Clinical trial NCT05418621: Does the Non-surgical Application of Enamel Matrix Derivative Reduce the Need of Periodontal Surgical Intervention in Subjects With Severe (Stage III) Periodontitis?
Official title: Does the Non-surgical Application of Enamel Matrix Derivative Reduce the Need of Periodontal Surgical Intervention in Subjects With Severe (Stage III) Periodontitis? A Randomized, Multicenter, Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Periodontal Diseases
Lead sponsor: University of Pisa
Sponsor class: OTHER
First posted: 2022-06-14
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Periodontal treatment relies on a sequential series of different phases that are usually incapsulated in three main phases: non-surgical treatment, surgical phase and, finally, supportive phase. Whilst, on the one hand not all patients may undergo surgical interventions, on the other hand non-surgical periodontal and supportive treatment are administered to all subjects affected by periodontitis. Both phases are constituted by closed, non-surgical, root instrumentation which is often carried out with similar techniques. Thus, non-surgical periodontal treatment (NSPT) is the one key stone of the treatment of periodontitis.

NSPT is very efficacious. A significant majority of the diseased sites are usually managed non-surgically (Graziani et al., 2017)). Moreover, bleeding on probing and symptoms are significantly decreased by NSPT. Importantly, NSPT is also capable to reduce systemic inflammation (Teeuw et al., 2014), improve glycaemic control (Sanz et al., 2018) and overall ameliorate oral health related quality of life (Graziani, Music, et al., 2019). Lastly, NSPT is cost effective as its costs are moderate and it may be performed by both dentists and hygienists.

Nevertheless, NSPT is often uncapable to solve an entire clinical case and surgical treatment is advocated as in fact the complete closure of the pockets ranges from 57 to 75% according to a follow-up of 3⁄4 months or 6/8 respectively (Solini et al., 2019). Periodontal surgery is also effective, but it is nonetheless a surgical intervention which cannot be defined as deprived of side effects (Graziani et al., 2018).

Thus, in order to improve the outcome of NSPT numerous adjunctive treatment modalities have been advocated (Braun et al., 2008; Graziani et al., 2017; Haffajee et al., 2003). Yet the objective of reducing the need for surgery has been rarely evaluated.

Recently, our group ran a trial in which enamel matrix derivatives (EMD) has been applied as non-surgical adjunct. The findings highlighted that EMD application lowers systemic inflammation, increases blood clot stability and, locally, reduces of the need for surgery by 32% compared to the control group without EMD.

Thus, a multicentre responding to the following questions:

* Flapless application of EMD reduce the need for periodontal surgery?
* Are the results stable over time?
* Can the results be generalized among different clinicians? EMD is a resorbable, implantable material and supports periodontal regeneration, which takes place over more than a year. It consists of hydrophobic enamel matrix proteins extracted from developing embryonal enamel of porcine origin in a propylene glycol alginate carrier.

The gel has a suitable viscosity to facilitate application directly onto root surfaces exposed during periodontal surgery. Once applied onto an exposed root surface the protein self assembles into an insoluble three-dimensional matrix and creates a suitable environment for selective periodontal cell migration and attachment, which re-establishes lost tooth supporting tissues. Subsequent to formation of new attachment, alveolar bone can also be regenerated due to the osteogenic capacity of the restored periodontal ligament. EMD is degraded by enzymatic processes of normal wound healing.


Eligibility criteria: Inclusion Criteria

* Accept the form of the study and signs a declaration of informed consent; understand and are willing, able and likely to comply with all study procedures and restrictions.
* Systemically healthy (according to exclusion criteria 4) participants of either genders who are attending a periodontal centre for periodontal care.
* Aged 18 or over.
* Presenting at least 20 teeth (excluded wisdom teeth).
* Being affected by generalized Periodontitis (stage III) irrespectively of the grade (Tonetti et al., 2018) i.e. presenting at least 5 mm of clinical atattachment loss at the interdental areas, radiographic bone resorption of more than 30% of the root length extending to at least the middle portion of the root, less than 5 teeth lost for periodontal reason, presenting characteristics for complexity (intrabony defects, furcation defects, moderate ridge defects)
* Bleeding on probing on at least 30% of the sites and a minimum of 4 teeth with at least one site with PPD ≥6mm

Exclusion Criteria:

* Persons incapable of responding to the questions.
* An employee of the sponsor, employee of the general dental practice, and/or a family relative of the employees mentioned above.
* Women known to be pregnant or lactating (a specific declaration form will be signed by the patient, stating the non-pregnant or lactating status).
* Persons suffering of pathologies known to affect the outcome of periodontal therapy (i.e. diabetes, osteoporosis, immunosuppression).
* Persons undergoing therapy which will may complicate adherence to protocol or showing an impact on periodontal outcome (i.e. chemotherapy and immunosuppressive treatments).
* Persons who require antibiotic coverage (following infectious endocarditis, using prosthetic cardiac valves, other pathologies).
* Persons undergoing pharmacological treatment associated with gingival hypertropia development (phenytoin, phenobarbital, lamotrigine, vigabatrin, ethosuximide, topiramate, primidone, nifedipine, amlodipine, verapamil, cyclosporine).

Persons with implant-supported restorations affected by peri-implantitis (as defined by the 2017 Classification, i.e. presence of bleeding and/or suppuration on gentle probing, probing depths of ≥6 mm, bone levels ≥3 mm apical of the most coronal portion of the intraosseous part of the implant).

* Smokers declaring to smoke more than 20 cigarettes per day.
* Persons with Body Mass Index above 29(obese subjects).
* Anyone who in the investigators' opinion is not suitable to take part in the study.
* Allergy/idiosyncrasy to anaesthesia or components of the device object of the study.
* Previous periodontal subgingival instrumentation within the previous 12 months.
* Antibiotics intake in the previous 3 months.

Primary outcomes:
measure: Resolved cases
timeFrame: 3, 6 and 12 months after treatment
Secondary outcomes:
measure: number of sites with PPD>=6mm
timeFrame: 3, 6 and 12 months after treatment
measure: changes in Full Mouth Plaque Score (FMPS)
timeFrame: 3, 6 and 12 months after treatment
measure: changes in Full Mouth Bleeding Score (FMBS)
timeFrame: 3, 6 and 12 months after treatment
measure: mean values of PPD
timeFrame: 3, 6 and 12 months after treatment
measure: mean values of recession (REC)
timeFrame: 3, 6 and 12 months after treatment
measure: mean values Clinical Attachment Level (CAL)
timeFrame: 3, 6 and 12 months after treatment
measure: Furcation involvement
timeFrame: 3, 6 and 12 months after treatment
measure: Dentine sensitivity (Schiff test)
timeFrame: 3, 6 and 12 months after treatment
measure: Oral Health Impact profile 14
timeFrame: 3, 6 and 12 months after treatment
measure: Attention Network Task
timeFrame: 3, 6 and 12 months after treatment
measure: Corsi block-tapping test
timeFrame: 3, 6 and 12 months after treatment
measure: Tower of London
timeFrame: 3, 6 and 12 months after treatment
measure: Sickness Questionnaire
timeFrame: 3, 6 and 12 months after treatment
measure: Depression Anxiety Stress Scale
timeFrame: 3, 6 and 12 months after treatment
measure: State-Trait Anxiety Inventory_ Form
timeFrame: 3, 6 and 12 months after treatment
measure: State-Trait Anxiety Inventory_ Form Y1
timeFrame: 3, 6 and 12 months after treatment
measure: Profile Mood State
timeFrame: 3, 6 and 12 months after treatment
measure: Sleep quality
timeFrame: 3, 6 and 12 months after treatment
measure: The Insomnia Severity Index
timeFrame: 3, 6 and 12 months after treatment
measure: Epworth Sleepiness Scale
timeFrame: 3, 6 and 12 months after treatment
Other outcomes:
Locations:
city: Pisa
country: Italy
facility: University Hospital of Pisa
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
Study officials:
References: