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Dental Carotid Cognitive Study

Primary Purpose

Carotid Stenosis, Mild Cognitive Impairment, Periodontitis

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Standard Treatment
Intensive Treatment
Sponsored by
University of Maryland, Baltimore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Carotid Stenosis focused on measuring carotid stenosis cognitive function periodontitis

Eligibility Criteria

60 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Maryland - Administrative Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard treatment (control)

Intensive Treatment

Arm Description

Dental evaluation and dental prophylaxis at baseline, 3, 6, and 9 months and standard oral hygiene instruction.

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.

Outcomes

Primary Outcome Measures

Changes in performance on Montreal Cognitive Assessment (MoCA)
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.

Secondary Outcome Measures

Presence of oral bacteria in saliva and dental plaque samples
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.
Presence of bacteria in stool samples
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.
Systemic inflammation
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.
Change from baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Metabolic Measure of Standard Uptake Value Ratio (SUVR)
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.
Changes in performance on Wechsler Adult Intelligence Scale (WAIS)-III Digit Span subtest
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
Changes in performance on Hopkins Verbal Learning Test
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.
Changes in performance on Brief Visuospatial Memory test
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.
Changes in performance on Trail Making Test (A+B)
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.
Changes in performance on Controlled Oral Word Association Test
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.
Changes in performance on Boston Naming Test
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.
Changes in performance on Modified Wisconsin Card Sorting Test
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.
Changes in performance on Grooved Pegboard Test
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.
Changes in Composite Cognitive Function Score
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.

Full Information

First Posted
November 12, 2018
Last Updated
July 16, 2021
Sponsor
University of Maryland, Baltimore
Collaborators
University of Maryland, College Park, Baltimore VA Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT03755362
Brief Title
Dental Carotid Cognitive Study
Official Title
Treatment of Periodontitis to Prevent Dementia in Older Adults With Asymptomatic Carotid Artery Stenosis and Mild Cognitive Impairment
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Terminated
Why Stopped
The COVID-19 pandemic has disrupted our ability to continue this study. Follow-up visits were missed to the COVID-19 pandemic restrictions. We have elected to close enrollment and stop follow-up visits.
Study Start Date
April 8, 2019 (Actual)
Primary Completion Date
February 21, 2021 (Actual)
Study Completion Date
February 25, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland, Baltimore
Collaborators
University of Maryland, College Park, Baltimore VA Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carotid Stenosis, Mild Cognitive Impairment, Periodontitis
Keywords
carotid stenosis cognitive function periodontitis

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
This study will randomize 60 subjects ≥65 years old with asymptomatic carotid artery stenosis (ACAS), mild to moderate cognitive impairment and periodontitis. These 60 patients will be randomized to two groups (intensive vs. standardized periodontal treatment). As randomization will be computer generated, the likelihood of randomization to either group is 50:50.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard treatment (control)
Arm Type
Active Comparator
Arm Description
Dental evaluation and dental prophylaxis at baseline, 3, 6, and 9 months and standard oral hygiene instruction.
Arm Title
Intensive Treatment
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Standard Treatment
Intervention Description
Dental evaluation at baseline, 3, 6, and 9 months.
Intervention Type
Procedure
Intervention Name(s)
Intensive Treatment
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes in performance on Montreal Cognitive Assessment (MoCA)
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Presence of oral bacteria in saliva and dental plaque samples
Description
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.
Time Frame
1 year
Title
Presence of bacteria in stool samples
Description
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.
Time Frame
1 year
Title
Systemic inflammation
Description
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.
Time Frame
1 year
Title
Change from baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Metabolic Measure of Standard Uptake Value Ratio (SUVR)
Description
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.
Time Frame
1 year
Title
Changes in performance on Wechsler Adult Intelligence Scale (WAIS)-III Digit Span subtest
Description
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
Time Frame
1 year
Title
Changes in performance on Hopkins Verbal Learning Test
Description
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.
Time Frame
1 year
Title
Changes in performance on Brief Visuospatial Memory test
Description
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.
Time Frame
1 year
Title
Changes in performance on Trail Making Test (A+B)
Description
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.
Time Frame
1 year
Title
Changes in performance on Controlled Oral Word Association Test
Description
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.
Time Frame
1 year
Title
Changes in performance on Boston Naming Test
Description
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.
Time Frame
1 year
Title
Changes in performance on Modified Wisconsin Card Sorting Test
Description
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.
Time Frame
1 year
Title
Changes in performance on Grooved Pegboard Test
Description
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.
Time Frame
1 year
Title
Changes in Composite Cognitive Function Score
Description
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.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kimberlly Nordstrom, CCRC
Organizational Affiliation
University of Maryland, College Park
Official's Role
Study Director
Facility Information:
Facility Name
University of Maryland - Administrative Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States

12. IPD Sharing Statement

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Dental Carotid Cognitive Study

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