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Dental Carotid Cognitive Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03755362
Recruitment Status : Active, not recruiting
First Posted : November 28, 2018
Last Update Posted : November 13, 2020
Sponsor:
Collaborators:
University of Maryland, College Park
Baltimore VA Medical Center
Information provided by (Responsible Party):
Brajesh Lal, University of Maryland, Baltimore

Tracking Information
First Submitted Date  ICMJE November 12, 2018
First Posted Date  ICMJE November 28, 2018
Last Update Posted Date November 13, 2020
Actual Study Start Date  ICMJE April 8, 2019
Estimated Primary Completion Date October 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 26, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 27, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 26, 2018)
  • 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.
  • 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.
  • Systemic inflammation [ Time Frame: 1 year ]
    Differences in inflammatory markers such as IL-6 and 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) [ 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 neurospychological 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dental Carotid Cognitive Study
Official Title  ICMJE Treatment of Periodontitis to Prevent Dementia in Older Adults With Asymptomatic Carotid Artery Stenosis and Mild Cognitive Impairment
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Prevention
Condition  ICMJE
  • Carotid Stenosis
  • Mild Cognitive Impairment
  • Periodontitis
Intervention  ICMJE
  • Procedure: Standard Treatment
    Dental evaluation at baseline, 3, 6, and 9 months.
  • 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.
Study Arms  ICMJE
  • Active Comparator: Standard treatment (control)
    Dental evaluation and dental prophylaxis at baseline, 3, 6, and 9 months and standard oral hygiene instruction.
    Intervention: Procedure: Standard Treatment
  • 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.
    Intervention: Procedure: Intensive Treatment
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: November 26, 2018)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2021
Estimated Primary Completion Date October 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03755362
Other Study ID Numbers  ICMJE HP-00082777
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Brajesh Lal, University of Maryland, Baltimore
Study Sponsor  ICMJE University of Maryland, Baltimore
Collaborators  ICMJE
  • University of Maryland, College Park
  • Baltimore VA Medical Center
Investigators  ICMJE
Study Director: Kimberlly Nordstrom, CCRC University of Maryland, College Park
PRS Account University of Maryland, Baltimore
Verification Date November 2020

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