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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Zentrum fuer Zahn-, Mund- und Kieferheilkunde
Sponsor:
Information provided by (Responsible Party):
Dr. Jens Martin Herrmann, Zentrum fuer Zahn-, Mund- und Kieferheilkunde
ClinicalTrials.gov Identifier:
NCT01848379
First received: April 29, 2013
Last updated: May 13, 2013
Last verified: May 2013

April 29, 2013
May 13, 2013
January 2012
December 2013   (final data collection date for primary outcome measure)
Change from Baseline in Clinical Attachment Level (CAL) at 6 and 12 Months [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
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.
Change from Baseline in Clinical Attachment Level (CAL) at 6 and 12 Month [ Time Frame: 0; 24; 52 weeks ] [ Designated as safety issue: No ]
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. The measurement recorded is the distance from the CEJ to the gingival margin (GM), resulting in a positive or negative value depending on whether the GM is coronal (+) or apical (-) to the CEJ.
Complete list of historical versions of study NCT01848379 on ClinicalTrials.gov Archive Site
  • Probing Pocket Depth (PPD) [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
    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) [ Time Frame: -3 weeks; 0, 6 and 12 months ] [ Designated as safety issue: No ]
    The body mass index will be assessed as the participants' body mass divided by the square of their height
  • Glycated Hemoglobin (HbA1c) [ Time Frame: -3 weeks; 0, 6 and 12 months ] [ Designated as safety issue: No ]
    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.
  • Probing Pocket Depth (PPD) [ Time Frame: 0, 24, 52 weeks ] [ Designated as safety issue: No ]
    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) [ Time Frame: 0; 24; 52 weeks ] [ Designated as safety issue: No ]
    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) [ Time Frame: -3; 0; 2; 24; 52 weeks ] [ Designated as safety issue: No ]
    The body mass index will be assessed as the participants' body mass divided by the square of their height
  • Glycated Hemoglobin (HbA1c) [ Time Frame: -3; 0; 2; 24; 52 weeks ] [ Designated as safety issue: No ]
    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.
  • Neutrophil Cytoplasmic Calcium Concentration ([Ca2+]i) [ Time Frame: -3, 0 and 2 weeks; 6 and 12 months ] [ Designated as safety issue: No ]
    [Ca2+]i: ex vivo 2nd messenger cytoplasmic calcium concentration resembles a key parameter for chemoattractive or phagocytic PMN-receptor activation.
  • Neutrophil Cytoplasmic pH (pHi) [ Time Frame: -3, 0 and 2 weeks; 6 and 12 months ] [ Designated as safety issue: No ]
    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.
  • Release of Reactive Oxygen Species (ROS) [ Time Frame: -3, 0 and 2 weeks; 6 and 12 months ] [ Designated as safety issue: No ]
    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.
  • Release of Neutrophil Elastase (EA) [ Time Frame: -3, 0 and 2 weeks; 6 and 12 months ] [ Designated as safety issue: No ]
    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.
  • Gingival Crevicular Fluid (GCF) [ Time Frame: -3 and 0 weeks ] [ Designated as safety issue: No ]
    GCF: a quantitative and qualitative assessment of the serum like exudate in the gingival crevice will be performed.
  • Global Luminol Dependent Chemiluminescence of Stimulated Neutrophils (CLt) [ Time Frame: 0 weeks ] [ Designated as safety issue: No ]
    The detection of total ROS will be performed ex vivo with a kinetic chemiluminescence assay after receptor activation of neutrophils.
  • Extracellular Luminol Dependent Chemiluminescence of Stimulated Neutrophils (CLex) [ Time Frame: 0 weeks ] [ Designated as safety issue: No ]
    The detection of extracellular ROS will be performed ex vivo with a kinetic chemiluminescence assay after receptor activation of neutrophils.
  • Cellular Immune responses [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
    Analyses of leukocyte subsets, i.e. T-lymphocytes from the peripheral venous blood samples
  • Neutrophil Cytoplasmic Calcium Concentration ([Ca2+]i) [ Time Frame: -3; 0; 2; 24; 52 weeks ] [ Designated as safety issue: No ]
    [Ca2+]i: ex vivo 2nd messenger cytoplasmic calcium concentration resembles a key parameter for chemoattractive or phagocytic PMN-receptor activation.
  • Neutrophil Cytoplasmic pH (pHi) [ Time Frame: -3; 0; 2; 24; 52 ] [ Designated as safety issue: No ]
    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.
  • Release of Reactive Oxygen Species (ROS) [ Time Frame: -3; 0; 2; 24; 52 ] [ Designated as safety issue: No ]
    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.
  • Release of Neutrophil Elastase (EA) [ Time Frame: -3; 0; 2; 24; 52 ] [ Designated as safety issue: No ]
    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.
  • Gingival Crevicular Fluid (GCF) [ Time Frame: -3 and 0 weeks ] [ Designated as safety issue: No ]
    GCF: a quantitative and qualitative assessment of the serum like exudate in the gingival crevice will be performed.
  • Global Luminol Dependent Chemiluminescence of Stimulated Neutrophils (CLt) [ Time Frame: 0 weeks ] [ Designated as safety issue: No ]
    The detection of total ROS will be performed ex vivo with an kinetic chemiluminescence assay after receptor activation of neutrophils.
  • Extracellular Luminol Dependent Chemiluminescence of Stimulated Neutrophils (CLex) [ Time Frame: 0 weeks ] [ Designated as safety issue: No ]
    The detection of extracellular ROS will be performed ex vivo with an kinetic chemiluminescence assay after receptor activation of neutrophils.
  • Cellular Immune responses [ Time Frame: 0; 24; 52 weeks ] [ Designated as safety issue: No ]
    Analyses of leukocyte subsets, i.e. T-lymphocytes from the peripheral venous blood samples
 
