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Dental Carotid Cognitive Study

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ClinicalTrials.gov Identifier: NCT03755362
Recruitment Status : Recruiting
First Posted : November 28, 2018
Last Update Posted : September 12, 2019
Sponsor:
Collaborators:
University of Maryland, College Park
Baltimore VA Medical Center
Information provided by (Responsible Party):
Brajesh Lal, University of Maryland, Baltimore

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.

Condition or disease Intervention/treatment Phase
Carotid Stenosis Mild Cognitive Impairment Periodontitis Procedure: Standard Treatment Procedure: Intensive Treatment Not Applicable

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


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
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
Official Title: Treatment of Periodontitis to Prevent Dementia in Older Adults With Asymptomatic Carotid Artery Stenosis and Mild Cognitive Impairment
Actual Study Start Date : April 8, 2019
Estimated Primary Completion Date : October 31, 2020
Estimated Study Completion Date : October 31, 2021

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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03755362


Contacts
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Contact: Laila Anthony, BS 410-605-7000 ext 55556 lganthony@som.umaryland.edu

Locations
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United States, Maryland
University of Maryland - Administrative Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Kimberlly A Nordstrom, CCRC    410-706-3941    knordstrom@som.umaryland.edu   
Principal Investigator: Brajesh K Lal, MD         
Sponsors and Collaborators
University of Maryland, Baltimore
University of Maryland, College Park
Baltimore VA Medical Center
Investigators
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Study Director: Kimberlly Nordstrom, CCRC University of Maryland, College Park

Publications:
Fouad A, Mongodin E, Hittle L, et al. Microbiome analysis of oral and atheromatous plaques in atherosclerotic patients. In: IADR General Session and Exhibition. 2014

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Responsible Party: Brajesh Lal, Study Principal Investigator, University of Maryland, Baltimore
ClinicalTrials.gov Identifier: NCT03755362     History of Changes
Other Study ID Numbers: HP-00082777
First Posted: November 28, 2018    Key Record Dates
Last Update Posted: September 12, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Brajesh Lal, University of Maryland, Baltimore:
carotid stenosis cognitive function periodontitis
Additional relevant MeSH terms:
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Periodontitis
Carotid Stenosis
Constriction, Pathologic
Cognitive Dysfunction
Pathological Conditions, Anatomical
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Periodontal Diseases
Mouth Diseases
Stomatognathic Diseases
Carotid Artery Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases