Clinical trial NCT05498012: CBD Effects on Periodontal Health of Patients With Chronic Periodontitis
Official title: Cannabidiol Effects on Chronic Periodontitis: Monocentric, Randomized, Interventional and Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Periodontitis
Keywords: Periodontitis
Phytocannabinoid
Cannabidiol
Dental gel
Oral microbiota
Inflammation
Lead sponsor: Palacky University
Sponsor class: OTHER
Collaborators: name: CB21 Pharma Ltd.
First posted: 2022-08-11
Enrollment: 90
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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

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:

1. 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.
2. 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.
3. 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).
4. 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).
5. 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.

Eligibility criteria: 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

Primary outcomes:
measure: Effect of cannabidiol on periodontal health (Russell's periodontal index ) of patients with chronic periodontitis
timeFrame: Baseline (0 day) and 67 days
measure: Effect of cannabidiol on periodontal health (plaque/gingival indices) of patients with chronic periodontitis
timeFrame: Baseline (0 day) and 67 days
measure: Effect of cannabidiol on periodontal health (bleeding) of patients with chronic periodontitis
timeFrame: Baseline (0 day) and 67 days
measure: Effect of cannabidiol on periodontal health (modified gingival index) of patients with chronic periodontitis
timeFrame: Baseline (0 day) and 67 days
Secondary outcomes:
measure: Effect of cannabidiol on oral microbiota
timeFrame: Baseline (0 day) and 67 days
measure: Cannabidiol oral cavity side effects and gingival immune system
timeFrame: Baseline (0 day) and 37 days
Other outcomes:
Locations:
city: Olomouc
country: Czechia
facility: Department of Dentistry, Olomouc University Hospital
state: Czech Republic
Study officials:
References:
citation: Stahl V, Vasudevan K. Comparison of Efficacy of Cannabinoids versus Commercial Oral Care Products in Reducing Bacterial Content from Dental Plaque: A Preliminary Observation. Cureus. 2020 Jan 29;12(1):e6809. doi: 10.7759/cureus.6809.
citation: Vasudevan K, Stahl V. Cannabinoids infused mouthwash products are as effective as chlorhexidine on inhibition of total-culturable bacterial content in dental plaque samples. J Cannabis Res. 2020 Jun 23;2(1):20. doi: 10.1186/s42238-020-00027-z.
citation: Lowe H, Toyang N, Steele B, Bryant J, Ngwa W, Nedamat K. The Current and Potential Application of Medicinal Cannabis Products in Dentistry. Dent J (Basel). 2021 Sep 10;9(9):106. doi: 10.3390/dj9090106.
citation: RUSSELL AL. A system of classification and scoring for prevalence surveys of periodontal disease. J Dent Res. 1956 Jun;35(3):350-9. doi: 10.1177/00220345560350030401. No abstract available.
citation: Loe H. The Gingival Index, the Plaque Index and the Retention Index Systems. J Periodontol. 1967 Nov-Dec;38(6):Suppl:610-6. doi: 10.1902/jop.1967.38.6.610. No abstract available.
citation: Ainamo J, Bay I. Problems and proposals for recording gingivitis and plaque. Int Dent J. 1975 Dec;25(4):229-35.
citation: Lobene RR, Weatherford T, Ross NM, Lamm RA, Menaker L. A modified gingival index for use in clinical trials. Clin Prev Dent. 1986 Jan-Feb;8(1):3-6. No abstract available.
citation: Jirasek P, Jusku A, Simanek V, Frankova J, Storch J, Vacek J. Cannabidiol and periodontal inflammatory disease: A critical assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2022 May;166(2):155-160. doi: 10.5507/bp.2022.012. Epub 2022 Mar 21.