Probiotics for Improving Post-surgical Healing

Efficacy of Probiotics in Improving Post-surgical Healing for Impacted Tooth Extractions

A randomized, double-blind, placebo-controlled clinical trial will be performed to assess the efficacy of a probiotic containing Lactobacillus reuteri in improving post-surgical wound healing after impacted tooth extractions.

The Primary aim is to evaluate the efficacy of L. reuteri in improving post-extractive healing.

The Secondary aim is to evaluate the efficacy of L. reuteri in association with an antibiotic therapy (amoxicillin) in reducing the incidence and severity of antibiotic-associated gastro-intestinal symptoms.

Study Overview

• Status: Recruiting
• Conditions: Probiotics; Wound Heal; Tooth, Impacted; Gastrointestinal Complication
• Intervention / Treatment: Procedure: Impacted tooth extraction

Detailed Description

Probiotics are defined by the World Health Organization as "live microorganisms which, when administered in adequate amounts, confer a health benefit on the host." Human microbiome is a complex system that contributes to maintaining a good health status in humans. Broad-spectrum antibiotic therapies act against pathogen bacteria but also affect the intestinal microbiome, leading to different side effects such as abdominal pain, gastric pain, nausea, vomit and diarrhea.

The use of probiotics has been advocated as a possible means in reducing intensity and incidence of the symptoms related to antibiotic therapies. Some probiotics like Lactobacillus reuteri (L. reuteri) showed good anti-inflammatory properties and also antimicrobic action, assuming a possible role in wound healing processes.

Few studies have been conducted on the use of L. reuteri in dentistry. Twetman et al. (2018) conducted a trial to assess the efficacy of L. reuteri in improving post-surgical healing in the oral cavity after a punch biopsy, showing promising results. The authors concluded that larger trials may be useful to better clarify the role of probiotics in oral wounds healing. The only data regarding the possible role of L. reuteri in post- extractive healing comes from a pilot study (Walivara at al. 2019) that showed a reduction of the perceived swelling and of the number of disturbed-sleep nights in patients who underwent impacted-tooth extraction and assumed L. reuteri. Authors concluded that larger trials with closer follow-up visits are required to fully understand the clinical correlation.

The primary aim of the present research is to evaluate the efficacy of a probiotic containing L. reuteri in improving post-surgical healing following impacted tooth extractions and the secondary aim is to investigate its possible role in preventing or reducing gastro-intestinal side effects related to post-operative antibiotic therapy.A Randomized, double-blind, placebo-controlled clinical trial will be performed to evaluate the efficacy of L. reuteri in improving post-extractive healing.

All patients who need impacted tooth extractions at University Hospital of Pisa (Operative Unit of Odontostomatology and Oral Surgery) will be considered eligible for the study.

The number of patients to include is set to 160, divided in two experimental groups (80 patients per group). Patients who meet inclusion/exclusion criteria will be enrolled in this trial.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Antonio Barone, Professor; Phone Number: 050993327; Email: antonio.barone@unipi.it

Study Locations

• Italy
  • Pisa, Italy, 56126
    • Recruiting
    • U.O. Odontostomatologia e Chirurgia del Cavo Orale
    • Contact: Antonio Barone, Professor; Phone Number: 050993327; Email: antonio.barone@unipi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• need for impacted tooth extractions
• over age 18
• ability to understand and to sign an informed consent form

Exclusion Criteria:

• allergy to penicillin
• contraindications to oral surgery
• treatment with immunosuppressive agents or immunocompromised
• treatment with amino-bisphosphonate and anti-angiogenetic medications
• irradiation to head and neck area
• uncontrolled diabetes
• renal failure
• drug and alcohol addiction
• psychiatric disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; All patients will undergo an impacted tooth extraction; patients allocated to group 1 will receive an antibiotic therapy with amoxicillin for 6 days (2 g/day) and a probiotic for 21 days (2 tablets/day).	Procedure: Impacted tooth extraction; All patients will undergo a surgical tooth extraction
Placebo Comparator: Group 2; All patients will undergo an impacted tooth extraction; patients allocated to group 1 will receive an antibiotic therapy with amoxicillin for 6 days (2 g/day) and a placebo of the probiotic for 21 days (2 tablets/day).	Procedure: Impacted tooth extraction; All patients will undergo a surgical tooth extraction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical wound healing	Clinical assessment of the characteristics of the surgical wound	3 days after the surgery
Surgical wound healing	Clinical assessment of the characteristics of the surgical wound	7 days after the surgery
Surgical wound healing	Clinical assessment of the characteristics of the surgical wound	14 days after the surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of pain	presence of pain assessed by VAS (0-10)	3 days after the surgery
Presence of pain	presence of pain assessed by VAS (0-10)	7 days after the surgery
Presence of pain	presence of pain assessed by VAS (0-10)	14 days after the surgery
Abscess	presence of suppuration	3 days after the surgery
Abscess	presence of suppuration	7 days after the surgery
Abscess	presence of suppuration	14 days after the surgery
Edema	presence and evaluation of the post-operative edema (intra-oral and extra-oral)	3 days after the surgery
Edema	presence and evaluation of the post-operative edema (intra-oral and extra-oral)	7 days after the surgery
Edema	presence and evaluation of the post-operative edema (intra-oral and extra-oral)	14 days after the surgery
Fever	Body temperature > 37°C	3 days after the surgery
Fever	Body temperature > 37°C	7 days after the surgery
Fever	Body temperature > 37°C	14 days after the surgery
Alveolar osteitis	Presence of alveolar osteitis	3 days after the surgery
Alveolar osteitis	Presence of alveolar osteitis	7 days after the surgery
Alveolar osteitis	Presence of alveolar osteitis	14 days after the surgery
Trismus	reduction in mouth opening (measured in mm)	3 days after the surgery
Trismus	reduction in mouth opening (measured in mm)	7 days after the surgery
Trismus	reduction in mouth opening (measured in mm)	14 days after the surgery
Painkillers	Number of painkillers assumed in the first 7 days after the surgery	7 days after the surgery
bleeding on palpation	presence of bleeding on palpation	3 days after the surgery
bleeding on palpation	presence of bleeding on palpation	7 days after the surgery
bleeding on palpation	presence of bleeding on palpation	14 days after the surgery
Difficulty in chewing	Difficulty in chewing assessed by VAS (0-10)	3 days after the surgery
Difficulty in chewing	Difficulty in chewing assessed by VAS (0-10)	7 days after the surgery
Difficulty in chewing	Difficulty in chewing assessed by VAS (0-10)	14 days after the surgery
Difficulty in speaking	Difficulty in speaking assessed by VAS (0-10)	3 days after the surgery
Difficulty in speaking	Difficulty in speaking assessed by VAS (0-10)	7 days after the surgery
Difficulty in speaking	Difficulty in speaking assessed by VAS (0-10)	14 days after the surgery
Difficulty in performing oral hygiene	Difficulty in performing oral hygiene assessed by VAS (0-10)	3 days after the surgery
Difficulty in performing oral hygiene	Difficulty in performing oral hygiene assessed by VAS (0-10)	7 days after the surgery
Difficulty in performing oral hygiene	Difficulty in performing oral hygiene assessed by VAS (0-10)	14 days after the surgery
Daily routine alterations	days of stay off work	3 days after the surgery
Daily routine alterations	days of stay off work	7 days after the surgery
Daily routine alterations	days of stay off work	14 days after the surgery
Sensation of swelling	assessed by VAS (0-10)	3 days after the surgery
Sensation of swelling	assessed by VAS (0-10)	7 days after the surgery
Sensation of swelling	assessed by VAS (0-10)	14 days after the surgery
Number of disturbed-sleep nights following the extraction	Number of disturbed-sleep nights	3 days after the surgery
Number of disturbed-sleep nights following the extraction	Number of disturbed-sleep nights	7 days after the surgery
Number of disturbed-sleep nights following the extraction	Number of disturbed-sleep nights	14 days after the surgery
Abdominal pain	presence of Abdominal pain (questionnarie Y/N)	3 days after the surgery
Abdominal pain	presence of Abdominal pain (questionnarie Y/N)	7 days after the surgery
Abdominal pain	presence of Abdominal pain (questionnarie Y/N)	14 days after the surgery
Abdominal distension	presence of Abdominal pain (questionnarie Y/N)	3 days after the surgery
Abdominal distension	presence of Abdominal pain (questionnarie Y/N)	7 days after the surgery
Abdominal distension	presence of Abdominal pain (questionnarie Y/N)	14 days after the surgery
Alvus variation	presence of alvus variations (questionnarie Y/N)	3 days after the surgery
Alvus variation	presence of alvus variations (questionnarie Y/N)	7 days after the surgery
Alvus variation	presence of alvus variations (questionnarie Y/N)	14 days after the surgery
Nausea	presence of nausea (questionnarie Y/N)	3 days after the surgery
Nausea	presence of nausea (questionnarie Y/N)	7 days after the surgery
Nausea	presence of nausea (questionnarie Y/N)	14 days after the surgery
Vomit	presence of vomit (questionnarie Y/N)	3 days after the surgery
Vomit	presence of vomit (questionnarie Y/N)	7 days after the surgery
Vomit	presence of vomit (questionnarie Y/N)	14 days after the surgery
Acid reflux	presence of acid reflux (questionnarie Y/N)	3 days after the surgery
Acid reflux	presence of acid reflux (questionnarie Y/N)	7 days after the surgery
Acid reflux	presence of acid reflux (questionnarie Y/N)	14 days after the surgery
Gastric acidity	presence of gastric acidity (questionnarie Y/N)	3 days after the surgery
Gastric acidity	presence of gastric acidity (questionnarie Y/N)	7 days after the surgery
Gastric acidity	presence of gastric acidity (questionnarie Y/N)	14 days after the surgery
Gastric pain	presence of gastric pain (questionnarie Y/N)	3 days after the surgery
Gastric pain	presence of gastric pain (questionnarie Y/N)	7 days after the surgery
Gastric pain	presence of gastric pain (questionnarie Y/N)	14 days after the surgery
Loss of appetite	presence of loss of appetite (questionnarie Y/N)	3 days after the surgery
Loss of appetite	presence of loss of appetite (questionnarie Y/N)	7 days after the surgery
Loss of appetite	presence of loss of appetite (questionnarie Y/N)	14 days after the surgery

Collaborators and Investigators

• Sponsor: University of Pisa
• Investigators: Principal Investigator: Antonio Barone, Professor, University of Pisa

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2021
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: May 18, 2021
• First Submitted That Met QC Criteria: May 25, 2021
• First Posted (Actual): May 27, 2021

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Tooth Diseases; Tooth, Impacted
• Other Study ID Numbers: Antib Prob Impacted 1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No