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Hyaluronic Acid for Residual Periodontal Pockets Adjunctive Treatment

Primary Purpose

Periodontitis

Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Hyaluronic Acid
Lidocain
Sponsored by
University of Roma La Sapienza
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Periodontitis focused on measuring hyaluronic acid, periodontitis, periodontal therapy, residual pockets

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • at least 18 years of age
  • systemically healthy,
  • smoking less than 10 cigarettes/day
  • having been treated for periodontitis but with at least one single residual pocket of 5-9mm of depth located in the anterior area (incisors and canines)
  • full-mouth bleeding score (FMBS)
  • full-mouth plaque score (FMPS) less than 20%
  • showing a good compliance to oral hygiene instructions

Exclusion Criteria:

  • were pregnancy/lactation
  • use of antibiotics in the last 3 months for a period of two weeks or more
  • use of drugs causing gingival hyperplasia
  • use of corticosteroids or anti-inflammatory drugs for a period of two weeks or more
  • presence of diseases knowing to influence the wound healing/tissue response
  • thyroid or pituitary gland malfunction or abnormal hormonal levels
  • hyaluronic acid contraindications
  • subjects under anticoagulant treatment
  • use of systematic antibiotics for endocarditis prophylaxis
  • radiation therapy in head and neck area
  • use of bisphosphonate drugs prescribed for patients with osteoarthritis
  • tooth mobility.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Hyaluronic acid

    Lidocaine

    Arm Description

    After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of hyaluronic acid gel . This adjunctive treatment was performed at baseline and at the 3 months control.

    After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of anesthetic. This adjunctive treatment was performed at baseline and at the 3 months control.

    Outcomes

    Primary Outcome Measures

    PD (change is being assessed)
    probing depth (PD) measured with periodontal probe in mm

    Secondary Outcome Measures

    BoP(change is being assessed)
    bleeding on probing measured after probing as dichotomous parameter
    Dental plaque(change is being assessed)
    dental plaque measured with periodontal probe as dichotomous parameter
    REC(change is being assessed)
    gingival recession measured with periodontal probe in mm

    Full Information

    First Posted
    December 14, 2020
    Last Updated
    January 7, 2021
    Sponsor
    University of Roma La Sapienza
    Collaborators
    University of Rijeka, University of Zagreb, Jagiellonian University, Medical University of Sofia, University of Bern, Plovdiv Medical University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04702334
    Brief Title
    Hyaluronic Acid for Residual Periodontal Pockets Adjunctive Treatment
    Official Title
    Adjunctive Treatment of Residual Periodontal Pockets Using a Hyaluronic Acid-based Gel: A 12-month Multicenter Randomized Triple Blinded Clinical Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2021
    Overall Recruitment Status
    Completed
    Study Start Date
    January 2016 (Actual)
    Primary Completion Date
    November 2018 (Actual)
    Study Completion Date
    November 2018 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of Roma La Sapienza
    Collaborators
    University of Rijeka, University of Zagreb, Jagiellonian University, Medical University of Sofia, University of Bern, Plovdiv Medical University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Objective: To evaluate the adjunctive effect of hyaluronic acid (HA) gel in the treatment of residual periodontal pockets over a 12-month period. Materials and Methods: Periodontal patients enrolled in maintenance and presenting at least one periodontal pocket 5-9 mm of depth in the anterior area were recruited from six university-based centers. Each patient was randomly assigned to control treatment with professional mechanical plaque removal (PMPR) and local placebo application or test treatment with the adjunctive use of HA to PMPR. Clinical parameters [i.e. probing depth (PD), bleeding on probing (BoP), plaque score, recession (REC), and clinical attachment loss (CAL)] and microbiological samples for the investigation of the total bacterial count (TBC) and presence of specific bacterial strains (Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum) were taken at baseline and every 3 months, until study termination. PD was determined as the primary outcome variable.
    Detailed Description
    Population A total of 144 patients were enrolled from 6 university clinical centers (Sapienza University of Rome, Department of Periodontology, Rome, Italy ; University of Rijeka, School of Dental Medicine, Rijeka, Croatia; University of Zagreb, Department of Periodontology, Zagreb, Croatia; Jagiellonian University, Dental Institute, Krakow, Poland; Medical University of Sofia, Faculty of Dentistry, Sofia, Bulgaria; Medical University of Plovdiv, Faculty of Dentistry, Plovdiv, Bulgaria). The extension in time from patient recruitment to end of the protocol was January 2016 to November 2018. The sample size was determined considering the patient level as statistical unit and probing depth (PD) as the primary outcome measure. In order to detect a mean difference of 1 mm of PD between groups with a standard deviation of 1 mm, maintaining a power of 85%, a significance level (alpha) of 0.05 and a drop-out of 25%, 12 participants per group in each center were required. The ethical committees of each center approved the protocol of this study. The protocol followed the ethical principles of Helsinki Declaration on the good conduct of clinical trials. All patients were thoroughly informed on the treatment details and on the possibility of being excluded from the study if missing any of the 3 months follow-up appointments or showing poor compliance in general. After verbally accepting the conditions of the protocol, patients signed the informed consent prior to study initiation. Figure 1 shows step by step the study protocol that each patient followed. Study design, randomization, allocation concealment and blinding This study was projected as a controlled randomized multicenter triple blinded 12-month clinical trial to compare the treatment of residual periodontal pockets using standard non-surgical mechanical debridement with and without hyaluronic acid gel. The detailed description of the treatment and evaluation is described in the following paragraphs. The operators were trained and calibrated on treatment application and on PD measurement prior to study initiation. A preliminary session of PD measurements on 3 periodontal patients revealed an intra-class correlation coefficient ≥ 0.75 for each operator and among different operators. An electronic web-based online randomization system was used for this study including a simulation version of the software for operator training prior to trial initiation. This system had been approved by the Austrian Agency for Health and Food Safety (AGES). The system parameters were set to randomization block size of 4, treatment code selection to random, using 24 treatment codes per center, and using minimization method. Centers were included as a factor for randomization process with assignment probability of 0,125 for each center (8 centers x 0,125 = 1.0) as the randomization ratio was 1:1 corresponding to treatment/ control allocation ratio. Each operator had a username and password to perform the randomization process for each patient. An accurate audit trail showed each user log entry consisting of login-ID, center number, investigator name, event code, date, and time of which the event occurred. The system had trial specific features (role-based access control) where trial coordinators could manage each user assigned specific role determining the user's access rights. For the present study, the investigators role was to randomize without the ability to view the trial design or randomization design. The access to full control, view randomizations, un-blind randomization, was only granted to the independent trial coordinator. Furthermore, the system provided high flexibility and security including verification for the personal email for each investigator to guarantee that each investigator will perform the randomization personally, setting a pre-defined randomization limit, the possibility to include multiple users under each center, and an effective email notification and confirmation upon each randomization performed. All transactions on the system were logged and an audit trail could be analyzed at any time by the trial monitor. The allocation concealment was done by means of independent computerized randomization sequence process which can only be accessed by the independent trial coordinator. The investigators were provided with online login and were instructed to perform the randomization only after finishing the baseline measurements and mechanical debridement of selected tooth. To ensure that, investigators were requested to write down the exact time on provided case report forms upon finishing debridement. The computerized time stamp, electronic logs of sent allocation served as a method for monitoring allocation concealment. Furthermore, having the randomization as parallel with stratified (stratification by center) permuted blocks, served as a second layer of preventing knowledge of upcoming patient's assignment. Clinical operators were kept blind until the moment of adjunctive treatment application allocated by the randomizer. Patients remained blinded during the entire follow-up. Microbiological evaluation and statistical interpretation of the results were made blinded on the treatment performed. Treatment procedure Each center was provided with the same amount of HA , Eppendorf tubes, curettes , tooth paste , tooth brushes ** and interdental brushesǁ. Patients were instructed to use the modified Bass technique for brushing twice daily with the provided toothpaste free of chlorhexidine and to use the interdental brush once daily. They were instructed not to use any type of mouthwash. All patients underwent a full mouth debridement completed within 48h in two consecutive visits. The debridement was performed using ultrasonic devices followed by curettes for all pockets of more than 4 mm. The ultrasonic treatment was repeated to ensure all surfaces were clean, followed by polishing. At reevaluation, a tooth entering the inclusion criteria was selected. After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of hyaluronic acid gel for the test group and local administration of anesthetic for the control group. The tip of blunt application needle mounted on the syringe containing HA was delicately inserted in the pocket until resistance was felt. The injection was performed until the remnants started getting out of the pocket. Patients were advised not to drink or eat for 2 hours. This adjunctive treatment was performed at baseline and at the 3 months control. For both groups cleaning of supragingival tooth deposits and polishing was repeated at 3, 6, 9, and 12 months. Statistical analysis Numerical variables were reported as median (IQR) while categorical variables were reported as frequency (percentage). McNemar test was used to test for differences in proportions between time points within groups and Chi-squared test was used for differences in proportions between groups. For numerical variables, time-points differences were assessed with the Kruskal-Wallis test and pairwise comparisons were performed with Mann-Whitney U test and Wilcoxon signed rank test (for unrelated and related measurements respectively). Holms correction was used to adjust for multiple comparisons. A significance level of 0.05 was used for all statistical tests. All the analytical tests were performed using the statistical software R (version 3.6.0).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Periodontitis
    Keywords
    hyaluronic acid, periodontitis, periodontal therapy, residual pockets

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    All patients underwent a full mouth debridement completed within 48h in two consecutive visits. At reevaluation, a tooth entering the inclusion criteria was selected. After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of hyaluronic acid gel for the test group and local administration of anesthetic for the control group. The tip of blunt application needle mounted on the syringe containing HA was delicately inserted in the pocket until resistance was felt. The injection was performed until the remnants started getting out of the pocket. Patients were advised not to drink or eat for 2 hours. This adjunctive treatment was performed at baseline and at the 3 months control. For both groups cleaning of supragingival tooth deposits and polishing was repeated at 3, 6, 9, and 12 months.
    Masking
    ParticipantCare Provider
    Masking Description
    Clinical operators were kept blind until the moment of adjunctive treatment application allocated by the randomizer. Patients remained blinded during the entire follow-up. Microbiological evaluation and statistical interpretation of the results were made blinded on the treatment performed.
    Allocation
    Randomized
    Enrollment
    144 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Hyaluronic acid
    Arm Type
    Experimental
    Arm Description
    After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of hyaluronic acid gel . This adjunctive treatment was performed at baseline and at the 3 months control.
    Arm Title
    Lidocaine
    Arm Type
    Placebo Comparator
    Arm Description
    After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of anesthetic. This adjunctive treatment was performed at baseline and at the 3 months control.
    Intervention Type
    Drug
    Intervention Name(s)
    Hyaluronic Acid
    Other Intervention Name(s)
    Hyadent® BG, BioScience GmbH, Germany
    Intervention Description
    After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of hyaluronic acid gel for the test group . The tip of blunt application needle mounted on the syringe containing HA was delicately inserted in the pocket until resistance was felt. The injection was performed until the remnants started getting out of the pocket.This adjunctive treatment was performed at baseline and at the 3 months control.
    Intervention Type
    Drug
    Intervention Name(s)
    Lidocain
    Other Intervention Name(s)
    Xylocaine® Dental
    Intervention Description
    After application of local anesthetic, removal of plaque and polishing of the tooth surfaces was performed followed by the local administration of anesthetic for the control group. The tip of blunt application needle mounted on the syringe containing HA was delicately inserted in the pocket until resistance was felt. The injection was performed until the remnants started getting out of the pocket.This adjunctive treatment was performed at baseline and at the 3 months control.
    Primary Outcome Measure Information:
    Title
    PD (change is being assessed)
    Description
    probing depth (PD) measured with periodontal probe in mm
    Time Frame
    at baseline and at 3, 6, 9, and 12 months after being treated
    Secondary Outcome Measure Information:
    Title
    BoP(change is being assessed)
    Description
    bleeding on probing measured after probing as dichotomous parameter
    Time Frame
    at baseline and at 3, 6, 9, and 12 months after being treated
    Title
    Dental plaque(change is being assessed)
    Description
    dental plaque measured with periodontal probe as dichotomous parameter
    Time Frame
    at baseline and at 3, 6, 9, and 12 months after being treated
    Title
    REC(change is being assessed)
    Description
    gingival recession measured with periodontal probe in mm
    Time Frame
    at baseline and at 3, 6, 9, and 12 months after being treated
    Other Pre-specified Outcome Measures:
    Title
    microbiological measurements(change is being assessed)
    Description
    Total bacterial count, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum
    Time Frame
    at baseline and at 3, 6, 9, and 12 months after being treated

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: at least 18 years of age systemically healthy, smoking less than 10 cigarettes/day having been treated for periodontitis but with at least one single residual pocket of 5-9mm of depth located in the anterior area (incisors and canines) full-mouth bleeding score (FMBS) full-mouth plaque score (FMPS) less than 20% showing a good compliance to oral hygiene instructions Exclusion Criteria: were pregnancy/lactation use of antibiotics in the last 3 months for a period of two weeks or more use of drugs causing gingival hyperplasia use of corticosteroids or anti-inflammatory drugs for a period of two weeks or more presence of diseases knowing to influence the wound healing/tissue response thyroid or pituitary gland malfunction or abnormal hormonal levels hyaluronic acid contraindications subjects under anticoagulant treatment use of systematic antibiotics for endocarditis prophylaxis radiation therapy in head and neck area use of bisphosphonate drugs prescribed for patients with osteoarthritis tooth mobility.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Blerina Zeza, DDS,MS,PhD
    Organizational Affiliation
    University of Rome
    Official's Role
    Study Director
    First Name & Middle Initial & Last Name & Degree
    Andrea Pilloni, DDS,Msc
    Organizational Affiliation
    University of Rome
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Only IPD that underlie results in the publication
    IPD Sharing Time Frame
    once it is published
    IPD Sharing Access Criteria
    depending on the journal that could accept the paper

    Learn more about this trial

    Hyaluronic Acid for Residual Periodontal Pockets Adjunctive Treatment

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