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White Blood Cell Signaling and Defense Mechanisms in Patients With Diabetes Mellitus Type 2 and Periodontitis (DMS)

Primary Purpose

Chronic Periodontitis, Diabetes Mellitus, Type 2

Status
Unknown status
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
ADT+FD
FD
Sponsored by
Zentrum fuer Zahn-, Mund- und Kieferheilkunde
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Chronic Periodontitis

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Diabetes Mellitus, Type II
  • Glycated Hemoglobin ≥8.5%
  • Chronic Periodontitis
  • Patients and controls should have at least 12 natural teeth (without subgingival fillings, crowns or caries)

Exclusion Criteria:

  • Pregnancy
  • Smoking
  • Low Body Mass Index (BMI <18.5kg/m*m)
  • Severe cardiovascular disease including coronary artery disease, cerebral vascular disease, peripheral vascular disease, valvular heart disease, and congestive heart failure
  • Other major illnesses including cancer, liver disease, pulmonary disease, chronic infectious disease other than periodontitis (HIV, hepatitis, etc.), rheumatological disease, hematological disease, or any condition requiring hospitalization or chronic medical therapy other than diabetes.
  • Major psychiatric illness requiring treatment, or that might interfere with the ability to understand or cooperate with the protocol
  • Ongoing alcohol or drug abuse; all forms of medication or illegal substance abuse
  • Systemic enteral or parenteral medication, in part daily vitamin or anti-oxidative supplementation and certain calcium channel blockers (i.e. Nifedipine); but anti diabetic drugs or insulin substitution
  • Allergies to antibiotics or adjuvant medication / antiseptics as well as dental materials in use (including gloves) in particular those against topical antiseptic solutions i.e. chlorhexidine / N',N'''''-hexane-1,6-diylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)] or povidone iodine / 2-Pyrrolidinone, 1-ethenyl-, homopolymer, compound with iodine
  • Severe dental disease defined as severe dental caries, and/or severe pulpal disease requiring surgical correction, or any other mucosal or dental condition not readily treated, or requiring extensive dental, oral surgical or prosthetic treatment, or any other oral treatment which could affect the outcome of periodontal therapy or diseases or syndromes that require systemic medication.
  • Systemic, topical or inhaled steroid treatment for more than 30 consecutive days within 6 weeks of baseline.
  • Any periodontal treatment within 6 months prior to baseline
  • For controls: a periodontal screening index (PSI) > 1

Sites / Locations

  • Department of Periodontontology, ZentrumZMK

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

No Intervention

Arm Label

Antidiabetic Therapy(ADT)+Full Mouth Decontamination(FD)

Full Mouth Deconatamination(FD)

No Treatment

Arm Description

ADT: (Par-)enteral, anti-diabetic medication, diet and dietetic supervision, physiotherapy and physical exercises FD: The oral use of topical antiseptics prior and after mechanical tooth debridement, tooth as well as root surface planing and soft tissue decontamination in combination with systemic antibiotics (a combination of amoxicillin and metronidazole - if no microbial resistances were detected)

FD: The oral use of topical antiseptics prior and after mechanical tooth debridement, tooth as well as root surface planing and soft tissue decontamination in combination with systemic antibiotics (a combination of amoxicillin and metronidazole - if no microbial resistances were detected)

Healthy individuals to be monitored cross-sectional

Outcomes

Primary Outcome Measures

Change from Baseline in Clinical Attachment Level (CAL) at 6 and 12 Months
CAL: Clinically and quantitatively, level of attachment is defined as the distance in mm from the cemento-enamel junction (CEJ) of the teeth to the bases of the periodontal pockets. Attachment gain may be found during healing or periodontal treatment procedures.

Secondary Outcome Measures

Probing Pocket Depth (PPD)
PPD: also called periodontal probing depth is defined as the distance in millimeters from the gingival margin to the base of the sulcus or periodontal pocket. It is measured on six surfaces/tooth (disto-buccal, mid-buccal, mesio-buccal, disto-lingual, mid-lingual, and mesio-lingual) of all teeth present using the pressure calibrated Florida probe.
Bleeding on Probing (BOP)
BOP: will be determined by recording the presence or absence of bleeding following probing to determine pocket depth (PPD). This parameter will be expressed as % bleeding sites out of all examined sites in the dentition and will be documented with the Florida probe software.
Body Mass Index (BMI)
The body mass index will be assessed as the participants' body mass divided by the square of their height
Glycated Hemoglobin (HbA1c)
Physiological levels of blood glucose result in a normal amount of glycated hemoglobin. Treatment procedures may help to reduce plasma glucose in individuals with diabetes mellitus type 2, thus, in a timely extended fashion the fraction of glycated hemoglobin.

Full Information

First Posted
April 29, 2013
Last Updated
June 30, 2017
Sponsor
Zentrum fuer Zahn-, Mund- und Kieferheilkunde
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1. Study Identification

Unique Protocol Identification Number
NCT01848379
Brief Title
White Blood Cell Signaling and Defense Mechanisms in Patients With Diabetes Mellitus Type 2 and Periodontitis
Acronym
DMS
Official Title
Human Polymorphonuclear Neutrophil (PMN) Cytosolic Signaling and Effector Functions in Patients With Diabetes Mellitus Type 2 and Periodontitis
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Unknown status
Study Start Date
January 2012 (undefined)
Primary Completion Date
December 2017 (Anticipated)
Study Completion Date
December 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zentrum fuer Zahn-, Mund- und Kieferheilkunde

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
White blood cell membrane and surface structures are affected by the metabolic disorders and complications found in diabetes mellitus. Therefore, cellular activation, signal propagation, intracellular signaling as well as bactericidal effector functions are altered. When diabetic symptoms are corrected by the systemic intervention and treatment of the patients (Anti-diabetic Therapy/ADT, i.e. anti-diabetic medication, diet and dietetic supervision, physiotherapy and physical exercises), white blood cell functions will then normalize and reach the functionality comparable to those cells derived from healthy subjects. Gum diseases like periodontitis have long been associated with and termed complications of uncontrolled diabetes mellitus. Vice versa, after diabetic conditions are corrected, periodontitis treatment will be proven effective, when oral hygiene regimen, full mouth decontamination (FD, i.e. the oral use of topical antiseptics prior and after professional mechanical tooth cleaning, tooth as well as root surface planing, polishing as well as gum and soft tissue decontamination in combination with systemic antibiotics) are performed. To reinforce gum healing, reinfection prevention (RP) as well as supportive periodontal therapy (SPT) will be administered by dental professionals on an individual basis and a detailed schedule. If periodontal pockets critical for participant's self care are not eliminated by FD including RP and SPT, and niches >5mm after 6 month persist, patients are informed and offered surgical intervention as indicated for gum disease elimination. Dental follow up exams will be offered to all participants.
Detailed Description
Specific Aims To investigate if cytosolic Ca2+- ( delta[Ca2+]i) and pH (delta_pHi) signaling responses and bactericidal effector functions of PMN dependent upon the status of diabetic control and are reduced or increased when compared to age and gender matched controls To determine the biochemical basis for diabetic PMN alteration of motility as well as bactericidal functions: production of superoxide and release of elastase, respectively To characterize the molecular basis of the observed alterations in the regulation of cytosolic calcium (delta[Ca2+]i) and pH (delta_pHi) exhibited by diabetic PMN To investigate if the pre-activated state and altered bactericidal functionality of diabetic PMN are reversed when the patients' glycemic control is normalized, blood glucose levels as well as periodontal disease are corrected To evaluate, if systemic and periodontal intervention can lead to clinical attachment gain in patients with diabetes mellitus type 2

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Periodontitis, Diabetes Mellitus, Type 2

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Antidiabetic Therapy(ADT)+Full Mouth Decontamination(FD)
Arm Type
Experimental
Arm Description
ADT: (Par-)enteral, anti-diabetic medication, diet and dietetic supervision, physiotherapy and physical exercises FD: The oral use of topical antiseptics prior and after mechanical tooth debridement, tooth as well as root surface planing and soft tissue decontamination in combination with systemic antibiotics (a combination of amoxicillin and metronidazole - if no microbial resistances were detected)
Arm Title
Full Mouth Deconatamination(FD)
Arm Type
Active Comparator
Arm Description
FD: The oral use of topical antiseptics prior and after mechanical tooth debridement, tooth as well as root surface planing and soft tissue decontamination in combination with systemic antibiotics (a combination of amoxicillin and metronidazole - if no microbial resistances were detected)
Arm Title
No Treatment
Arm Type
No Intervention
Arm Description
Healthy individuals to be monitored cross-sectional
Intervention Type
Procedure
Intervention Name(s)
ADT+FD
Other Intervention Name(s)
Anti-diabetic Treatment and Full Mouth Decontamination
Intervention Type
Procedure
Intervention Name(s)
FD
Other Intervention Name(s)
Full Mouth Decontamination
Primary Outcome Measure Information:
Title
Change from Baseline in Clinical Attachment Level (CAL) at 6 and 12 Months
Description
CAL: Clinically and quantitatively, level of attachment is defined as the distance in mm from the cemento-enamel junction (CEJ) of the teeth to the bases of the periodontal pockets. Attachment gain may be found during healing or periodontal treatment procedures.
Time Frame
0, 6 and 12 months
Secondary Outcome Measure Information:
Title
Probing Pocket Depth (PPD)
Description
PPD: also called periodontal probing depth is defined as the distance in millimeters from the gingival margin to the base of the sulcus or periodontal pocket. It is measured on six surfaces/tooth (disto-buccal, mid-buccal, mesio-buccal, disto-lingual, mid-lingual, and mesio-lingual) of all teeth present using the pressure calibrated Florida probe.
Time Frame
0, 6 and 12 months
Title
Bleeding on Probing (BOP)
Description
BOP: will be determined by recording the presence or absence of bleeding following probing to determine pocket depth (PPD). This parameter will be expressed as % bleeding sites out of all examined sites in the dentition and will be documented with the Florida probe software.
Time Frame
0, 6 and 12 months
Title
Body Mass Index (BMI)
Description
The body mass index will be assessed as the participants' body mass divided by the square of their height
Time Frame
-3 weeks; 0, 6 and 12 months
Title
Glycated Hemoglobin (HbA1c)
Description
Physiological levels of blood glucose result in a normal amount of glycated hemoglobin. Treatment procedures may help to reduce plasma glucose in individuals with diabetes mellitus type 2, thus, in a timely extended fashion the fraction of glycated hemoglobin.
Time Frame
-3 weeks; 0, 6 and 12 months
Other Pre-specified Outcome Measures:
Title
Neutrophil Cytoplasmic Calcium Concentration ([Ca2+]i)
Description
[Ca2+]i: ex vivo 2nd messenger cytoplasmic calcium concentration resembles a key parameter for chemoattractive or phagocytic PMN-receptor activation.
Time Frame
-3, 0 and 2 weeks; 6 and 12 months
Title
Neutrophil Cytoplasmic pH (pHi)
Description
pHi: ex vivo liganded neutrophil receptors initiate a series of signals, resulting in phagocytosis of an entity and release of the phagocyte granules' contents as well as oxidative products. The specific mechanisms by which these effector functions occur depend upon the receptor involved among [Ca2+]i is changes of pHi.
Time Frame
-3, 0 and 2 weeks; 6 and 12 months
Title
Release of Reactive Oxygen Species (ROS)
Description
ROS: these NADPH products are predominantly found within phagolysosomal compartments of the neutrophils. During phagocytosis, neutrophils may release ROS resulting in collateral tissue damage. The reactivity of ROS release will be assessed ex vivo after activation of chemoattractant as well as phagocytic receptors of the cells.
Time Frame
-3, 0 and 2 weeks; 6 and 12 months
Title
Release of Neutrophil Elastase (EA)
Description
EA: residing in the azurophilic granules of the neutrophils, elastase is activated after phagolysosomal fusion; thence, in proximity to the engulfed entities it unfolds bactericidal activity by degrading valine-rich proteins. The elastolytic activity will be assessed ex vivo after chemoattractant as well as phagocytic activation of the neutrophils' receptors.
Time Frame
-3, 0 and 2 weeks; 6 and 12 months
Title
Gingival Crevicular Fluid (GCF)
Description
GCF: a quantitative and qualitative assessment of the serum like exudate in the gingival crevice will be performed.
Time Frame
-3 and 0 weeks
Title
Global Luminol Dependent Chemiluminescence of Stimulated Neutrophils (CLt)
Description
The detection of total ROS will be performed ex vivo with a kinetic chemiluminescence assay after receptor activation of neutrophils.
Time Frame
0 weeks
Title
Extracellular Luminol Dependent Chemiluminescence of Stimulated Neutrophils (CLex)
Description
The detection of extracellular ROS will be performed ex vivo with a kinetic chemiluminescence assay after receptor activation of neutrophils.
Time Frame
0 weeks
Title
Cellular Immune responses
Description
Analyses of leukocyte subsets, i.e. T-lymphocytes from the peripheral venous blood samples
Time Frame
0, 6 and 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Diabetes Mellitus, Type II Glycated Hemoglobin ≥8.5% Chronic Periodontitis Patients and controls should have at least 12 natural teeth (without subgingival fillings, crowns or caries) Exclusion Criteria: Pregnancy Smoking Low Body Mass Index (BMI <18.5kg/m*m) Severe cardiovascular disease including coronary artery disease, cerebral vascular disease, peripheral vascular disease, valvular heart disease, and congestive heart failure Other major illnesses including cancer, liver disease, pulmonary disease, chronic infectious disease other than periodontitis (HIV, hepatitis, etc.), rheumatological disease, hematological disease, or any condition requiring hospitalization or chronic medical therapy other than diabetes. Major psychiatric illness requiring treatment, or that might interfere with the ability to understand or cooperate with the protocol Ongoing alcohol or drug abuse; all forms of medication or illegal substance abuse Systemic enteral or parenteral medication, in part daily vitamin or anti-oxidative supplementation and certain calcium channel blockers (i.e. Nifedipine); but anti diabetic drugs or insulin substitution Allergies to antibiotics or adjuvant medication / antiseptics as well as dental materials in use (including gloves) in particular those against topical antiseptic solutions i.e. chlorhexidine / N',N'''''-hexane-1,6-diylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)] or povidone iodine / 2-Pyrrolidinone, 1-ethenyl-, homopolymer, compound with iodine Severe dental disease defined as severe dental caries, and/or severe pulpal disease requiring surgical correction, or any other mucosal or dental condition not readily treated, or requiring extensive dental, oral surgical or prosthetic treatment, or any other oral treatment which could affect the outcome of periodontal therapy or diseases or syndromes that require systemic medication. Systemic, topical or inhaled steroid treatment for more than 30 consecutive days within 6 weeks of baseline. Any periodontal treatment within 6 months prior to baseline For controls: a periodontal screening index (PSI) > 1
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jens Martin Herrmann, Dr.
Organizational Affiliation
Department of Periodontology, ZentrumZMK
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Periodontontology, ZentrumZMK
City
Giessen
ZIP/Postal Code
35392
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
31912903
Citation
Herrmann JM, Sonnenschein SK, Groeger SE, Ewald N, Arneth B, Meyle J. Refractory neutrophil activation in type 2 diabetics with chronic periodontitis. J Periodontal Res. 2020 Apr;55(2):315-323. doi: 10.1111/jre.12717. Epub 2020 Jan 8.
Results Reference
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White Blood Cell Signaling and Defense Mechanisms in Patients With Diabetes Mellitus Type 2 and Periodontitis

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