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rTMS in Older Adults With MCI and AUD

Primary Purpose

Alcohol Use Disorder, Mild Cognitive Impairment, Transcranial Magnetic Stimulation

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Active, Open Label iTBS-rTMS
Sponsored by
Medical University of South Carolina
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcohol Use Disorder

Eligibility Criteria

60 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age 60-85. English as a first/primary language. Current alcohol use disorder Alcohol consumption of at least 4 heavy drinking days (defined as ≥ 4 drinks for women and ≥ 5 for men) per week during the 30-days prior to enrolling; Meets actuarial neuropsychological criteria for MCI: ≥2 impaired scores within one cognitive domain, or ≥1 impaired scores in ≥3 domains, where an impaired score is defined as ≤16th percentile using demographically-corrected norms. Not pregnant (will administer pregnancy test to confirm) Functional visual and auditory acuity to complete all assessments. Exclusion Criteria: Prior diagnosis of Dementia or Major Neurocognitive Disorder per NIA-AA or DSM-5 criteria, and TICS ≤ 22 suggestive of dementia. Current substance use disorder other than AUD or nicotine use disorder, bipolar disorder, or schizophrenia spectrum or other psychotic disorder. Daily/weekly anticholinergic or sedative use. Stimulants may be allowed pending investigator review. Cholinesterase inhibitors, NMDA receptor antagonists, and antidepressants are allowed if on a stable regimen of 4 weeks prior to enrollment. History of significant or unstable condition/s that may impact cognition such as significant cardiac, cerebrovascular, or metabolic disease, developmental disorder, or other neurologic disease (e.g. movement disorder, moderate to severe brain injury, seizures). MRI and TMS contraindications (e.g. implants, claustrophobia, conditions/treatments that lower seizure threshold, taking medications that have short half-lives, no identifiable motor threshold). Enrolled in a clinical trial or has received an investigational medication or device in the last 30 days. Pregnant (will administer pregnancy test to confirm)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Active, Open Label iTBS-rTMS

    Arm Description

    Individuals will receive 10 sessions of iTBS-rTMS per day, 5 days per week for one week (50 sessions total). All will undergo clinical assessments and brain MRI at pre-treatment and at 1-week post-treatment, and clinical assessments at 4-weeks post-treatment. Weekly post-treatment online self-report assessments will be collected up to four weeks. Resting-state parcellations of pre- and post-fMRI will be completed for personalized targeting and network parcellations.

    Outcomes

    Primary Outcome Measures

    Change in NIH Toolbox-Cognition Battery (NIHTB-CB) Fluid Composite
    The NIHTB-CB is a performance-based, iPad-administered ~30-minute suite of 7 tests that ascertain abilities in different cognitive domains (i.e. executive function, episodic memory, working memory, processing speed, language). It was developed using advanced psychometric techniques to minimize measurement error and produces normed subtest and composite scores. We will use the fully-corrected T-score (range T=0-100; Mean T=50, SD=10; higher scores indicating better cognition) of the Fluid Cognition Composite (normed for age, sex, years of education, and race/ethnicity) to more accurately reflect global, dynamic thinking abilities that reflect the presence of disease or the impact of interventions, and not premorbid influences on test scores.
    Change in Subjective Drinking
    The Alcohol Timeline Followback (TLFB-90) is a drinking assessment method that obtains estimates of daily drinking. Using a calendar, people provide retrospective estimates of their daily drinking over 90 days from the interview date. Several memory aids can be used to enhance recall (e.g., calendar; key dates serve as anchors for reporting drinking; standard drink conversion).
    Change in Network Functional Connectivity between and among cognitive and reward networks and other networks
    fMRI will be collected while participants are at rest (i.e. rs-fMRI) during the pre-treatment and post-treatment MRI sessions. The rs-fMRI data will be used to compute functional connectivity, which is the correlation between the activity in each brain region pair over the course of the scan. Each brain region belongs to 1 of 7 previously defined networks (frontoparietal: FPN; default mode: DMN; dorsal attention: DAT; ventral attention: VAT; limbic: LIM; visual: VIS; somatomotor: MOT). Functional connectivity can thus be computed for each network by taking the average of connectivity of all regions belonging to the respective network.

    Secondary Outcome Measures

    Full Information

    First Posted
    May 31, 2023
    Last Updated
    August 15, 2023
    Sponsor
    Medical University of South Carolina
    Collaborators
    National Institutes of Health (NIH), National Institute on Alcohol Abuse and Alcoholism (NIAAA)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05896332
    Brief Title
    rTMS in Older Adults With MCI and AUD
    Official Title
    Targeting the Shared Substrates of Alcohol Misuse and Cognitive Impairment: Accelerated rTMS for Older Adults With Alcohol Use Disorder
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 1, 2023 (Anticipated)
    Primary Completion Date
    July 1, 2025 (Anticipated)
    Study Completion Date
    December 1, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Medical University of South Carolina
    Collaborators
    National Institutes of Health (NIH), National Institute on Alcohol Abuse and Alcoholism (NIAAA)

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    Yes
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Alcohol misuse is a risk factor for early onset cognitive impairment, contributing to 10% of early onset dementia, with risk corresponding to consumption. Additionally, continued drinking risks worsening cognitive decline and dementia progression, while worsening cognitive impairment contributes to drinking escalation. Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve cognition in Alzheimer's Disease and Related Dimentias (ADRD) and separately reduce heavy drinking in alcohol use disorder. Our objective is to optimize rTMS for simultaneous mitigation of both drinking and cognitive dysfunction in older adults.
    Detailed Description
    Alcohol misuse is a risk factor for early onset cognitive impairment, contributing to 10% of early onset dementia, with risk corresponding to consumption. Additionally, continued drinking risks worsening cognitive decline and dementia progression, while worsening cognitive impairment contributes to drinking escalation. Notably, there exists no intervention targeting the intersection of alcohol misuse and cognitive dysfunction in older adults. It is unclear whether alcohol contributes to a specific form of Alzheimer's Disease and Related Dementias (ADRD) and furthermore whether the impairments and structural brain changes represent classical ADRD neurodegenerative patterns. Despite the unclear etiopathogenesis, there is emerging evidence that repetitive transcranial magnetic stimulation (rTMS) to upregulate executive/cognitive control circuitry can improve cognition in ADRD, and separately reduce heavy drinking in AUD. Our long-term objective is to optimize rTMS for simultaneous mitigation of both drinking and cognitive dysfunction in older adults towards breaking this cycle and thwarting progression to dementia.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Alcohol Use Disorder, Mild Cognitive Impairment, Transcranial Magnetic Stimulation

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Model Description
    We propose to conduct an open-label Phase I trial of accelerated iTBS-rTMS for AUD+MCI. We propose to recruit 35 treatment-seeking individuals ages 60-85 years, with AUD and cognitive impairment, specifically those meeting criteria for AUD with DSM-5 Mild Neurocognitive Disorder. Individuals will receive 10 sessions of iTBS-rTMS per day, 5 days per week for one week (50 sessions total). All will undergo clinical assessments and brain MRI at pre-treatment and at 1-week post-treatment, and clinical assessments at 4-weeks post-treatment. Weekly post-treatment online self-report assessments will be collected up to four weeks. Resting-state parcellations of pre- and post-fMRI will be completed for personalized targeting and network parcellations.
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    35 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Active, Open Label iTBS-rTMS
    Arm Type
    Experimental
    Arm Description
    Individuals will receive 10 sessions of iTBS-rTMS per day, 5 days per week for one week (50 sessions total). All will undergo clinical assessments and brain MRI at pre-treatment and at 1-week post-treatment, and clinical assessments at 4-weeks post-treatment. Weekly post-treatment online self-report assessments will be collected up to four weeks. Resting-state parcellations of pre- and post-fMRI will be completed for personalized targeting and network parcellations.
    Intervention Type
    Device
    Intervention Name(s)
    Active, Open Label iTBS-rTMS
    Intervention Description
    Participants in this group will receive 10 sessions of iTBS-rTMS per day, 5 days per week for one week (50 sessions total)
    Primary Outcome Measure Information:
    Title
    Change in NIH Toolbox-Cognition Battery (NIHTB-CB) Fluid Composite
    Description
    The NIHTB-CB is a performance-based, iPad-administered ~30-minute suite of 7 tests that ascertain abilities in different cognitive domains (i.e. executive function, episodic memory, working memory, processing speed, language). It was developed using advanced psychometric techniques to minimize measurement error and produces normed subtest and composite scores. We will use the fully-corrected T-score (range T=0-100; Mean T=50, SD=10; higher scores indicating better cognition) of the Fluid Cognition Composite (normed for age, sex, years of education, and race/ethnicity) to more accurately reflect global, dynamic thinking abilities that reflect the presence of disease or the impact of interventions, and not premorbid influences on test scores.
    Time Frame
    Week 0 (1 week pre-treatment), Week 2 (immediately post-treatment), Week 6 (4 weeks post-treatment)
    Title
    Change in Subjective Drinking
    Description
    The Alcohol Timeline Followback (TLFB-90) is a drinking assessment method that obtains estimates of daily drinking. Using a calendar, people provide retrospective estimates of their daily drinking over 90 days from the interview date. Several memory aids can be used to enhance recall (e.g., calendar; key dates serve as anchors for reporting drinking; standard drink conversion).
    Time Frame
    Week 0 (1 week pre-treatment), Week 2 (immediately post-treatment), Week 6 (4 weeks post-treatment)
    Title
    Change in Network Functional Connectivity between and among cognitive and reward networks and other networks
    Description
    fMRI will be collected while participants are at rest (i.e. rs-fMRI) during the pre-treatment and post-treatment MRI sessions. The rs-fMRI data will be used to compute functional connectivity, which is the correlation between the activity in each brain region pair over the course of the scan. Each brain region belongs to 1 of 7 previously defined networks (frontoparietal: FPN; default mode: DMN; dorsal attention: DAT; ventral attention: VAT; limbic: LIM; visual: VIS; somatomotor: MOT). Functional connectivity can thus be computed for each network by taking the average of connectivity of all regions belonging to the respective network.
    Time Frame
    Week 0 (1 week pre-treatment), Week 2 (immediately post-treatment),

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    60 Years
    Maximum Age & Unit of Time
    85 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age 60-85. English as a first/primary language. Current alcohol use disorder Alcohol consumption of at least 4 heavy drinking days (defined as ≥ 4 drinks for women and ≥ 5 for men) per week during the 30-days prior to enrolling; Meets actuarial neuropsychological criteria for MCI: ≥2 impaired scores within one cognitive domain, or ≥1 impaired scores in ≥3 domains, where an impaired score is defined as ≤16th percentile using demographically-corrected norms. Not pregnant (will administer pregnancy test to confirm) Functional visual and auditory acuity to complete all assessments. Exclusion Criteria: Prior diagnosis of Dementia or Major Neurocognitive Disorder per NIA-AA or DSM-5 criteria, and TICS ≤ 22 suggestive of dementia. Current substance use disorder other than AUD or nicotine use disorder, bipolar disorder, or schizophrenia spectrum or other psychotic disorder. Daily/weekly anticholinergic or sedative use. Stimulants may be allowed pending investigator review. Cholinesterase inhibitors, NMDA receptor antagonists, and antidepressants are allowed if on a stable regimen of 4 weeks prior to enrollment. History of significant or unstable condition/s that may impact cognition such as significant cardiac, cerebrovascular, or metabolic disease, developmental disorder, or other neurologic disease (e.g. movement disorder, moderate to severe brain injury, seizures). MRI and TMS contraindications (e.g. implants, claustrophobia, conditions/treatments that lower seizure threshold, taking medications that have short half-lives, no identifiable motor threshold). Enrolled in a clinical trial or has received an investigational medication or device in the last 30 days. Pregnant (will administer pregnancy test to confirm)
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Sarah Huffman, B.A.
    Phone
    843-792-5560
    Email
    huffmans@musc.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Samantha LaPorta
    Email
    laporta@musc.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Lisa McTeague, Ph.D.
    Organizational Affiliation
    Medical University of South Carolina
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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