Clinical trial NCT02172716: Disruption of Immune Homeostasis in Type 2 Diabetics With Generalized Chronic Periodontitis
Official title: Disruption of Immune Homeostasis in Type 2 Diabetics With Generalized Chronic Periodontitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Type 2 Diabetes Mellitus
Periodontal Diseases
Periodontitis
Chronic Periodontitis
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Augusta University
First posted: 2014-06-24
Enrollment: 80
Sex: ALL
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in cellular measures
timeFrame: 24 hours, 30 days and 3 months after treatment.
measure: Change from baseline in molecular measures
timeFrame: 24 hours, 30 days and 3 months after treatment.
measure: Change from baseline in the expression on mDCs
timeFrame: 24 hours, 30 days and 3 months after treatment.
Secondary outcomes:
measure: periodontal probing depth, periodontal attachment level, bleeding on probing, visible plaque and gingival bleeding.
timeFrame: Baseline, 30 days and 3 months
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: University of Sao Paulo
state: SP
Study officials:
affiliation: Professor and chair
name: Giuseppe Romito, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Post graduate student
name: Mariana Rabelo, MSc
role: STUDY_CHAIR
References: