Use of the xCELLigence System for Quantification of Bacterial Biofilm's Real Time Formation and Antibiotics Selection.

Sponsor

University of Valencia (Other)

Overall Status

Unknown status

CT.gov ID

NCT03863249

Collaborator

Centro Superior de Investigación en Salud Publica (Other), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (Other)

Enrollment

Location

Arms

5.7

Anticipated Duration (Months)

10.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of the study is to develop an in vitro model of growth of oral biofilms, and validate xCELLigence system for the selection of an effective antibiotic treatment for each patient.

Condition or Disease	Intervention/Treatment	Phase
Chronic Periodontitis Periodontal Bone Loss Resistance Bacterial	Procedure: SCALE AND ROOT PLANING Drug: ADJUNTIVE ANTIBIOTICS Diagnostic Test: MICROBIAL SAMPLING	Phase 4

Detailed Description

Periodontitis in a chronic disease caused by bacteria present in the subgingival flora, which induces an inflammatory response of periodontal tissues. It has been suggested that some periodontal pathogens may be inaccessible to mechanical periodontal therapy due to its ability to invade the gingival tissues and evade defense mechanisms of the host. Therefore, it is conceivable that coadjuvant administration of antimicrobials may improve the outcome of mechanical therapy. There are several techniques to monitor periodontal pathogens and determine antibiotic therapy. But the most important disadvantage of conventional laboratory methods is that they are indirect, based on the molecular detection of 3 to 10 bacterial species, without analyzing whether the biofilm as a whole is sensitive or resistant to treatment, being a possible cause of failure and / or recurrence of the disease, in addition to the risk of development of antimicrobial resistance.

The investigators hypothesis is that the specific selection of antimicrobial treatment with the xCELLigence system allows better improvements in clinical parameters than indirect laboratory methods.

Materials and methods:

A randomized double-blind clinical trial will be launched. Samples of subgingival plaque will be taken with paper tips. Subjects included in the study will be randomized to one of 3 treatment groups: scaling and root planing combined with systemically administration of antibiotic suggested by the xCELLigence system; scaling and root planing combined with systemically administration of antibiotic suggested by 'Echevarne' laboratory and scaling and root planing combined with systemically administration of antibiotic suggested by 'Origen' laboratory.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double blinded, randomized clinical trial.Double blinded, randomized clinical trial.

Masking:

Double (Participant, Care Provider)

Masking Description:

Double-blinding: The researchers who performed the measurements and treatment will be different from those who performed the microbial analysis; the examiner will be blinded during the entire duration of the study about the type of analysis subgingival dental plaque has been undergone.

Primary Purpose:

Treatment

Official Title:

Use of the xCELLigence System for Quantification of Bacterial Biofilm's Real Time Formation and Antibiotics Selection: Randomized Clinical Trial.

Actual Study Start Date :

Feb 8, 2019

Anticipated Primary Completion Date :

Aug 1, 2019

Anticipated Study Completion Date :

