PeriodontitisNCT05403164
Epithelial Mesenchymal Transition and Periodontitis
An observational study of Periodontitis and Periodontal Diseases, run by University of Baghdad at 1 site in Iraq.
Trial summary
Periodontitis is a chronic inflammatory disease results is destruction of the attachment apparatus of the teeth and ultimately tooth loss. Epithelial-mesenchymal transition (EMT) is a process comprises of series of events that influence a polarized epithelial cell to undergo molecular/morphological changes leading to… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Periodontitis, Periodontal Diseases, Epithelial-Mesenchymal Transition
- What is being tested?
- Modified Widman flap and Gingivectomy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- How many people
- 80 participants
- Where
- 1 siteIraq
- Study dates
- 12 Jul 2021to 30 Aug 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Participants involved in this study are recruited from the patient attending to the Department of Periodontics, College of Dentistry, University of Baghdad. Those patients were treated non-surgically by the residents in the department. Primary endpoint of is assessed three months after completion of non-surgical therapy. Patients with persistent pockets at posterior teeth indicated for modified Widman flap are included in the study. Prior to enrollment, aims and details of the study are clearly explained to the patients who then asked to sign the consent form. All procedures in this study followed Helsinki declaration and its later amendments for conducting human researches.
Who may be able to join
- Diagnosed with generalized periodontitis, unstable, no risk factor
- Selected site should be indicated for surgical treatment by modified Widman flap in posterior area and these sites must exhibit periodontal pockets ≥ 5mm or pockets ≥ 4mm with BOP
- Plaque index score < 10%
- Never smoker or former smoker
- Not currently using systemic or local antimicrobials (at least in the last three months)
- Not currently using a mouth rinse
- In good general health with no evidence of any systemic disease
- Willing to consent
Who cannot join
- Have history of systemic disease e.g., diabetes mellitus
- Periodontal treatment in the last 6 months
- Current participation in other clinical trials
- Pregnant women
- Current smoker
- Not willing to sign the consent form
Trial locations and contacts
1 site in 1 country.
Iraq1 site, 1 recruiting
- Recruiting
College of Dentistry, University of Baghdad
Baghdad
Bashar H Abdullah, PhD, +964 7739201860, drbashar69@yahoo.com
Ali A Abdulkareem, PhD
About this study
Official title: The Role of Epithelial-mesenchymal Transition in Patients With Periodontitis (An Immunohistochemistry Study)
Periodontitis is a chronic inflammatory disease results is destruction of the attachment apparatus of the teeth and ultimately tooth loss.
Epithelial-mesenchymal transition (EMT) is a process comprises of series of events that influence a polarized epithelial cell to undergo molecular/morphological changes leading to acquisition of mesenchymal cell phenotype. This process is responsible for suppressing epithelial-phenotype and it is known to be triggered by chronic exposure to inflammatory cytokines, Gram-negative bacteria, hypoxia, smoking, and hyperglycemia.
Both periodontitis and EMT share common risk factors/promoters; however, the role of EMT in the pathogenesis of periodontitis is not fully elucidated yet. Potential induction of EMT within periodontal pockets may disrupt epithelial barrier thus facilitating invasion of pathogenic periodontal pathogens to deeper tissues resulting in further tissue breakdown and non-resolving periodontal lesion.
Read the detailed description
Periodontitis is a highly prevalent inflammatory disease affecting the attachment apparatus of the teeth, leading to progressive destruction of periodontal ligament and resorption of alveolar bone which if not treated, at early stages, it will lead to tooth loss. It is characterised by presence of a wide diversity of pathogenic bacteria, specifically Gram-negative anaerobes, that possess range of virulence factors responsible for triggering intense inflammatory response. Although this response is protective in nature; however, it leads to undesirable collateral damage to the surrounding tissues that is further aggravated by the aberrant immune response of the host.
Epithelial-mesenchymal transition (EMT) is a process comprises of series of events that influence a polarized epithelial cell to undergo molecular/morphological changes leading to acquisition of mesenchymal cell phenotype. EMT is modulated by range of regulatory pathways; mainly, downstream of TGF-β signaling activity which is evident in many developmental and pathological situations in which EMT is reported, including embryogenesis, inflammation and tumor metastasis. The hallmark of TGFβ signaling is up-regulation of Snail, an E-cadherin repressor. Overexpression of Snail has been found in various fibrotic diseases, including liver fibrosis and renal fibrosis.
E-cadherin is a calcium-dependent homophilic cell adhesion molecule expressed on the cell surfaces of epithelium and is a critical structure for stratification of squamous epithelia. The significant reduction in E-cadherin expression observed in the gingival epithelium during pocket formation and is believed to contribute to the pathogenesis of periodontal disease.
Vimentin is a type III intermediate filament (IF) protein that is expressed in mesenchymal cells. IF, along with tubulin-based microtubules and actin-based microfilaments, comprises the cytoskeleton. All IF proteins are expressed in a highly developmentally-regulated fashion; vimentin is the major cytoskeletal component of mesenchymal cells. Because of this, vimentin is often used as a marker of mesenchymal-derived cells or cells undergoing EMT during both normal development and metastatic progression.
β-catenin is a dual function protein, involved in regulation and coordination of cell-cell adhesion and gene transcription. β-catenin also acts as a morphogen in later stages of embryonic development. Together with TGF-β, an important role of β-catenin is to induce a morphogenic change in epithelial cells. It induces them to abandon their tight adhesion and assume a more mobile and loosely associated mesenchymal phenotype.
Role of EMT on compromising epithelial barrier function of periodontal pocket lining is not fully elucidated yet. Reported risk factors of EMT including prolonged exposure to cytokines, Gram-negative bacteria, tobacco and hypoxia are also relevant to periodontitis. Potential induction of EMT within periodontal pockets may disrupt epithelial barrier thus facilitating invasion of pathogenic periodontal pathogens to deeper tissues resulting in further tissue breakdown and non-resolving periodontal lesion.
- Conditions
- Periodontitis, Periodontal Diseases, Epithelial-Mesenchymal Transition, Transcription Factors, Epithelial Attachment, Gram-Negative Bacteria
- Being tested
- Modified Widman flap, Gingivectomy
- Medical subject headings
- Periodontitis, Periodontal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modified Widman flapProcedure or surgery
- Administration of anaesthesia
- First incision (reversed bevel incision), scalpel is placed at 45 degree, 2mm apical to gingival margin in coronal-apical direction until touching the bone and moved continuously around the teeth without any vertical releasing incisions
- Partial mobilization of the mucoperiosteal flap (full thickness flaps both facially and orally) within the attached gingiva to the alveolar crest
- Second incision (sulcular incision)
- Third incision (horizontal incision), also interdentally to remove the delineated tissue and all granulation tissue which is used later for analysis.
- Root surface debridement
- Flap adaptation, complete coverage interdentally and suturing.
GingivectomyProcedure or surgery
- Administration of anaesthesia
- Marking the base of the sulcus with pocket marker tweezer.
- First incision (gingivectomy incision), scalpel blade placed 1mm apical to the bleeding points and the incision should be beveled 45 degrees coronally.
- Second incision (interdental) to free the tissue which is used for analysis later.
- Debriding the area and applying periodontal pack.
| Study group | Role | What they receive |
|---|---|---|
| Periodontitis | Patients with periodontitis which is defined by interdental clinical attachment loss (CAL) ≥ 2 non-adjacent teeth, or Buccal or Oral CAL ≥ 3 mm with probing pocket depth (PPD) > 3 mm is detectable at ≥2 teeth. All patients should be indicated for periodontal surgery. Receives: Procedure: Modified Widman flap | |
| Healthy periodontium | Healthy periodontium is defined by absence of CAL, PPD ≤3 mm, bleeding on probing <10%, and no evidence of radiological bone loss. Gingival samples are collected from subjects referred for gingivectomy for esthetic reasons such as crown lengthening, gummy smile or prior to teeth extraction for orthodontic treatment. Receives: Procedure: Gingivectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical attachment loss (CAL)
CAL is a linear distance (in mm) from cemento-enamel junction to the base of the sulcus/periodontal pocket measured by using a periodontal probe, recorded at six sites per tooth namely; mesio-facial, mid-facial, disto-facial, mesio-oral, mid-oral, disto-oral.
Measured: Measured at baseline only before conducting periodontal surgery
Probing pocket depth (PPD)
PPD is the distance (in mm) from the gingival margin to the base of the sulcus/periodontal pocket measured by using a periodontal probe, recorded at six sites per tooth namely; mesio-facial, mid-facial, disto-facial, mesio-oral, mid-oral, disto-oral.
Measured: Measured at baseline only before conducting periodontal surgery
Secondary outcomes (2)
Bleeding on probing (BOP)
BOP is measured by inserting a periodontal probe to the bottom of the gingival sulcus/periodontal pocket and moved gently along the tooth (root) surface. If bleeding occurs within 30 seconds after probing, the site is given score (1), and a negative score (0) for the non-bleeding site. BOP is recorded at six sites per tooth namely; mesio-facial, mid-facial, disto-facial, mesio-oral, mid-oral, disto-oral.
Measured: Measured at baseline only before conducting periodontal surgery
Immunohistochemical expression of EMT-related markers
Immunohistochemical expressions of four EMT-related markers (E-cadherin, Snail1, vimentin, β-catenin) in gingival samples collected from patients with periodontitis and healthy periodontium are measured.
Measured: Measured at baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2022
- Study start12 Jul 2021
- Primary completion30 Aug 2022 (estimated)
- Study completion30 Aug 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PeriodontitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Baghdad
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Saif Sehaam Saliem, University of Baghdad
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05403164
- Sponsor's protocol ID
- 241621
- Status last verified
- May 2022
- First submitted
- 30 May 2022
- Last updated
- 3 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Epithelial-mesenchymal Transition in Patients With Periodontitis (An Immunohistochemistry Study)
- ClinicalTrials.gov ID
- NCT05403164
- Acronym / sponsor ID
- 241621
- Conditions
- Periodontitis, Periodontal Diseases, Epithelial-Mesenchymal Transition, Transcription Factors, Epithelial Attachment, Gram-Negative Bacteria
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University of BaghdadUniversity, hospital or other
- Study start
- 12 Jul 2021 (actual)
- Primary completion
- 30 Aug 2022 (estimated)
- Study completion
- 30 Aug 2022 (estimated)
- First posted
- 3 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Periodontitis is a chronic inflammatory disease results is destruction of the attachment apparatus of the teeth and ultimately tooth loss.
Epithelial-mesenchymal transition (EMT) is a process comprises of series of events that influence a polarized epithelial cell to undergo molecular/morphological changes leading to acquisition of mesenchymal cell phenotype. This process is responsible for suppressing epithelial-phenotype and it is known to be triggered by chronic exposure to inflammatory cytokines, Gram-negative bacteria, hypoxia, smoking, and hyperglycemia.
Both periodontitis and EMT share common risk factors/promoters; however, the role of EMT in the pathogenesis of periodontitis is not fully elucidated yet. Potential induction of EMT within periodontal pockets may disrupt epithelial barrier thus facilitating invasion of pathogenic periodontal pathogens to deeper tissues resulting in further tissue breakdown and non-resolving periodontal lesion.
Detailed description
Periodontitis is a highly prevalent inflammatory disease affecting the attachment apparatus of the teeth, leading to progressive destruction of periodontal ligament and resorption of alveolar bone which if not treated, at early stages, it will lead to tooth loss. It is characterised by presence of a wide diversity of pathogenic bacteria, specifically Gram-negative anaerobes, that possess range of virulence factors responsible for triggering intense inflammatory response. Although this response is protective in nature; however, it leads to undesirable collateral damage to the surrounding tissues that is further aggravated by the aberrant immune response of the host.
Epithelial-mesenchymal transition (EMT) is a process comprises of series of events that influence a polarized epithelial cell to undergo molecular/morphological changes leading to acquisition of mesenchymal cell phenotype. EMT is modulated by range of regulatory pathways; mainly, downstream of TGF-β signaling activity which is evident in many developmental and pathological situations in which EMT is reported, including embryogenesis, inflammation and tumor metastasis. The hallmark of TGFβ signaling is up-regulation of Snail, an E-cadherin repressor. Overexpression of Snail has been found in various fibrotic diseases, including liver fibrosis and renal fibrosis.
E-cadherin is a calcium-dependent homophilic cell adhesion molecule expressed on the cell surfaces of epithelium and is a critical structure for stratification of squamous epithelia. The significant reduction in E-cadherin expression observed in the gingival epithelium during pocket formation and is believed to contribute to the pathogenesis of periodontal disease.
Vimentin is a type III intermediate filament (IF) protein that is expressed in mesenchymal cells. IF, along with tubulin-based microtubules and actin-based microfilaments, comprises the cytoskeleton. All IF proteins are expressed in a highly developmentally-regulated fashion; vimentin is the major cytoskeletal component of mesenchymal cells. Because of this, vimentin is often used as a marker of mesenchymal-derived cells or cells undergoing EMT during both normal development and metastatic progression.
β-catenin is a dual function protein, involved in regulation and coordination of cell-cell adhesion and gene transcription. β-catenin also acts as a morphogen in later stages of embryonic development. Together with TGF-β, an important role of β-catenin is to induce a morphogenic change in epithelial cells. It induces them to abandon their tight adhesion and assume a more mobile and loosely associated mesenchymal phenotype.
Role of EMT on compromising epithelial barrier function of periodontal pocket lining is not fully elucidated yet. Reported risk factors of EMT including prolonged exposure to cytokines, Gram-negative bacteria, tobacco and hypoxia are also relevant to periodontitis. Potential induction of EMT within periodontal pockets may disrupt epithelial barrier thus facilitating invasion of pathogenic periodontal pathogens to deeper tissues resulting in further tissue breakdown and non-resolving periodontal lesion.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Periodontitis | – | Procedure: Modified Widman flapPatients with periodontitis which is defined by interdental clinical attachment loss (CAL) ≥ 2 non-adjacent teeth, or Buccal or Oral CAL ≥ 3 mm with probing pocket depth (PPD) > 3 mm is detectable at ≥2 teeth. All patients should be indicated for periodontal surgery. |
| Healthy periodontium | – | Procedure: GingivectomyHealthy periodontium is defined by absence of CAL, PPD ≤3 mm, bleeding on probing <10%, and no evidence of radiological bone loss. Gingival samples are collected from subjects referred for gingivectomy for esthetic reasons such as crown lengthening, gummy smile or prior to teeth extraction for orthodontic treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Participants involved in this study are recruited from the patient attending to the Department of Periodontics, College of Dentistry, University of Baghdad. Those patients were treated non-surgically by the residents in the department. Primary endpoint of is assessed three months after completion of non-surgical therapy. Patients with persistent pockets at posterior teeth indicated for modified Widman flap are included in the study. Prior to enrollment, aims and details of the study are clearly explained to the patients who then asked to sign the consent form. All procedures in this study followed Helsinki declaration and its later amendments for conducting human researches.
Key inclusion criteria (8 listed)
- Diagnosed with generalized periodontitis, unstable, no risk factor
- Selected site should be indicated for surgical treatment by modified Widman flap in posterior area and these sites must exhibit periodontal pockets ≥ 5mm or pockets ≥ 4mm with BOP
- Plaque index score < 10%
- Never smoker or former smoker
- Not currently using systemic or local antimicrobials (at least in the last three months)
Key exclusion criteria (6 listed)
- Have history of systemic disease e.g., diabetes mellitus
- Periodontal treatment in the last 6 months
- Current participation in other clinical trials
- Pregnant women
- Current smoker
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Modified Widman flap1. Administration of anaesthesia 2. First incision (reversed bevel incision), scalpel is placed at 45 degree, 2mm apical to gingival margin in coronal-apical direction until touching the bone and moved continuously around the teeth without any vertical releasing incisions 3. Partial mobilization of the mucoperiosteal flap (full thickness flaps both facially and orally) within the attached gingiva to the alveolar crest 4. Second incision (sulcular incision) 5. Third incision (horizontal incision), also interdentally to remove the delineated tissue and all granulation tissue which is used later for analysis. 6. Root surface debridement 7. Flap adaptation, complete coverage interdentally and suturing. | Procedure or surgery | Periodontitis |
| Gingivectomy1. Administration of anaesthesia 2. Marking the base of the sulcus with pocket marker tweezer. 3. First incision (gingivectomy incision), scalpel blade placed 1mm apical to the bleeding points and the incision should be beveled 45 degrees coronally. 4. Second incision (interdental) to free the tissue which is used for analysis later. 5. Debriding the area and applying periodontal pack. | Procedure or surgery | Healthy periodontium |
Primary outcome
Clinical attachment loss (CAL)
Time frame: Measured at baseline only before conducting periodontal surgery
CAL is a linear distance (in mm) from cemento-enamel junction to the base of the sulcus/periodontal pocket measured by using a periodontal probe, recorded at six sites per tooth namely; mesio-facial, mid-facial, disto-facial, mesio-oral, mid-oral, disto-oral.
Probing pocket depth (PPD)
Time frame: Measured at baseline only before conducting periodontal surgery
PPD is the distance (in mm) from the gingival margin to the base of the sulcus/periodontal pocket measured by using a periodontal probe, recorded at six sites per tooth namely; mesio-facial, mid-facial, disto-facial, mesio-oral, mid-oral, disto-oral.
2 secondary outcomes
Bleeding on probing (BOP)
Time frame: Measured at baseline only before conducting periodontal surgery
Immunohistochemical expression of EMT-related markers
Time frame: Measured at baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Periodontitis and Periodontal Diseases, run by University of Baghdad at 1 site in Iraq.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Iraq. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Saif S Saliem, MSc (+964 7901529484, drsaifjuma@codental.uobaghdad.edu.iq), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical attachment loss (CAL) (time frame: Measured at baseline only before conducting periodontal surgery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2022.