Dental Carotid Cognitive Study

July 16, 2021 updated by: Brajesh Lal, University of Maryland, Baltimore

Treatment of Periodontitis to Prevent Dementia in Older Adults With Asymptomatic Carotid Artery Stenosis and Mild Cognitive Impairment

Periodontal Disease (PD) is present in 60+% of adults >65 years and is associated with tobacco smoking, diabetes, and atherosclerosis that worsen inflammation, comorbidities common in older people with mild to moderate cognitive impairment (MCI). Older MCI patients are prone to poor oral hygiene and dental health, which if untreated worsens inflammation-mediated brain and nervous system function, and accelerates progression to dementia. Asymptomatic carotid artery stenosis (ACAS) is often a silent disease detected in only ~10% of older adults, and may have a strong association with MCI. This study examines the effects of intensive therapy for periodontitis on cognition in high-risk older people with ACAS. Results could highlight PD as a readily modifiable risk factor for dementia.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Periodontal Disease (PD) is present in 60+% of adults >65 years and is associated with tobacco smoking, diabetes, and atherosclerosis that worsen inflammation, comorbidities common in older people with mild to moderate cognitive impairment (MCI). Older MCI patients are prone to poor oral hygiene and dental health, which if untreated worsens inflammation-mediated brain and nervous system function, and accelerates progression to dementia. Asymptomatic carotid artery stenosis (ACAS) is often a silent disease detected in only ~10% of older adults, and may have a strong association with MCI. This study examines the effects of intensive therapy for periodontitis on cognition in high-risk older people with ACAS. Results could highlight PD as a readily modifiable risk factor for dementia.

This pilot study examines the hypothesis that intensive treatment of PD (IPT) in older people with MCI and ACAS will attenuate their cognitive decline by reducing oral microbial-mediated inflammation and improving cerebrovascular endothelial function that contribute to neurodegeneration-associated dementia.

The aims are to determine the effects of intensive compared to control PD treatment (randomized: IPT vs. CPT) in 60 MCI subjects with ACAS and PD on 1) Cognitive function (Primary Outcome) and quality of life (Secondary Outcome), and 2) The potential mechanisms mediating these effects

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland - Administrative Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 100 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age equal to or greater than 65 years.
  • Body Mass Index 18-35 kg/m2
  • Mild to moderate periodontitis
  • Mild to moderate cognitive impairment on Montreal Cognitive Assessment (MoCA) -range greater than or equal to 17 and less than or equal to 26 (i.e., range from 17-26).
  • Detectable carotid plaque and carotid artery stenosis <70% as diagnosed by doppler ultrasound.
  • Able to perform prescribed dental hygiene and travel to medical center as required to participate in the study.

Exclusion Criteria:

  • Inability to provide informed consent.
  • Subjects with inability to perform cognitive and other research testing
  • Prior stroke, depression (CESD >16), neurologic or psychiatric disease that would affect cognitive testing, participation, and compliance to the research study.
  • Subjects requiring chronic treatment with systemic corticosteroids or other systemic immunosuppressive drugs or drugs that would affect the dental treatments in the protocol are excluded.
  • Subjects requiring essential dental care (e.g., treatment for grossly decayed teeth, broken teeth, dental abscesses, peri-apical infections, other dental infections).
  • Inability to perform FDG-PET due to renal disease (eGFR <30 mL/min/1.75m2).
  • Receiving anticoagulant therapy (Warfarin) with an INR greater than 3.3 at time of dental treatment or with a bleeding disorder, or other diseases that may interfere with dental therapy.
  • Subjects with medical conditions that the clinicians feel would limit their ability to participate.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Standard treatment (control)
Dental evaluation and dental prophylaxis at baseline, 3, 6, and 9 months and standard oral hygiene instruction.
Procedure: Standard Treatment
Dental evaluation at baseline, 3, 6, and 9 months.
EXPERIMENTAL: Intensive Treatment
Dental evaluation at baseline, 3, 6, and 9 months. Plus one or more sessions as needed at baseline of full mouth supra- and sub-gingival scaling and root planing, plus oral hygiene instruction. Additional sessions as necessary to remove remaining local factors and treat inflammation and bacteria overgrowth. Additional evaluations and therapy at 2 months or as needed based on therapeutic response. If bleeding on probing levels do not decrease to <20% of sites following initial therapy or at subsequent visits, intermediate treatment visits will be scheduled. Each participant will be instructed to use half of a capful of 0.12% chlorhexidine twice a day during active treatment including two weeks beyond the treatment visit.
Procedure: Intensive Treatment
Dental evaluation at baseline, 3, 6, and 9 months. Plus one or more sessions as needed at baseline of full mouth supra- and sub-gingival scaling and root planing, plus oral hygiene instruction. Additional sessions as necessary to remove remaining local factors and treat inflammation and bacteria overgrowth. Additional evaluations and therapy at 2 months or as needed based on therapeutic response. If bleeding on probing levels do not decrease to <20% of sites following initial therapy or at subsequent visits, intermediate treatment visits will be scheduled. Each participant will be instructed to use half of a capful of 0.12% chlorhexidine twice a day during active treatment including two weeks beyond the treatment visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in performance on Montreal Cognitive Assessment (MoCA)
Time Frame: 1 year
The Montreal Cognitive Assessment (MoCA) is 30 item screening tool used to detect cognitive impairment. Score: 30 points (maximum), 0 points (minimum). Higher scores indicate better cognitive function. Differences in rate of change of MoCA score in those on intensive treatment for periodontitis and those receiving standard care.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of oral bacteria in saliva and dental plaque samples
Time Frame: 1 year
Dental plaque and saliva samples will be analyzed for differences in species of oral microbial biology between those on standard care compared to those on intensive treatment for periodontitis. Oral microbiome will be characterized using molecular genetic methods.
1 year
Presence of bacteria in stool samples
Time Frame: 1 year
Stool samples will be analyzed for differences in species of oral microbial biology between those on standard care compared to those on intensive treatment for periodontitis. Stool microbiome will be characterized using molecular genetic methods.
1 year
Systemic inflammation
Time Frame: 1 year
Differences in inflammatory markers such as Interleukin 6 (IL-6) and tumor necrosis factor (TNF) alpha found in blood samples in those on standard care compared to those on intensive treatment for periodontitis.
1 year
Change from baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Metabolic Measure of Standard Uptake Value Ratio (SUVR)
Time Frame: 1 year
Brain metabolic activity or glucose metabolism will be determined using the FDG-PET scan by reporting results as SUVR and compared in those on intensive treatment for periodontitis and those receiving standard treatment for periodontitis.
1 year
Changes in performance on Wechsler Adult Intelligence Scale (WAIS)-III Digit Span subtest
Time Frame: 1 year
Change in Digit Span score as a measure of working memory in those on standard care compared to those on intensive treatment for periodontitis. Raw score: 0-30, t score 19-77
1 year
Changes in performance on Hopkins Verbal Learning Test
Time Frame: 1 year
Change in Hopkins Verbal Learning test score in those on standard care compared to those on intensive treatment for periodontitis. Total raw score: 0 (minimum)-36 (maximum), t score 19-77. Higher scores indicate higher functioning.
1 year
Changes in performance on Brief Visuospatial Memory test
Time Frame: 1 year
Change in Brief Visuospatial Memory test score in those on standard care compared to those on intensive treatment for periodontitis. Total raw score : 0 (minimum)-36 (maximum), t score 19-77. Higher scores indicate higher functioning.
1 year
Changes in performance on Trail Making Test (A+B)
Time Frame: 1 year
Change in Trail Making Test (A+B) score as a measure of visual attention and task switching in those on standard care compared to those on intensive treatment for periodontitis. Range: 10-400 seconds; t score 19-77. Lower times indicate higher functioning.
1 year
Changes in performance on Controlled Oral Word Association Test
Time Frame: 1 year
Change in Controlled Oral Word Association Test as a measure of verbal fluency score in those on standard care compared to those on intensive treatment for periodontitis. Total raw score : 0 (minimum)-90 (maximum); t score 19-77. Higher scores indicate higher functioning.
1 year
Changes in performance on Boston Naming Test
Time Frame: 1 year
Change in Boston Naming Test score as a measure of confrontational word retrieval in those on standard care compared to those on intensive treatment for periodontitis. Total raw score : 0 (minimum)-60 (maximum); t score 19-77. Higher scores indicate higher functioning.
1 year
Changes in performance on Modified Wisconsin Card Sorting Test
Time Frame: 1 year
Change in Modified Wisconsin Card Sorting Test score as a measure of abstract reasoning ability in those on standard care compared to those on intensive treatment for periodontitis. Number of categories score : 0 (minimum)-6(maximum); t score 19-77. Higher scores indicate higher functioning.
1 year
Changes in performance on Grooved Pegboard Test
Time Frame: 1 year
Change in Grooved Pegboard Test score as a measure of visual-motor coordination in those on standard care compared to those on intensive treatment for periodontitis. Range: 10-500 seconds; t score 19-77. Lower times indicate higher functioning.
1 year
Changes in Composite Cognitive Function Score
Time Frame: 1 year
Change in composite cognitive function in those on standard care compared to those on intensive treatment for periodontitis. T scores (19-77) of individual neuropsychological tests will be averaged to compute composite scores. Neuropsychological tests include: Digit span, Hopkins Verbal Learning Test, Brief Visuospatial Memory test, Trail Making Test (A+B), Controlled Oral Word Association Test, Grooved Pegboard Test, Boston Naming Test, Modified Wisconsin Card Sorting Test.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Maryland, Baltimore

Collaborators

University of Maryland, College Park
Baltimore VA Medical Center

Investigators

  • Study Director: Kimberlly Nordstrom, CCRC, University of Maryland, College Park

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 8, 2019

Primary Completion (ACTUAL)

February 21, 2021

Study Completion (ACTUAL)

February 25, 2021

Study Registration Dates

First Submitted

November 12, 2018

First Submitted That Met QC Criteria

November 26, 2018

First Posted (ACTUAL)

November 28, 2018

Study Record Updates

Last Update Posted (ACTUAL)

July 23, 2021

Last Update Submitted That Met QC Criteria

July 16, 2021

Last Verified

July 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HP-00082777

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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