Aug 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: The exCELLigence system Following the baseline examination each of the 20 randomly selected patients will be informed about the cause of periodontal disease. The 10 deepest interproximal sites in each quadrant will be selected and exposed to microbial sampling. Two sterilized paper points will be inserted into the pocket of each site and will be keep in place for 60 s. The twin paper points will be remove and distributed in two vials and transfer for microbiological processing. The study participants will undergo SCALE AND ROOT PLANING (SRP). SRP will be performed two quadrants at a time under local anaesthesia at approximately weekly intervals. The adjunctive antibiotics selected by 'the exCELLingence' system will be started at the second SRP visit.	Procedure: SCALE AND ROOT PLANING SRP will be performed two quadrants at a time under local anaesthesia at approximately weekly intervals. Each session will be carried out with the following materials: - Ultrasound device (SONICflex 2003 / L) and curettes (Hu-Friedy Manufacturing, Illinois, USA). Drug: ADJUNTIVE ANTIBIOTICS The antimicrobial adjunctive agents selected by 'Echevarne' laboratories analysis will be started at the second SRP visit. The antibiotic will be selected among AMOXICILIN, METRONIDAZOLE, AMOXICILIN + METRONIDAZOLE AND AZITROMYCIN. Diagnostic Test: MICROBIAL SAMPLING Before treatment, the 10 deepest interproximal sites in each quadrant will be selected and exposed to microbial sampling. Two sterilized paper points will be inserted into the pocket of each site and will be keep in place for 60 s. The twin paper points will be remove and distributed in two vials and transfer for microbiological processing. The subgingival microbiota will be harvested from the sampling sites 2 months after the completion of active therapy.
Active Comparator: Origen Following the baseline examination each of the 20 randomly selected patients will be informed about the cause of periodontal disease. The 10 deepest interproximal sites in each quadrant will be selected and exposed to microbial sampling. Two sterilized paper points will be inserted into the pocket of each site and will be keep in place for 60 s. The twin paper points will be remove and distributed in two vials and transfer for microbiological processing. The study participants will undergo SCALE AND ROOT PLANING (SRP). SRP will be performed two quadrants at a time under local anaesthesia at approximately weekly intervals. The adjunctive antibiotics agents selected by 'Origen' laboratories analysis will be started at the second SRP visit.	Procedure: SCALE AND ROOT PLANING SRP will be performed two quadrants at a time under local anaesthesia at approximately weekly intervals. Each session will be carried out with the following materials: - Ultrasound device (SONICflex 2003 / L) and curettes (Hu-Friedy Manufacturing, Illinois, USA). Drug: ADJUNTIVE ANTIBIOTICS The antimicrobial adjunctive agents selected by 'Echevarne' laboratories analysis will be started at the second SRP visit. The antibiotic will be selected among AMOXICILIN, METRONIDAZOLE, AMOXICILIN + METRONIDAZOLE AND AZITROMYCIN. Diagnostic Test: MICROBIAL SAMPLING Before treatment, the 10 deepest interproximal sites in each quadrant will be selected and exposed to microbial sampling. Two sterilized paper points will be inserted into the pocket of each site and will be keep in place for 60 s. The twin paper points will be remove and distributed in two vials and transfer for microbiological processing. The subgingival microbiota will be harvested from the sampling sites 2 months after the completion of active therapy.
Active Comparator: Echevarne Following the baseline examination each of the 20 randomly selected patients will be informed about the cause of periodontal disease. The 10 deepest interproximal sites in each quadrant will be selected and exposed to microbial sampling. Two sterilized paper points will be inserted into the pocket of each site and will be keep in place for 60 s. The twin paper points will be remove and distributed in two vials and transfer for microbiological processing. The study participants will undergo SCALE AND ROOT PLANING (SRP). SRP will be performed two quadrants at a time under local anaesthesia at approximately weekly intervals. The adjunctive antibiotics agents selected by 'Echevarne' laboratories analysis will be started at the second SRP visit.	Procedure: SCALE AND ROOT PLANING SRP will be performed two quadrants at a time under local anaesthesia at approximately weekly intervals. Each session will be carried out with the following materials: - Ultrasound device (SONICflex 2003 / L) and curettes (Hu-Friedy Manufacturing, Illinois, USA). Drug: ADJUNTIVE ANTIBIOTICS The antimicrobial adjunctive agents selected by 'Echevarne' laboratories analysis will be started at the second SRP visit. The antibiotic will be selected among AMOXICILIN, METRONIDAZOLE, AMOXICILIN + METRONIDAZOLE AND AZITROMYCIN. Diagnostic Test: MICROBIAL SAMPLING Before treatment, the 10 deepest interproximal sites in each quadrant will be selected and exposed to microbial sampling. Two sterilized paper points will be inserted into the pocket of each site and will be keep in place for 60 s. The twin paper points will be remove and distributed in two vials and transfer for microbiological processing. The subgingival microbiota will be harvested from the sampling sites 2 months after the completion of active therapy.

Arm

Intervention/Treatment

Active Comparator: The exCELLigence system

Following the baseline examination each of the 20 randomly selected patients will be informed about the cause of periodontal disease. The 10 deepest interproximal sites in each quadrant will be selected and exposed to microbial sampling. Two sterilized paper points will be inserted into the pocket of each site and will be keep in place for 60 s. The twin paper points will be remove and distributed in two vials and transfer for microbiological processing. The study participants will undergo SCALE AND ROOT PLANING (SRP). SRP will be performed two quadrants at a time under local anaesthesia at approximately weekly intervals. The adjunctive antibiotics selected by 'the exCELLingence' system will be started at the second SRP visit.

Procedure: SCALE AND ROOT PLANING

SRP will be performed two quadrants at a time under local anaesthesia at approximately weekly intervals. Each session will be carried out with the following materials: - Ultrasound device (SONICflex 2003 / L) and curettes (Hu-Friedy Manufacturing, Illinois, USA).

Drug: ADJUNTIVE ANTIBIOTICS

The antimicrobial adjunctive agents selected by 'Echevarne' laboratories analysis will be started at the second SRP visit. The antibiotic will be selected among AMOXICILIN, METRONIDAZOLE, AMOXICILIN + METRONIDAZOLE AND AZITROMYCIN.