White Blood Cell Signaling and Defense Mechanisms in Patients With Diabetes Mellitus Type 2 and Periodontitis
Human Polymorphonuclear Neutrophil (PMN) Cytosolic Signaling and Effector Functions in Patients With Diabetes Mellitus Type 2 and Periodontitis

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.

Specific Aims

  1. 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
  2. To determine the biochemical basis for diabetic PMN alteration of motility as well as bactericidal functions: production of superoxide and release of elastase, respectively
  3. 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
  4. 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
  5. To evaluate, if systemic and periodontal intervention can lead to clinical attachment gain in patients with diabetes mellitus type 2
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Basic Science
  • Chronic Periodontitis
  • Diabetes Mellitus, Type 2
  • Procedure: ADT+FD
    Other Name: Anti-diabetic Treatment and Full Mouth Decontamination
  • Procedure: FD
    Other Name: Full Mouth Decontamination
  • Experimental: Antidiabetic Therapy(ADT)+Full Mouth Decontamination(FD)

    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)

    Intervention: Procedure: ADT+FD
  • Active Comparator: Full Mouth Deconatamination(FD)

    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)

    Intervention: Procedure: FD
  • No Intervention: No Treatment
    Healthy individuals to be monitored cross-sectional
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
45
December 2013
December 2013   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
Yes
Contact: V. Petsch, DH +49 641 9946192 vanessa.petsch@dentist.med.uni-giessen.de
Contact: J. M. Herrmann, Dr. +49 641 9946192 j.m.herrmann@dentist.med.uni-giessen.de
Germany
 
NCT01848379
DMS017507GI
Yes
Dr. Jens Martin Herrmann, Zentrum fuer Zahn-, Mund- und Kieferheilkunde
Zentrum fuer Zahn-, Mund- und Kieferheilkunde
Not Provided
Principal Investigator: Jens Martin Herrmann, Dr. Department of Periodontology, ZentrumZMK
Zentrum fuer Zahn-, Mund- und Kieferheilkunde
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP