Stoma-CBD: CBD Effects on Periodontal Health of Patients With Chronic Periodontitis

Sponsor

Palacky University (Other)

Overall Status

Completed

CT.gov ID

NCT05498012

Collaborator

CB21 Pharma Ltd. (Other)

Enrollment

Location

Arms

14.9

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The suppression of chronic periodontitis after application of dental gel and toothpaste containing cannabidiol (CBD) will be evaluated.

Condition or Disease	Intervention/Treatment	Phase
Chronic Periodontitis	Combination Product: placebo dental gel, placebo toothpaste Combination Product: Cannabidiol dental gel, Cannabidiol toothpaste Combination Product: Placebo toothpaste, Corsodyl dental gel	Phase 1/Phase 2

Detailed Description

Current state of the art: Non-psychotropic cannabinoids (especially cannabidiol, CBD) are used as drugs and anti-inflammatory components in a number of medical devices. Their use in dentistry (in the form of a full-fledged clinical trial) has not yet been tested. Several pharmacological activities have recently been demonstrated for CBD. Its anti-inflammatory and anti-bacterial action on oral cavity tissues may be beneficial for patients after dental surgery or in patients with periodontal problems. To date, the only registered clinical trial with CBD as the active ingredient in toothpaste and mouthwash was conducted at Swinburne University of Technology in Melbourne (ANZCTR 2019). The products are tested on men aged from 18 to 30 years with chronic gingivitis diagnosis.

Study description: The aim of the study is to evaluate the effect of CBD on the periodontal disease. The study will be conducted as a 67-day, monocentric, randomized, interventional, and placebo-controlled clinical trial. The effect of dental gel and toothpaste containing CBD will be tested. The main evaluated criteria will include a series of periodontal and hygienic indices. The study will be carried out in accordance with the Helsinki Declaration of Human Rights and CONSORT rules.

Recruitment and study design: Recruitment (men and women, age 35-65) will be followed by several visits:

At the first visit (0 day), patients who meet the inclusion criteria will be documented via the set of periodontal, gingival and hygienic indices, microbiological sampling, removal of supra/sub-gingival plaque and calculus will be done. Furthermore, a gingival sample will be collected for histopathological examination and, hygienic instructions will take place.
At the second visit (day 7), the patients will be checked for proper oral hygiene, patient's periodontal health will be assessed via the set of periodontal, gingival and hygienic indices and CBD dental gel (or identical placebo without CBD) will be applied (5 min exposure). Toothpastes containing CBD or placebo will be handed over. The patients will use the toothpastes to substitute their normal dental hygiene for the duration of the study.
At the third visit (day 22), patient's periodontal health will be assessed via the set of periodontal, gingival and hygienic indices and CBD dental gel (or identical placebo without CBD) will be applied (5 min exposure).
At the fourth visit (day 37), in case of termination of therapy, gingival samples will be collected for histopathological examination. Patient's periodontal health will be assessed via the set of periodontal, gingival and hygienic indices. A microbiological sample will be collected as well. If the therapy is continued, hygienic re-instruction and repeated application of CBD gel will take place (5 min exposure).
During the last visit, patient's periodontal health will be assessed via the set of periodontal, gingival and hygienic indices. Microbiological sampling will be performed. The total duration of the study was set at 67 days.

Evaluation of study results: The clinical study will be evaluated based on measurement of Russell's periodontal index, plaque index and gingival index, gingival bleeding index and modified gingival index. Statistical analysis will be performed in SPSS or STATA software. Furthermore, microbiological sampling and gingival samples for histopathological examination (count of plasmocytes, T-lymphocytes, B-lymphocytes and macrophages in interdental papilla) will be collected.

Study Design

Study Type:

Interventional

Actual Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Supportive Care

Official Title:

Cannabidiol Effects on Chronic Periodontitis: Monocentric, Randomized, Interventional and Placebo-controlled Study

Actual Study Start Date :

Nov 5, 2020

Actual Primary Completion Date :

Jan 27, 2022

Actual Study Completion Date :

Feb 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo group Dental gel applied by dentist after oral hygiene (no cannabidiol). Toothpaste for daily use as needed for patients (no cannabidiol).	Combination Product: placebo dental gel, placebo toothpaste Placebo dental gel applied by dentist after oral hygiene; without cannabidiol. Placebo toothpaste; without cannabidiol. For daily use by patient.
Experimental: CBD group Dental CBD (cannabidiol) gel applied by dentist after oral hygiene. CBD toothpaste for daily use as needed for patients.	Combination Product: Cannabidiol dental gel, Cannabidiol toothpaste Cannabidiol dental gel applied by dentist after oral hygiene; containing 1 % (w/w) cannabidiol. Cannabidiol toothpaste; containing 1 % (w/w) cannabidiol. For daily use by patient.
Active Comparator: Corsodyl group Corsodyl dental gel applied by dentist after oral hygiene. Toothpaste for daily use as needed for patients (no cannabidiol).	Combination Product: Placebo toothpaste, Corsodyl dental gel Corsodyl dental gel; containing 1 % (w/w) chlorhexidini digluconatis applied by dentist after oral hygiene. Placebo toothpaste; without cannabidiol. For daily use by patient.

Arm

Intervention/Treatment

Placebo Comparator: Placebo group

Dental gel applied by dentist after oral hygiene (no cannabidiol). Toothpaste for daily use as needed for patients (no cannabidiol).

Combination Product: placebo dental gel, placebo toothpaste

Placebo dental gel applied by dentist after oral hygiene; without cannabidiol. Placebo toothpaste; without cannabidiol. For daily use by patient.

Experimental: CBD group

Dental CBD (cannabidiol) gel applied by dentist after oral hygiene. CBD toothpaste for daily use as needed for patients.

Combination Product: Cannabidiol dental gel, Cannabidiol toothpaste

Cannabidiol dental gel applied by dentist after oral hygiene; containing 1 % (w/w) cannabidiol. Cannabidiol toothpaste; containing 1 % (w/w) cannabidiol. For daily use by patient.

Active Comparator: Corsodyl group

Corsodyl dental gel applied by dentist after oral hygiene. Toothpaste for daily use as needed for patients (no cannabidiol).

Combination Product: Placebo toothpaste, Corsodyl dental gel

Corsodyl dental gel; containing 1 % (w/w) chlorhexidini digluconatis applied by dentist after oral hygiene. Placebo toothpaste; without cannabidiol. For daily use by patient.

Outcome Measures

Primary Outcome Measures

Effect of cannabidiol on periodontal health (Russell's periodontal index ) of patients with chronic periodontitis [Baseline (0 day) and 67 days]
Subjects will undergo the measurement of periodontal index according to A.L. Russell. Data will be collected based on five possible clinical conditions corresponding to the following scoring: Score 0-0.2 (clinical normally supportive tissue) Score 0.3-0.9 (simple gingivitis) Score 1.0-1.9 (beginning destructive periodontal disease) Score 2.0-4.9 (established destructive periodontal disease) Score 5.0-8.0 (terminal disease) Change = (Score after 67 days - Baseline score)
Effect of cannabidiol on periodontal health (plaque/gingival indices) of patients with chronic periodontitis [Baseline (0 day) and 67 days]
Subjects will undergo the measurement of plaque/gingival indeces according to H. Löe. Data will be collected based on clinical conditions corresponding to the following scoring systems: Plaque index: Score 0 (excellent) Score 0.1-0.9 (good) Score 1.0-1.9 (fair) Score 2.0-3.0 (poor) Gingival index: Score 0.1-1 (mild inflammation) Score 1.1-2 (moderate inflammation) Score 2.1-3 (severe inflammation) Change = (Score after 67 days - Baseline score)
Effect of cannabidiol on periodontal health (bleeding) of patients with chronic periodontitis [Baseline (0 day) and 67 days]
Subjects will undergo the measurement of gingival bleeding index according to J. Ainamo. Data will be collected based on clinical conditions corresponding to the score related to percentage of bleeding sites: Score 0-1 = 0 %-100 % (bleeding) Change = (Score after 67 days - Baseline score)
Effect of cannabidiol on periodontal health (modified gingival index) of patients with chronic periodontitis [Baseline (0 day) and 67 days]
Subjects will undergo the measurement of modified gingival index according to R.R. Lobene. Data will be collected based on clinical conditions corresponding to the scoring: Score 0.1-1 (mild inflammation) Score 1.1-2 (moderate inflammation) Score 2.1-3 (severe inflammation) Change = (Score after 67 days - Baseline score)

Secondary Outcome Measures

Effect of cannabidiol on oral microbiota [Baseline (0 day) and 67 days]
Evaluation of cannabidiol effect on the composition of periopathogenic bacteria (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia (Bacteroides forsythus), Treponema denticola, Parvimonas micra, Prevotella intermedia, Fusobacterium nucleatum, Campylobacter rectus, Eubacterium nodatum, Eikenella corrodens, Capnocytophaga sp.) in oral cavity using 16s rRNA sequencing protocol. Semi-quantitative evaluation of bacterial count: Code (-) = no bacteria Code (+) = mild infection Code (++) = moderate infection Code (+++) = severe infection Change = (count after 67 days - Baseline count)
Cannabidiol oral cavity side effects and gingival immune system [Baseline (0 day) and 37 days]
Evaluation of side effects of cannabidiol based on physical examination (photodocumentation) of oral cavity and histopathological analysis of gingiva (interdental papilla), count of plasmocytes, T-lymphocytes, B-lymphocytes and macrophages) will also be performed. Finally, the inflammatory grade according to the number of inflammatory cells per field of view will be evaluated. The intensity of inflammatory response will be classified as: minimal inflammation (number of immune cells up to 60 per field of view), mild inflammation (number of analyzed immune cells in the range of 61 to 100), moderate inflammation (focally confluent sheets of inflammatory cells in the range of 101 to 200), severe inflammation (confluent sheets of inflammatory cells in number more than 200). Change = (count after 37 days - Baseline count)

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Chronic periodontitis
Age 35-65 years
Number of native teeth 16 or 16+
Signed informed consent
Without physical or mental impairment

Exclusion Criteria:

Chronic diseases (diabetes mellitus, oncological diseases)
Increased bleeding (medications - anticoagulants, antiplatelet agents, bleeding diathesis)
Pregnant and lactating women
Tabacco smokers
Users of cannabis or cannabis products
ATB treatment during the last 3 months
Patient with removable prosthesis
Parallel participation in another clinical trial