Diagnostic Test: MICROBIAL SAMPLING

Before treatment, the 10 deepest interproximal sites in each quadrant will be selected and exposed to microbial sampling. Two sterilized paper points will be inserted into the pocket of each site and will be keep in place for 60 s. The twin paper points will be remove and distributed in two vials and transfer for microbiological processing. The subgingival microbiota will be harvested from the sampling sites 2 months after the completion of active therapy.

Active Comparator: Origen

Following the baseline examination each of the 20 randomly selected patients will be informed about the cause of periodontal disease. The 10 deepest interproximal sites in each quadrant will be selected and exposed to microbial sampling. Two sterilized paper points will be inserted into the pocket of each site and will be keep in place for 60 s. The twin paper points will be remove and distributed in two vials and transfer for microbiological processing. The study participants will undergo SCALE AND ROOT PLANING (SRP). SRP will be performed two quadrants at a time under local anaesthesia at approximately weekly intervals. The adjunctive antibiotics agents selected by 'Origen' laboratories analysis will be started at the second SRP visit.

Procedure: SCALE AND ROOT PLANING

Drug: ADJUNTIVE ANTIBIOTICS

Diagnostic Test: MICROBIAL SAMPLING

Active Comparator: Echevarne

Following the baseline examination each of the 20 randomly selected patients will be informed about the cause of periodontal disease. The 10 deepest interproximal sites in each quadrant will be selected and exposed to microbial sampling. Two sterilized paper points will be inserted into the pocket of each site and will be keep in place for 60 s. The twin paper points will be remove and distributed in two vials and transfer for microbiological processing. The study participants will undergo SCALE AND ROOT PLANING (SRP). SRP will be performed two quadrants at a time under local anaesthesia at approximately weekly intervals. The adjunctive antibiotics agents selected by 'Echevarne' laboratories analysis will be started at the second SRP visit.

Procedure: SCALE AND ROOT PLANING

Drug: ADJUNTIVE ANTIBIOTICS

Diagnostic Test: MICROBIAL SAMPLING

Outcome Measures

Primary Outcome Measures

Clinical measure: Clinical attachment loss (CAL) change [1. Baseline, 2. Reevaluation (60 days after Scale and root planing).]
It is defined as the distance in millimeters between CEJ and the end of the periodontal pocket. The calculation of the depth of the pocket + gingival recession or pocket depth - gingival hyperplasia will be carried out.
Clinical measure: Probing pocket depth (PPD) change [1. Baseline, 2. Reevaluation (60 days after Scale and root planing).]
The probing depth will be measured in six areas (disto-buccal, mediate-vestibular, mesio-buccal, disto-palatal, mid-palatal, and mesio-palatal) of each tooth with Williams PQ-OW 208 396 probe. It will be use with a pressure of 20 grams that is equivalent to the pressure of dropping the weight of the probe without exerting additional pressure.
Clinical measure: Bleeding on probing (BOP) change, Gingival Bleeding Index. [1. Baseline, 2. Reevaluation (60 days after Scale and root planing).]
The "Full mouth bleeding score" (FMBS) will be calculated based on scores of 0 (no bleeding) or 1 (bleeding) after probing depths are checked. Four surfaces per tooth are evaluated: mesial, distal, vestibular and lingual.
O'leary plaque index change [1. Baseline, 2. Reevaluation (60 days after Scale and root planing).]
The percentage of gingival surfaces with presence of plaque in the dentogingival junction of the teeth is found. Four surfaces per tooth are evaluated: mesial, distal, vestibular and lingual.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects of 40-70 years.
No smokers or smokers of less than 10 cigarettes a day.
Patients with periodontitis stages III and IV grades A-B.
Presence of 20 natural teeth, including at least three molar teeth.
Presence of at least 4 sites with at least 6 mm probing depth.
Good general health

Exclusion Criteria:

Smokers of more than 10 cigarettes a day.
Patients who have received periodontal treatment in the previous 12 months.
Patients who have used antibiotics in the last 6 months.
Routine use of oral antiseptics and / or during the previous 3 months.
Systemic conditions that required antibiotic premedication.
Women pregnant or nursing.
Medications that could influence the outcome of periodontal therapy.
Any known allergies to the test antimicrobial agents.
Diabetics.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Marta Reglero Santaolaya	Valencia		Spain	46010

Sponsors and Collaborators

University of Valencia
Centro Superior de Investigación en Salud Publica
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana