Disruption of Immune Homeostasis in Type 2 Diabetics With Generalized Chronic Periodontitis

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Disruption of Immune Homeostasis in Type 2 Diabetics With Generalized Chronic Periodontitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02172716
• Other study ID #: 26793214.9.0000.0075
• Status: Completed
• Phase: N/A
• Start date: May 2014
• Est. completion date: May 2016

Study information

• Verified date: May 2018
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to assess the short-term immune response of type-2 diabetics with generalized chronic periodontitis (GCP) to nonsurgical periodontal treatment.

The investigators hypothesize that type-2 diabetes exacerbates the disruption of DC (dendritic cells)-mediated immune homeostasis associated with periodontitis.

Description:

Objectives: The primary objective of this study is to assess the short-term immune response of type-2 diabetics with generalized chronic periodontitis (GCP) to nonsurgical periodontal treatment.

Hypothesis: we hypothesize that type-2 diabetes exacerbates the disruption of DC-mediated immune homeostasis associated with periodontitis.

Subject population: Four groups comprising 80 subjects will be selected to participate: type 2 diabetics with GCP (n=20), prediabetics with GCP (n=20), normoglycemics with GCP (n=20) and healthy controls (n=20).

Study design: discovery study nested within a single-arm, single blinded clinical trial.

Experimental periods: Screening/Baseline Visit, Treatment Visit, 24 hours, 30 days and 3 months after treatment.

Intervention: Nonsurgical periodontal treatment will be conducted following a full-mouth approach; no antibiotics or chemical plaque control will be provided.

Primary outcomes:

• Cellular measures: Blood PBMCs- counts of myeloid DC (BDCA-1+CD19-), Plasmacytoid DC (cd123+cd303+) NK (CD56+CD16+), Th17, Treg (CD25+, CD39,CD73,CD127, cd152)

• Molecular measures: (Serum/crevicular fluid/ saliva): Anti-mfa-1 IgG (ELISA), Levels of IDO-1, TGFβ, TNFα, IL-1β, IL-6, IL-2, IL-10, IL-17, IL-23, IFNγ, CXCL12 (SDF1) by Multiplexing Luminex immunoassay [MAGPIX®]), performed in triplicate

• Expression on mDCs by custom qrt-PCR array (One step-fast cycle Taqman®, life technologiesTM of: angiopoietin-2, follistatin, GM-CSF, G-CSF, HGF, IL8, IL-6, leptin, PDGF-BB, PECAM-1, VEGF, TGFβ, IDO-1, IL-10, IL-1β, caspase-1, IL-17, IL-23, IL-23R IL-33, IL-12 p70, TRAIL, FOX01, Bcl-2, CXCL12 (SDF-1), CCL19, CCL21 analyzed in triplicate.

• Secondary outcomes: periodontal probing depth, periodontal attachment level, bleeding on probing, visible plaque and gingival bleeding.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: May 2016
• Est. primary completion date: May 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 35 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Subjects aged between 35 and 65 years

2. Subject diagnosed with T2DM (HbA1C =6.5), prediabetic (HbA1C =5.7 and =6.4) and non-diabetic (HbA1C =5.6) according to American Diabetes Association, 2013.

3. Subjects with GCP (PPD =5 mm in =10 teeth and BOP in =30% of sites) and without GCP (PPD =4mm and BOP in <30% sites)

4. Non-smokers or former smokers =5 years after quitting

Exclusion Criteria:

1. Pregnant or lactating women

2. Subjects taking medications known to affect the periodontium including phenytoin, cyclosporine

3. Subjects with immunosuppressive conditions or diseases including HIV infection or Hepatitis (B, C).

4. Subjects who require antibiotic prophylaxis for dental procedures.

5. Subjects who have taken antibiotics in the last 6 months

6. Subjects taking daily NSAIDS or on steroidal anti- inflammatory medications

Related Conditions & MeSH terms

• Chronic Periodontitis
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Gingival Diseases
• Periodontal Diseases
• Periodontitis
• Type 2 Diabetes Mellitus

Intervention

Procedure:
• Nonsurgical periodontal treatment
All patients with GCP will receive full-mouth scaling and root planning under local analgesia in one session. Hopeless teeth will be treated similarly and extracted after de 30 days visit. Oral hygiene instructions will be given as needed. Supragingival scaling Periodontally healthy subjects will receive supra-gingival scaling and polishing in one appointment as needed. Oral hygiene instructions will be given as needed.

Locations

Country	Name	City	State
Brazil	University of Sao Paulo	Sao Paulo	SP

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	Augusta University

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in cellular measures	Cellular measures: Blood PBMCs- counts of myeloid DC (BDCA-1+CD19-), Plasmacytoid DC (cd123+cd303+) NK (CD56+CD16+), Th17, Treg (CD25+, CD39,CD73,CD127, cd152)	24 hours, 30 days and 3 months after treatment.
Primary	Change from baseline in molecular measures	Molecular measures: (Serum/crevicular fluid/ saliva): Anti-mfa-1 IgG (ELISA), Levels of IDO-1, TGFß, TNFa, IL-1ß, IL-6, IL-2, IL-10, IL-17, IL-23, IFN?, CXCL12 (SDF1) by Multiplexing Luminex immunoassay [MAGPIX®]), performed in triplicate	24 hours, 30 days and 3 months after treatment.
Primary	Change from baseline in the expression on mDCs	Expression on mDCs by custom qrt-PCR array (One step-fast cycle Taqman®, life technologiesTM of: angiopoietin-2, follistatin, GM-CSF, G-CSF, HGF, IL8, IL-6, leptin, PDGF-BB, PECAM-1, VEGF, TGFß, IDO-1, IL-10, IL-1ß, caspase-1, IL-17, IL-23, IL-23R IL-33, IL-12 p70, TRAIL, FOX01, Bcl-2, CXCL12 (SDF-1), CCL19, CCL21 analyzed in triplicate.	24 hours, 30 days and 3 months after treatment.
Secondary	periodontal probing depth, periodontal attachment level, bleeding on probing, visible plaque and gingival bleeding.		Baseline, 30 days and 3 months