Stimulation of Cingulo-opercular Alertness Network (SCAN)
Primary Purpose
Lewy Body Disease, Lewy Body Variant of Alzheimer Disease, Lewy Body Dementia With Behavioral Disturbance
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
HD-tDCS
Sponsored by
About this trial
This is an interventional treatment trial for Lewy Body Disease focused on measuring Lewy Body Dementia, Cognitive, Thinking, Cognition, Cognitive Rehabilitation, Brain Stimulation, Imaging, Lewy Body, Dementia
Eligibility Criteria
Inclusion Criteria:
- LBD patients (DLB or PDD) who have cognitive fluctuations and who are on stable doses of cholinesterase inhibitors (i.e., at least 4 weeks) will be recruited to participate in this study.
- DLB patients will meet the Fourth consensus report of the DLB Consortium inclusion criteria for probable DLB.
- Subjects will be identified according to the following recognized DLB features: spontaneous parkinsonian motor signs, fluctuating attention and concentration, recurrent well-formed visual hallucinations, presence of REM behavioral sleep disturbance, anosmia/hyposmia,or autonomic dysfunction.
- PDD patients will meet the criteria by Emre et al. (Cognitive deficits in at least two of four of the following cognitive domains: Impaired attention, impaired executive functions, impairment in visuo-spatial functions, impaired free recall memory typically improved with cuing. Must also meet criteria for at least one behavioral symptom: apathy, depressed or anxious mood, hallucinations, delusions, excessive daytime sleepiness). Lack of behavioral symptoms does not exclude the diagnosis. Must also have none of Group III features present: (1) Co-existance of any other abnormality which might cause impairment, but judged not to be the cause of dementia. (2) Time interval between development of motor and cognitive symptoms not known. Must also have none of Group IV symptoms present: (1) Cognitive and behavioral symptoms appear solely in the context of other conditions such as acute confusion caused by systemic diseases or abnormalities, drug intoxication, or major depression according to DSM IV. (2) Features compatible with Probable Vascular Dementia criteria accordingly to NINDS-AIREN.
Exclusion Criteria:
- Subjects with contra-indications to MR imaging and/or tDCS, including pacemakers or claustrophobia
- Evidence of large vessel stroke or mass lesion on MRI
- Use of anti-cholinergic or neuroleptic drugs
- Evidence of atypical parkinsonism on neurological exam
- Major psychiatric illness, such as bipolar disorder
- Neurological conditions such as epilepsy, stroke, multiple sclerosis, or moderate to severe brain injury
- Sensory impairments that significantly limit one's ability to see or hear
- A significant history of recent alcohol or drug dependence
- Previous major radiation exposure
- Pregnancy
Sites / Locations
- 4251 Plymouth Road (University of Michigan)Recruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Experimental: HD-tDCS
Arm Description
Maximum 4 milliAmp (mA) per channel of HD-tDCS treatment for 20 minutes, for 10 sessions. Total mA dose determined by individualized computational models.
Outcomes
Primary Outcome Measures
Change from Baseline on Dementia Cognitive Fluctuations Scale
17-item subjective report of cognitive fluctuations, developed to address limitations in prior scales and has good test-retest and inter-rater reliability. Total scores range from 4 to 20, with higher scores indicating greater cognitive fluctuations.
Secondary Outcome Measures
Change from Baseline Resting State fMRI
Graph theory analysis or comparable methods will be used to identify changes in cerebral connectivity.
Full Information
NCT ID
NCT04817891
First Posted
March 23, 2021
Last Updated
September 1, 2023
Sponsor
University of Michigan
Collaborators
National Institute on Aging (NIA)
1. Study Identification
Unique Protocol Identification Number
NCT04817891
Brief Title
Stimulation of Cingulo-opercular Alertness Network
Acronym
SCAN
Official Title
Cholinergic Functions and Modulation of the Cingulo-opercular Alertness Network in LBD
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 3, 2021 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan
Collaborators
National Institute on Aging (NIA)
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.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Fluctuations in alertness are very common in persons with Lewy body dementias and are a major source of disability. Changes in a chemical messenger molecule called acetylcholine within certain brain regions may play a role in these fluctuations. We propose to test this hypothesis and also determine whether a non-invasive way of stimulating affected brain regions may be of relevance for future management of these fluctuations.
Detailed Description
The central premise of the research study is that cholinergic system changes in specific neural network regions underlie cognitive fluctuations in patients with LBD. The cingulo-opercular task control (COTC) neural network is believed to play a role in maintenance of alertness but this remains uncertain in LDB. This critical knowledge gap forms the basis of our first aim. The study proposes to use transcranial direct current stimulation (tDCS) to "excite" critical cholinergic denervation components of the COTC as an adjunct to cholinergic pharmacotherapy in a target engagement study. tDCS is an emerging non-invasive neurostimulation technology that may improve a range of neurological symptoms, including cognition. The study will evaluate whether target engagement by tDCS excitation of cholinergic denervated COTC hubs may affect cognitive fluctuations in LBD subjects.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lewy Body Disease, Lewy Body Variant of Alzheimer Disease, Lewy Body Dementia With Behavioral Disturbance
Keywords
Lewy Body Dementia, Cognitive, Thinking, Cognition, Cognitive Rehabilitation, Brain Stimulation, Imaging, Lewy Body, Dementia
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Eligible participants receive individualized intervention/stimulation based on their fMRI and PET imaging.
Masking
None (Open Label)
Masking Description
Investigator, Outcomes Assessor, and Participant/Care Provider will all know the participant is receiving intervention/stimulation. There is no placebo condition.
Allocation
N/A
Enrollment
18 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental: HD-tDCS
Arm Type
Experimental
Arm Description
Maximum 4 milliAmp (mA) per channel of HD-tDCS treatment for 20 minutes, for 10 sessions. Total mA dose determined by individualized computational models.
Intervention Type
Device
Intervention Name(s)
HD-tDCS
Intervention Description
Participants will receive HD-tDCS at up to 4 mA per channel for 20 minutes for 10 sessions. Dose determined through individualized computational models.
Primary Outcome Measure Information:
Title
Change from Baseline on Dementia Cognitive Fluctuations Scale
Description
17-item subjective report of cognitive fluctuations, developed to address limitations in prior scales and has good test-retest and inter-rater reliability. Total scores range from 4 to 20, with higher scores indicating greater cognitive fluctuations.
Time Frame
Baseline and Post-Testing (3-4 weeks)
Secondary Outcome Measure Information:
Title
Change from Baseline Resting State fMRI
Description
Graph theory analysis or comparable methods will be used to identify changes in cerebral connectivity.
Time Frame
Baseline and Post-Testing (3-4 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
LBD patients (DLB or PDD) who have cognitive fluctuations and who are on stable doses of cholinesterase inhibitors (i.e., at least 4 weeks) will be recruited to participate in this study.
DLB patients will meet the Fourth consensus report of the DLB Consortium inclusion criteria for probable DLB.
Subjects will be identified according to the following recognized DLB features: spontaneous parkinsonian motor signs, fluctuating attention and concentration, recurrent well-formed visual hallucinations, presence of REM behavioral sleep disturbance, anosmia/hyposmia,or autonomic dysfunction.
PDD patients will meet the criteria by Emre et al. (Cognitive deficits in at least two of four of the following cognitive domains: Impaired attention, impaired executive functions, impairment in visuo-spatial functions, impaired free recall memory typically improved with cuing. Must also meet criteria for at least one behavioral symptom: apathy, depressed or anxious mood, hallucinations, delusions, excessive daytime sleepiness). Lack of behavioral symptoms does not exclude the diagnosis. Must also have none of Group III features present: (1) Co-existance of any other abnormality which might cause impairment, but judged not to be the cause of dementia. (2) Time interval between development of motor and cognitive symptoms not known. Must also have none of Group IV symptoms present: (1) Cognitive and behavioral symptoms appear solely in the context of other conditions such as acute confusion caused by systemic diseases or abnormalities, drug intoxication, or major depression according to DSM IV. (2) Features compatible with Probable Vascular Dementia criteria accordingly to NINDS-AIREN.
Exclusion Criteria:
Subjects with contra-indications to MR imaging and/or tDCS, including pacemakers or claustrophobia
Evidence of large vessel stroke or mass lesion on MRI
Use of anti-cholinergic or neuroleptic drugs
Evidence of atypical parkinsonism on neurological exam
Major psychiatric illness, such as bipolar disorder
Neurological conditions such as epilepsy, stroke, multiple sclerosis, or moderate to severe brain injury
Sensory impairments that significantly limit one's ability to see or hear
A significant history of recent alcohol or drug dependence
Previous major radiation exposure
Pregnancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Isha Ghosh, BS
Phone
734-936-1035
Email
isghosh@med.umich.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Eileen Robinson
Phone
734-763-1356
Email
robinsoe@med.umich.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benjamin Hampstead, PhD
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
4251 Plymouth Road (University of Michigan)
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eileen Robinson
Phone
734-763-1356
Email
mailto:robinsoe@med.umich.edu
12. IPD Sharing Statement
Plan to Share IPD
No
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