Clinical, microbiological and enzymatic evaluation after "Clean&Seal® protocol in subgingival instrumentation in severe periodontitis (C&S-STEP2)

ISRCTN	ISRCTN17852953
DOI	https://doi.org/10.1186/ISRCTN17852953
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	CE-1-2024
Sponsor	Victor Babeș University of Medicine and Pharmacy Timișoara
Funder	Investigator initiated and funded

Submission date: 23/11/2024
Registration date: 29/11/2024
Last edited: 29/11/2024

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Oral Health

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
This study aims to evaluate the effectiveness of adding cross-linked hyaluronic acid (xHyA, Hyadent BG®) to the “Clean&Seal®” protocol for treating advanced gum disease (stage III and IV periodontitis). The study will compare this new approach to using Perisolv® alone and a placebo.

Who can participate?
Adults with at least four deep gum pockets (≥5 mm) and significant bone loss (≥3 mm) who have at least 10 remaining teeth can participate. Participants must not have had recent periodontal or antibiotic treatment, certain severe dental conditions, or systemic diseases like uncontrolled diabetes. Pregnant or breastfeeding women, immunocompromised individuals, and those allergic to NaOCl are also excluded.

What does the study involve?
Participants will be randomly assigned to one of three groups: one receiving xHyA and Perisolv®, one receiving Perisolv® alone, and one receiving a placebo gel. All participants will undergo gum cleaning procedures under local anesthesia. Clinical, microbiological, and enzymatic parameters will be measured at the start and three months after treatment.

What are the possible benefits and risks of participating?
Participants may benefit from improved gum health and reduced inflammation. However, there are risks associated with any dental procedure, including discomfort and potential allergic reactions.

Where is the study run from?
The study is conducted at the University Clinic of Periodontology, Victor Babeș University of Medicine and Pharmacy, Timișoara (Romania)

When is the study starting and how long is it expected to run for?
November 2024 to July 2027

Who is funding the study?
Investigator initiated and funded

Who is the main contact?
Dr Elena Catana, elena.catana@umft.ro

Contact information

Dr Elena Catana
Public, Scientific, Principal investigator

Str. Martir Constantin Valceanu nr.18
Timișoara
300291
Romania

ORCID ID	0009-0009-2711-7691
Phone	+40 745649445
Email	elena.catana@umft.ro

Study information

Primary study design	Interventional
Study design	Interventional randomized single-blinded clinical trial with 3 months follow-up
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Clinical, microbiological and enzymatic evaluation of hyaluronic acid used in the "Clean&Seal®" protocol in step 2 of the therapy of the severe and the advanced periodontitis
Study acronym	C&S-STEP2
Study objectives	Clean&seal protocol in subgingival instrumentation in step 2 of periodontal treatment results in better clinical, microbiological and enzymatic outcomes than Perisolv alone and placebo.
Ethics approval(s)	Approved 04/11/2024, The Committee on Research Ethics of the Victor Babes University of Medicine and Pharmacy Timisoara (Pta Eftimie Murgu 2A, Timisoara, 300041, Romania; +40-256204400; cecs@umft.ro), ref: 54/04.11.2024
Health condition(s) or problem(s) studied	Severe and advanced periodontitis
Intervention	Participants will be randomly assigned to one of three groups: test group 1 will receive treatment with hyaluronic acid and hypochlorite gel; test group 2 will use hypochlorite gel alone, and group 3 (control) will receive a placebo gel. Subgingival instrumentation will be performed under local anesthesia using ultrasonic and manual instruments, with protocol-specific gel applications preceding the instrumentation. Three months post-treatment, participants will undergo reevaluation of clinical, microbiological, histological and enzymatic parameters. Data will be analyzed using appropriate statistical methods.
Intervention type	Procedure/Surgery
Primary outcome measure(s)	Probing depth (PD) is measured using a periodontal probe (PCP-UNC 15, Hu-Friedy Manufacturing Co., Chicago, IL, USA) at baseline and 3 months post-therapy
Key secondary outcome measure(s)	1. Full mouth plaque score (FMPS) is measured using a periodontal probe (PCP-UNC 15, Hu-Friedy Manufacturing Co., Chicago, IL, USA) at baseline and 3 months post-therapy 2. Full mouth bleeding score (FMBS) is measured using a periodontal probe (PCP-UNC 15, Hu-Friedy Manufacturing Co., Chicago, IL, USA) at baseline and 3 months post-therapy 3. Clinical attachment loss (CAL) is measured using a periodontal probe (PCP-UNC 15, Hu-Friedy Manufacturing Co., Chicago, IL, USA) at baseline and 3 months post-therapy 4. Gingival recession (GR) is measured using a periodontal probe (PCP-UNC 15, Hu-Friedy Manufacturing Co., Chicago, IL, USA) at baseline and 3 months post-therapy 5. Bacterial pathogens are quantitatively evaluated using PCR testing at baseline and 3 months post-therapy from sites with the highest probing pocket depth (PPD) 6. MMP-8 and IL-1 levels are analyzed using dento-ELISA immunoassay at the University Department of Biochemistry at UMVBT from gingival crevicular fluid samples collected at baseline and 3 months post-treatment from the site with the deepest probing depth 7. Inflammatory status is assessed histologically by analyzing gingival biopsies harvested using micro-tissue punches at baseline and 3 months post-treatment to determine the amount of inflammatory cells and describe the characteristics of intercellular substance in relation to the clean and seal protocol
Completion date	30/07/2027

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	65 Years
Sex	All
Target sample size at registration	60
Key inclusion criteria	1. Adult patients aged 18 - 65 years 2. At least 10 remaining teeth in oral cavity 3. Presence of minimum 4 sites with periodontal pockets ≥5mm, with positive BOP, radiographic bone loss ≥3mm
Key exclusion criteria	1. Molars with furcation involvement class II or III 2. Endodontic lesions 3. Severe occlusal dysfunction 4. Antibiotic treatment 3 months prior to the start of the trial or during study participation 5. Systemic diseases that may influence the outcome of periodontal therapy (e.g., uncontrolled diabetes prior to or during study participation) 6. Immunocompromised patients 7. Allergic patients to NaOCl 8. Pregnant and breastfeeding women
Date of first enrolment	15/11/2024
Date of final enrolment	01/01/2027

Locations

Countries of recruitment

Romania

Study participating centre

University Clinic of Periodontology, Victor Babes University of Medicine Timisoara

9, Bv. Revolutiei din 1989
Timisoara
300041
Romania

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated and/or analysed during the current study will be available upon request from Dr Elena Catana, elena.catana@umft.ro

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

25/11/2024: Trial's existence confirmed by The Committee on Research Ethics of the Victor Babes University of Medicine and Pharmacy Timisoara.