, protozoa and viruses) that live inside and on the human body, and there are approximately 10 microbes and 100 microbial genes for each human cell and gene respectively. With the advent of next generation sequencing technology, the Human Microbiome Project delineated the composition of healthy microbial communities associated to different body sites in healthy individuals, including the oral cavity [Human microbiome consortium]. As opposed to a normal (healthy) microbiome, a disrupted microbiome or dysbiosis represents the lack of equilibrium, and is hypothetically related to disease. Interestingly, the healthy oral microbiome shows relative intraindividual stability over time, suggesting that differences in microbiome profiles may serve as useful tools for the identification of disease states. The working hypothesis is that in OSCC patients, the oral microbiome is altered in comparison to healthy individuals and certain microbial signatures are characteristic of healthy versus disease. In addition, in precursor conditions, i.e., oral epithelial dysplasia (OED), a partial alteration in the composition of the microbiome may predict the progression to malignancy.Also, during treatment, it could be that specific microbial signatures are associated with incomplete eradication, tendency to local recurrence or metastatic potential.Correlations to local recurrence (LR), distant metastases (DM) or disease free survival (DFS) adjusted to clinicopathologic correlations will be sought. In this study, buccal mucosa samples will be collected from patients with OSCC, OED and from healthy individuals , after signing for informed consent, according to Helsinki protocol. Routine pathologic diagnosis will be performed by expert Pathology physicians in our center. Data will be correlated to demographic and clinical data obtained from medical records. This will be carried out in line with institutional ethical guidelines.

Study Overview

Study Type

Observational

Enrollment (Anticipated)

150

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Ashkelon, Israel
        • Recruiting
        • Barzilai Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The study population will be selected from the Oral & Maxillofacial Surgery outpatient Clinique at the Barzilai Medical Center, Ashkelon, Israel

Description

Inclusion Criteria:

  • Patients biopsied with OSCC
  • Patients biopsied with oral premalignant lesions
  • Patients biopsied with osteonecrosis of the jaw
  • healthy age matched patients that visit the oral and maxillofacial clinic for other purposes such as extraction, reactive lesions

Exclusion Criteria:

  • Patients receiving antimicrobial treatment in the previous 3 months
  • Patients receiving radiotherapy
  • Patients receiving chemo/immunotherapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Oral Squamous Cell Carcinoma
Buccal mucosa samples for Extraction of BACTERIAL DNA

Sampling of the buccal mucosa after informed consent and prior to routine treatment. Similar sampling on follow up after 3,6,9,12 months.

Extracted BACTERIAL DNA (and not human DNA) from clinical samples will be sequenced and analyzed for the 16s rRNA (BACTERIAL ribosome).

Oral Epithelial Dysplasia
Buccal mucosa samples for Extraction of BACTERIAL DNA

Sampling of the buccal mucosa after informed consent and prior to routine treatment. Similar sampling on follow up after 3,6,9,12 months.

Extracted BACTERIAL DNA (and not human DNA) from clinical samples will be sequenced and analyzed for the 16s rRNA (BACTERIAL ribosome).

Control: Healthy age matched patients
Buccal mucosa samples for Extraction of BACTERIAL DNA

Sampling of the buccal mucosa after informed consent and prior to routine treatment. Similar sampling on follow up after 3,6,9,12 months.

Extracted BACTERIAL DNA (and not human DNA) from clinical samples will be sequenced and analyzed for the 16s rRNA (BACTERIAL ribosome).

Osteonecrosis of the Jaw
Buccal mucosa samples for Extraction of BACTERIAL DNA

Sampling of the buccal mucosa after informed consent and prior to routine treatment. Similar sampling on follow up after 3,6,9,12 months.

Extracted BACTERIAL DNA (and not human DNA) from clinical samples will be sequenced and analyzed for the 16s rRNA (BACTERIAL ribosome).

Underlying disease, no necrosis of the jaw
Buccal mucosa samples for Extraction of BACTERIAL DNA

Sampling of the buccal mucosa after informed consent and prior to routine treatment. Similar sampling on follow up after 3,6,9,12 months.

Extracted BACTERIAL DNA (and not human DNA) from clinical samples will be sequenced and analyzed for the 16s rRNA (BACTERIAL ribosome).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Microbiome characterization day 1 of the study
Time Frame: Day 1 of each participant
Extracted BACTERIAL DNA sequenced by amplification of the V4 region of 16s rRNA (BACTERIAL ribosome). The samples will be obtained by buccal mucosa swabs from all subjects at the clinic visit (day 1). FLOQ swabs (Copan) will be rubbed on the inner cheek mucosa that looks macroscopically normal. The swab will be immediately placed in a 15ml polypropylene tube containing 1 ml of Molecular grade PBS. Samples will be kept at 4oC until frozen at -80oC. Each sample will be assigned a protocol serial number, de-identified from the subject.
Day 1 of each participant
Microbiome characterization month 3 of the study
Time Frame: Month 3 of each participant
1Extracted BACTERIAL DNA sequenced by amplification of the V4 region of 16s rRNA (BACTERIAL ribosome). The samples will be obtained by buccal mucosa swabs from all subjects at the clinic visit (month 3). FLOQ swabs (Copan) will be rubbed on the inner cheek mucosa that looks macroscopically normal. The swab will be immediately placed in a 15ml polypropylene tube containing 1 ml of Molecular grade PBS. Samples will be kept at 4oC until frozen at -80oC. Each sample will be assigned a protocol serial number, de-identified from the subject.
Month 3 of each participant
Microbiome characterization month 6 of the study
Time Frame: Month 6 of each participant
Extracted BACTERIAL DNA sequenced by amplification of the V4 region of 16s rRNA (BACTERIAL ribosome). The samples will be obtained by buccal mucosa swabs from all subjects at the clinic visit (month 6). FLOQ swabs (Copan) will be rubbed on the inner cheek mucosa that looks macroscopically normal. The swab will be immediately placed in a 15ml polypropylene tube containing 1 ml of Molecular grade PBS. Samples will be kept at 4oC until frozen at -80oC. Each sample will be assigned a protocol serial number, de-identified from the subject.
Month 6 of each participant
Microbiome characterization month 9 of the study
Time Frame: Month 9 of each participant
Extracted BACTERIAL DNA sequenced by amplification of the V4 region of 16s rRNA (BACTERIAL ribosome). The samples will be obtained by buccal mucosa swabs from all subjects at the clinic visit (month 9). FLOQ swabs (Copan) will be rubbed on the inner cheek mucosa that looks macroscopically normal. The swab will be immediately placed in a 15ml polypropylene tube containing 1 ml of Molecular grade PBS. Samples will be kept at 4oC until frozen at -80oC. Each sample will be assigned a protocol serial number, de-identified from the subject.
Month 9 of each participant
Microbiome characterization month 12 of the study
Time Frame: Month 12 of each participant
3. Extracted BACTERIAL DNA sequenced by amplification of the V4 region of 16s rRNA (BACTERIAL ribosome). The samples will be obtained by buccal mucosa swabs from all subjects at the clinic visit (month 12). FLOQ swabs (Copan) will be rubbed on the inner cheek mucosa that looks macroscopically normal. The swab will be immediately placed in a 15ml polypropylene tube containing 1 ml of Molecular grade PBS. Samples will be kept at 4oC until frozen at -80oC. Each sample will be assigned a protocol serial number, de-identified from the subject.
Month 12 of each participant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 14, 2017

Primary Completion (Anticipated)

December 31, 2021

Study Completion (Anticipated)

December 31, 2021

Study Registration Dates

First Submitted

January 16, 2018

First Submitted That Met QC Criteria

January 25, 2018

First Posted (Actual)

February 1, 2018

Study Record Updates

Last Update Posted (Actual)

January 18, 2020

Last Update Submitted That Met QC Criteria

January 14, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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