PLUG Dementia Trial and MRI PLUG Dementia Sub-Study

Overall and MRI-based Impact of Percutaneous Left Atrial Appendage Closure on the Cognitive Decline and Dementia in Patients With Atrial Fibrillation (PLUG Dementia Trial and MRI PLUG Dementia Sub-Study)

PLUG Dementia Trial:

Patients will be screened at Intermountain Medical Center and at Intermountain affiliated anticoagulation clinics in the Salt Lake City region. Patients with atrial fibrillation that undergo a standard of care, clinically approved, left atrial appendage closure will be considered for study. All patients will be followed for 24 months, and will be assessed at the 3-, 6-, 12-, 18- and 24-months post-left atrial appendage closure as well as other visits deemed necessary for clinical care. All subjects will undergo protocol-specified laboratory tests and will complete 6 standard, validated questionnaires at each follow-up visit, except at the 3-month visit when only one questionnaire will be administered. A subset of patients (n=20), will receive a cranial MRI at baseline and 24-month visit.

MRI PLUG Dementia Sub-Study:

In addition to the above, 20 of the 60 subjects who are selected for participation in this sub-study will receive a cranial MRI at baseline and at the 2-year (24 months) follow-up visit.

Study Overview

• Status: Terminated
• Conditions: Atrial Fibrillation; Dementia; Cognitive Decline
• Intervention / Treatment: Other: Questionnaire; Diagnostic test: Magnetic Resonance Imaging

• Study Type: Observational
• Enrollment (Actual): 22

Contacts and Locations

Study Locations

• United States
  • Utah
    • Murray, Utah, United States, 84143
      • Intermountain Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with atrial fibrillation that undergo a standard of care, clinically approved, left atrial appendage closure will be considered for study.

Description

Inclusion Criteria:

1. Male or female >65 years of age
2. Atrial fibrillation documented by electrocardiogram, ambulatory event monitor, or telemetry within 6 months of enrollment
3. Moderate risk of thromboembolism based upon a CHADS2 score or CHADS2 Vasc score of ≥2.
4. Recipient of a left atrial appendage closure device within 3 months of enrollment (within 6 months, for patients considered for the MRI PLUG Dementia Sub-Study)
5. Have the ability to complete a mini-mental status evaluation
6. Have the ability to independently comprehend and complete a quality of life and dementia questionnaires.
7. Ability to provide informed consent for study participation
8. Willing and able to comply with the prescribed follow-up tests and schedule of evaluations.

Exclusion Criteria:

1. Have a history of any form of dementia
2. Have a life expectancy less than 24 months
3. Are unable to comply with the follow-up schedule
4. An upper age limit not to be used if participation inclusion criteria are met.
5. Participation in any other clinical trials involving an investigational or marketed drug within 30 days prior to entry in this study;
6. Other conditions that in the opinion of the Principal Investigator may increase risk to the subject and/or compromise the quality of the clinical trial
7. The Principal Investigator(s) determine(s) that the subject is not eligible for participation in this research study.

In addition to the above exclusion criteria, patients considered for the MRI PLUG Dementia Sub-Study will be excluded if the patient -

1. Does not receive a left atrial appendage closure device
2. Has contraindication towards the MRI scan (presence of a nonconditional cardiac implantable device, a history of metallic implants, shrapnel, neurosurgical clip placement)
3. Has conditional cardiac MRI cardiac implantable device, joint replacements, coronary stents, ASD/PFO closure devices, sternal wires or most prosthetic heart valves
4. Has severe renal dysfunction, defined as a creatinine clearance <15 mL/min (documented within the last 3 months)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PLUG Dementia Trial; Patients with atrial fibrillation that undergo a standard of care, clinically approved, left atrial appendage closure will be considered for study. All patients will be followed for 24 months, and will be assessed at the 3-, 6-, 12-, 18- and 24-months post-left atrial appendage closure as well as other visits deemed necessary for clinical care. All subjects will undergo protocol-specified laboratory tests and will complete 6 standard, validated questionnaires at each follow-up visit, except at the 3-month visit when only one questionnaire will be administered.	Other: Questionnaire; Alzheimer's Disease Assessment Scale (ADAS-cog11) and Disability Assessment for Dementia (DAD) Questionnaires
MRI PLUG Dementia Sub-Study; 20 of the 60 subjects who are selected for participation in this sub-study will receive a cranial MRI at baseline and at the 2-year (24 months) follow-up visit.	Diagnostic test: Magnetic Resonance Imaging; MRI at baseline and at 24 months post-enrollment for 20 sub-study participants

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dementia Incidence	Incident dementia determined by a formal diagnosis by a neurologist.	24 months
Change in cognitive decline	Moderate cognitive decline defined as a 30% decrease in Alzheimer's Disease Assessment Scale score or those with a score <50% or a 30% change on the Disability Assessment for Dementia.	24 months
Incidence of baseline micro- and macro-cerebral ischemic events (Sub-study Participants)	assess the incidence of baseline micro- and macro-cerebral ischemic events (both bleeds and clots) at the time of left atrial appendage closure and compare this with a serial study.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in cranial MRI	Incidence of bleeding and/or clots in the brain.	24 months

Collaborators and Investigators

• Sponsor: Intermountain Health Care, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2017
• Primary Completion (Actual): January 8, 2021
• Study Completion (Actual): January 8, 2021

Study Registration Dates

• First Submitted: March 15, 2017
• First Submitted That Met QC Criteria: March 24, 2017
• First Posted (Actual): March 27, 2017

Study Record Updates

• Last Update Posted (Actual): April 5, 2021
• Last Update Submitted That Met QC Criteria: April 1, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Arrhythmias, Cardiac; Cognition Disorders; Atrial Fibrillation; Dementia; Cognitive Dysfunction
• Other Study ID Numbers: 1050344

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No