Oral Bacteria and Immune System Problems Involved in Gum Disease (Periodontitis)

Sponsor

National Institute of Dental and Craniofacial Research (NIDCR) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT01568697

Collaborator

(none)

700

Enrollment

Location

Study Details

Study Description

Brief Summary

Background:

Gum disease is a condition in which the tissue around the tooth root becomes swollen and infected. This condition can cause tooth loss if it is not treated. Who gets gum disease and how bad it will be depends on (1) the different bacteria in the mouth and (2) how the immune system of an individual handles these bacteria. Researchers want to look at the oral bacteria and genetic immune problems of different people to learn how these affect gum disease and other conditions of the mouth.

Objectives:

To study how immune system problems may lead to problems in the mouth, including gum disease.

Eligibility:

Children and adults at least 7 years of age who have genetic problems with their immune system.
Healthy adults that have periodontal disease
Health adults that do not have periodontal disease

Design:

This study will involve a screening visit and a study visit.
Participants will be screened with a medical history, blood work and a full oral and dental exam, including dental x-rays and photos.
The study visit will involve collection of blood, urine, and other samples, including saliva, plaque, and gum swabs. Any abnormal tissue will sampled for a biopsy. Additional oral and dental exams will be performed. Participants will also answer questions about any current medical or dental problems.

Condition or Disease	Intervention/Treatment	Phase
Immunosuppression Periodontal Disease Healthy Subjects Healthy Volunteer

Detailed Description

This is a cross sectional/natural history protocol designed to investigate the clinical,

microbiologic, and immunologic consequences of genetic immune defects in the oral cavity. The hypothesis is that genetic immune defects will lead to alterations in the local immune response and microbial colonization and ultimately predispose to susceptibility to oral infections and inflammatory conditions.

In the cross-sectional phase the following individuals will be enrolled, evaluated and screened for presence and severity of periodontitis, presence of a genetic defects and sampled for studies in oral immunity and microbiome: 1) individuals diagnosed with genetic immune defects 2) individuals with severe periodontitis of suspected genetic etiology and their family members 3) healthy volunteers. Subjects identified with a genetic immune defect and with presence of oral disease (primarily periodontitis) may enter the natural history phase of the study to be clinically followed at the National Institutes of Health (NIH) over time. This protocol aims to determine whether specific genetic immune defects will predispose to oral disease (primarily periodontitis) and to better understand consequences of immune deficiency on the oral immune response and microbiome.

Primary Objectives

Investigate the degree, scope, etiology and natural history of oral manifestations in patients with genetic immune defects.
Characterize the immune response in the oral cavity of patients with genetic immune defects.
Characterize the microbiome in the oral cavity of patients with genetic immune defects.

Secondary Objectives

Assay development/validation for the study of tissue immunity and microbiome characterization
Establishment of normative values for immune mediators and microbial elements at the oral cavity

Study Population (s)

The study population will include:

Subjects with genetic immune defects
Subjects with severe periodontitis of suspected genetic etiology and their family members
Healthy volunteers (with/without periodontal disease)

Design

This is a cross-sectional/natural history study for the evaluation of clinical, immunologic, and microbiologic oral manifestations (primarily periodontitis) in patients diagnosed with genetic immune defects or those with severe periodontitis of suspected genetic etiology and healthy volunteer subjects.

Cross Sectional Phase: Three groups of subjects will be enrolled in the cross-sectional phase of the study 1) individuals diagnosed with genetic immune defects 2) individuals with severe periodontitis of suspected genetic etiology and their family members that include parents or siblings 3) healthy volunteers (with/without periodontal disease). All groups will be evaluated for oral disease (periodontitis) and sampled for oral immunity, systemic immunity and microbiome characterization. Individuals with severe periodontitis in the presence/absence of a genetic defect may be offered the option of receiving standard of care inflammatory control periodontal treatment at NIH without travel compensation, following the cross-sectional portion of the study. Family members (parents or siblings) of individuals with periodontal disease of suspected genetic may be asked to participate in this study. During the course of genetic testing, family members may be enrolled in the cross sectional phase of the study for phenotyping and genetic testing.

Natural History Phase: Subjects identified with a genetic defect with the presence of oral disease may enroll in the natural history phase of the study to be followed clinically over time.

Primary Outcome Measures

Clinical intraoral characterization (i.e., presence and severity of periodontitis).
Characterize the immune response in the oral cavity of patients with genetic immune defects
Characterize the microbiome in the oral cavity of patients with genetic immune defects

Secondary Outcome Measures

Assay development/validation for the study of tissue immunity and microbiome characterization
Establishment of normative values for immune mediators and microbial elements at the oral cavity

Exploratory Outcome Measures

Initial data from this study may generate new hypotheses for investigation as part of this study.

Study Design

Study Type:

Observational

Anticipated Enrollment :

700 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

Oral Microbial and Immunological Characterization of Patients With Immune Dysfunction

Actual Study Start Date :

Oct 5, 2012

Arms and Interventions

Arm	Intervention/Treatment
Healthy Volunteers Healthy volunteers (with/without periodontal disease)
Immune deficient patients Subjects with known genetic immune deficiency
Subjects with severe periodontitis of suspected genetic etiology and their family Subjects with severe periodontitis of suspected genetic etiology and their family members

Outcome Measures

Primary Outcome Measures

Clinical intraoral characterization (i.e., presence and severity of periodontitis). [15 years]
The primary clinical endpoints of the study are severity and types of oral disease: specifically for periodontal disease, mean PD, mean CAL, proportion of sites with PD >5 mm, and proportion of subjects with BOP, proportion of patient with other inflammatory conditions or infections of the oral cavity by immune disorder. Characterization of the oral microbiome in patients with monogenic immune defects. Immunologic endpoints: types and levels of immune mediators in the saliva, GCF, oral tissues, and/or blood.
Characterize the immune response in the oral cavity of patients with genetic immune defects [15 years]
The primary clinical endpoints of the study are severity and types of oral disease: specifically for periodontal disease, mean PD, mean CAL, proportion of sites with PD >5 mm, and proportion of subjects with BOP, proportion of patient with other inflammatory conditions or infections of the oral cavity by immune disorder. Characterization of the oral microbiome in patients with monogenic immune defects. Immunologic endpoints: types and levels of immune mediators in the saliva, GCF, oral tissues, and/or blood.
Characterize the microbiome in the oral cavity of patients with genetic immune defects [15 years]
The primary clinical endpoints of the study are severity and types of oral disease: specifically for periodontal disease, mean PD, mean CAL, proportion of sites with PD >5 mm, and proportion of subjects with BOP, proportion of patient with other inflammatory conditions or infections of the oral cavity by immune disorder. Characterization of the oral microbiome in patients with monogenic immune defects. Immunologic endpoints: types and levels of immune mediators in the saliva, GCF, oral tissues, and/or blood.

Secondary Outcome Measures

1. Assay development/validation for the study of tissue immunity and microbiome characterization 2. Establishment of normative values for immune mediators and microbial elements at the oral cavity [15 years]
Validate methodologies for measuring levels of immune mediators in oral fluids - Establish normative values of immune mediators in oral fluids and tissues - Assay development; Develop new methodologies to study pathways of the immune response in the oral cavity - Assay development: Develop new methodologies to study the microbiome in the oral cavity

Eligibility Criteria

Criteria

Ages Eligible for Study:

7 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

INCLUSION CRITERIA:

Patients with Genetic Immune Defects:

-Patients with an established monogenic immune defect will be eligible for screening inclusion under this protocol.

Diagnosis of monogenic immune defect
Greater than or equal to 7 years old

Severe Periodontitis of Suspected Genetic Etiology and Family Members:

History of severe periodontitis prior to age <30
Willing to allow genetic testing
Greater than or equal to 7 years old
In good general health

Healthy Volunteer Subjects:

In good general health
Greater than or equal to 18 years old
Willing to allow genetic testing
Have a minimum of 20 natural teeth

Inclusion Criteria for Natural History phase, all subjects:

Diagnosis of genetic immune defect
Presence of oral manifestation (primarily periodontitis)

Inclusion Criteria for standard of care treatment:

Active untreated disease (visible signs of tissue inflammation including erythema/edema, generalized bleeding upon probing)
Periodontal disease defined as bone loss of >5mm as measured on

periodontal exam.

EXCLUSION CRITERIA:

All Subjects:

History of Hepatitis B or C
History of HIV
Prior radiation therapy to the head or neck
Have an active malignancy except localized basal or squamous cell carcinoma of the skin
Have been treated with systemic chemotherapeutics or radiation therapy within 5 years of screening
Pregnant or lactating
If participation in the protocol would not be safe or in the subject s best interest in the opinion of either the PI or the primary medical team.

Additional Exclusions for Healthy Volunteers:

Diagnosis of diabetes and/or HbA1C level >6%
More than 3 hospitalizations in the last 3years
Have an autoimmune disorder such as Lupus, Rheumatoid arthritis, etc.
In the 3 months before study enrollment, have used any of the following:
Systemic (intravenous, intramuscular, or oral) antibiotics
Oral, intravenous, intramuscular, intranasal, or inhaled corticosteroids or other immunosuppressants (e.g., cyclosporine)
Cytokine therapy
Methotrexate or immunosuppressive chemotherapeutic agents
Large doses of commercial probiotics (greater than or equal to 10(8) colony-forming units or organisms per day); includes tablets, capsules, lozenges, chewing gum, or powders in which a probiotic is a primary component; ordinary dietary components such as fermented beverages/milks, yogurts, and foods do not apply
Have used tobacco products (including e-cigarettes) within 1 year of screening
Unwillingness to consent to oral biopsy
NIH employees working in the Oral Immunity and Inflammation Unit and members of the Clinical Research Core Team will not be eligible for enrollment.

Additional Exclusions for Healthy Volunteers with Periodontal Disease:

Mild/moderate non-active disease (absence of active inflammatory lesions)
Subjects with urgent/complex restorative needs (ex. severe active carious lesions/fractured dentition)
Subjects in need for advance periodontal care (including bone/tissue grafts/implants)