Flapless Periodontal Regeneration Using Hyaluronic Acid Versus Enamel Matrix Derivative

NCT07339605 | Recruiting

• 1 other identifier: 2023-ODON-3018356
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to radiographically assess the effectiveness of minimally invasive non-surgical technique (MINST) combined with local administration of sodium hypochlorite gel (Perisolv®) and 1.6% cross-linked hyaluronic acid (HA, Hyadent BG®) compared to a neutral formulation of EDTA (Prefgel®) and enamel matrix derivative (EMD, Emdogain® FL) in periodontal regeneration. The main questions it aims to answer are:

• ¿Does the combination of MINST with the local administration of sodium hypochlorite gel and 1.6% cross-linked hyaluronic acid show a potential for periodontal regeneration similar to evaluating clinical and radiographic variables compared to a neutral formulation of EDTA and enamel matrix derivative?
• ¿What is the patient perception and satisfaction with the received treatment? Researchers will compare A (MINST with Perisolv® + Hyadent BG®), B (MINST with PrefGel® + Emdogain® FL) and C(MINST without any bioactive product). The sample will be distributed according to the following treatments:
• Experimental group: Scaling and root planing (SRP), MINST with Perisolv® + Hyadent BG®.
• Active comparator group: SRP, MINST with PrefGel® + Emdogain® FL.
• Control group: SRP, MINST without any bioactive product. Patients will be screened by a first visit in which they will be assigned their periodontal status. If they meet the eligibility criteria, they will be treated according to the EFP clinical guideline for periodontitis treatment: step I and step II.If the periodontal defect persists at the 12-week re-evaluation, patients will be randomised to treatment A, B or C. After the intervention, all participants will be checked weekly for the first 6 weeks to remove accumulated plaque, and every 3 months for 1 year. Periodontal parameters will be re-evaluated 6 and 12 months after periodontal regenerative intervention.

Conditions

Guided Tissue Regeneration, Periodontal / Methods; Dental Enamel Proteins* / Therapeutic Use; Alveolar Bone Loss* / Therapy; Hyaluronic Acid* / Therapeutic Use; Humans; Intrabony Defect; Flapless

Keywords

Periodontitis; Intrabony defect; Hyaluronic acid; Enamel matrix derivative; Periodontal regeneration

Outcome Measures

Primary Outcomes (1)

• Radiographic bone fill

  Depth of the intraosseous defect (B - D); and following the healing period (X - C). Bone fill (BF) will be calculated by subtracting the (X - C) measurement recorded at the 6-month and 12-month postoperative review from the depth recorded before the regenerative intervention (B - D).

  Baseline, 6 and 12 months.

Secondary Outcomes (11)

• Clinical attachment level (CAL) gain

  Baseline, 6 and 12 months.

• Gingival recession

  Baseline, 6 and 12 months.

• Probing pocket depth (PD)

  Baseline,6 and 12 months.

• Bleeding on probing

  Baseline, 6 and 12 months.

• Plaque index

  Baseline, 6 and 12 months.

Study Arms (3)

(MINST + NaOCl) + HA

EXPERIMENTAL

Procedure: Flapless instrumentation of the defect following MINST in conjuction with NaOCl and hyaluronic acid application

(MINST + EDTA) + EMD

ACTIVE COMPARATOR

Procedure: Flapless instrumentation of the defect following MINST, root conditioning with EDTA and EMD application

MINST

SHAM COMPARATOR

Procedure: Flapless instrumentation of the defect and product application simulation

Interventions

Flapless instrumentation of the defect following MINST in conjuction with NaOCl and hyaluronic acid application PROCEDURE

The NaOCL gel buffered with amino acids will be carefully injected and maintained for 60 seconds. Following this, pocket debridement will be carried out following the MINST technique. In order to allow for optimal root visualization and gain access to the intrabony defect, a microsurgical dental mirror will be used in conjunction with an atraumatic gingival retractor for a gentle lateral papilla displacement. Teeth will be instrumented until no residual calculus could be detected after a careful root evaluation with a periodontal explorer and no debris or biofilm flushed out of the pocket after irrigation. If this does not occur, the application of NaOCL, instrumentation and saline solution rinse shall be repeated until this is achieved. After irrigation, sterile gauze will be placed in the vestibule in the proximity of a selected site and a thorough drying of the site will be perfomed with air-spray. HA will be applied with a blunt tipped sterile syringe, until overflowing.

(MINST + NaOCl) + HA

Flapless instrumentation of the defect following MINST, root conditioning with EDTA and EMD application PROCEDURE

Subgingival instrumentation will be performed following the MINST technique in conjunction with a microsurgical dental mirror and an atraumatic gingival retractor without applying any product previously. Teeth will be instrumented until no residual calculus could be detected and no debris or biofilm flushed out of the pocket after irrigation with sterile saline solution. Following this, it will be dried and the root will be conditioned applying EDTA with a thin blunt tip for 2 minutes to remove the dentin mud layer from the root surfaces. Subsequently, the defect area will be carefully rinsed with water-spray and by 5-s passage of ultrasonic instrument's fine tip in the site with no contact to the root surface. A sterile gauze will be placed in the vestibule in the proximity of a selected site and a thorough drying of the site will be performed with an air-spray. Once bleeding control is achieved, EMD will be applied with a blunt tipped sterile syringe (25G), until overflowing.

(MINST + EDTA) + EMD

Flapless instrumentation of the defect and product application simulation PROCEDURE

Subgingival instrumentation will be performed following MINST and EDT+EMD or NaOCl+HA application will be simulated by inserting the manufacturer's syringes within the pocket, but the defects won't receive any adjunct.

MINST

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Periodontitis stage III or IV, grade A or B (Tonetti et al., 2017): attachment loss ≥ 5mm, radiographic bone loss extending to to the middle third and beyond, tooth loss ≥4 due to periodontitis, probing depth (PD) ≥ 6mm.
• Older adults ≥ 18 years. The number per sex shall be balanced.
• Plaque index (PI) \< 1 following initial periodontal therapy and hygiene instructions.
• Bleeding on probing (BoP) ≤ 10%.
• Only patients with optimal compliance, assessed during etiological therapy, will be selected.
• At least a 2-3 wall interproximal bone defect with a radiographically moderate or deep intrabony defect (≥3mm), PD≥ 6mm using a Williams probe on uniradicular teeth or mandibular molars without furcation involvement after non-surgical periodontal treatment.
• Vital teeth or teeth with well-performed root canal treatment.
• Absence of caries, prosthetic restoration or periapical infection in the tooth to be regenerated.
• Absence of systemic pathology.
• Negative history of pregnancy.
• Signed informed consent.
• The participant is willing and able to comply with the necessary visits for the treatments and evaluations scheduled during the clinical study.

You may not qualify if:

• The participant is pregnant, breastfeeding or plans to become pregnant in the next 6 months.
• Smoking ≥10 cigarettes/day.
• Daily alcohol intake \> 4U.
• Chronic illness or reduced mental capacity that may influence compliance with the protocol.
• Medications or drugs that alter the patient's healing or with concomitant oral manifestations that, in the opinion of the investigator, could interfere with the assessment of safety or efficacy.
• Systemic diseases that may influence treatment such as diabetes mellitus or rheumatoid disease.
• Allergies to drug compounds.
• Antibiotic intake 3 months prior to the start of the study or systemic condition requiring antibiotic coverage at the time of periodontal treatment.
• Periodontal treatment 6 months prior to the start of the study.

Sponsors & Collaborators

• University of Valencia: lead

Study Sites (1)

Clínica Odontológica de la Universidad de Valencia

Valencia, Valencia, 46010, Spain

RECRUITING

Related Publications (4)

• Steffensen B, Webert HP. Relationship between the radiographic periodontal defect angle and healing after treatment. J Periodontol. 1989 May;60(5):248-54. doi: 10.1902/jop.1989.60.5.248.

  PMID: 2738832 BACKGROUND

• Tonetti MS, Fourmousis I, Suvan J, Cortellini P, Bragger U, Lang NP; European Research Group on Periodontology (ERGOPERIO). Healing, post-operative morbidity and patient perception of outcomes following regenerative therapy of deep intrabony defects. J Clin Periodontol. 2004 Dec;31(12):1092-8. doi: 10.1111/j.1600-051X.2004.00615.x.

  PMID: 15560811 BACKGROUND

• Anoixiadou S, Parashis A, Vouros I. Enamel matrix derivative as an adjunct to minimally invasive non-surgical treatment of intrabony defects: A randomized clinical trial. J Clin Periodontol. 2022 Feb;49(2):134-143. doi: 10.1111/jcpe.13567. Epub 2021 Nov 9.

  PMID: 34708441 BACKGROUND

• Anoixiadou S, Parashis A, Vouros I. Minimally Invasive Non-Surgical Technique in the Treatment of Intrabony Defects-A Narrative Review. Dent J (Basel). 2023 Jan 11;11(1):25. doi: 10.3390/dj11010025.

  PMID: 36661562 BACKGROUND

MeSH Terms

Conditions

Alveolar Bone Loss; Periodontitis

Interventions

Edetic Acid

Condition Hierarchy (Ancestors)

Bone Resorption; Bone Diseases; Musculoskeletal Diseases; Periodontal Atrophy; Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids

Study Officials

• Andrés López Roldán

  University of Valencia

  STUDY DIRECTOR

• José Manuel Almerich Silla

  University of Valencia

  STUDY DIRECTOR

Central Study Contacts

Ferran Sánchez Benito

CONTACT

+34646411370; sanbefe@alumni.uv.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor with PhD

Study Record Dates

• First Submitted: June 30, 2025
• First Posted: January 14, 2026
• Study Start: October 26, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: January 14, 2026

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

ES (1)