Repetitive Transcranial Magnetic Stimulation for Dementia (rTMS for demen)
Primary Purpose
Dementia, Mild Cognitive Impairment
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
RTMS
sham
Sponsored by
About this trial
This is an interventional treatment trial for Dementia focused on measuring dementia, Mild Cognitive Impairment (MCI), RTMS, CVLT
Eligibility Criteria
Inclusion Criteria:
- Veterans aged 55 years or older
- Diagnosed with Mild Cognitive Impairment (MCI) or dementia likely due to Alzheimer's disease.
- Ability to obtain a Motor Threshold, determined during the screening process.
- With an adequately stable condition and living environment to enable attendance at scheduled clinic visits.
- If on a prescription medication for cognition that medication dose will be stable for at least 4 weeks prior to randomization into the study and participant will be willing to remain on a stable regimen during the acute treatment phase.
- Able to read, verbalize understanding, and voluntarily sign the Informed Consent Form to be signed by the participant, or a designated legal representative when the participant lacks decision making capacity prior to participating in any study- specific procedures or assessments.
Exclusion Criteria:
- Patients with prior exposure to rTMS or electroconvulsive therapy (ECT).
- Unable to safely withdraw, at least two weeks prior to treatment commencement, from medications that substantially increase the risk of having seizures.
- Have a cardiac pacemaker or a cochlear implant.
- Have an implanted device deep brain stimulation or metal in the brain
- Current substance abuse not including caffeine or nicotine as determined by patient report or chart review.
- Active current suicidal intent or plan as determined by patient report or chart review.
- Current or Prior history of a seizure disorder as determined by patient report or chart review
- Traumatic brain injury within the last two months
- Participation in another concurrent interventional clinical trial
- Known current psychosis as determined by patient report or chart review.
- Current or prior history of a mass lesion, cerebral infarct or other non-cognitive, active central nervous system (CNS) disease that would increase the risk for seizure.
- Not fluent in English or a hearing impairment severe enough to impair comprehension
Sites / Locations
- VA Palo Alto Health Care System, Palo Alto, CA
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
RTMS
sham
Arm Description
repetitive transcranial magnetic stimulation
sham noise to block the sound of treatment
Outcomes
Primary Outcome Measures
Changes From Baseline CVLT Scores After Treatment and 4 Month Later
Changes of California verbal learning test scores (CVLT) from baseline after treatment and 4 months later.
CVLT is 16 points scoring system. (minimum=0, maximum=16, higher the better memory).
Secondary Outcome Measures
Changes in Boston Naming After Treatment
Changes in Boston Naming Test (BNT) from baseline was analyzed. BNT is a 60 points scoring system. (minimum=0, maximum=60, higher the better).
Changes in Plasma BDNF Levels After Treatment
Changes in BDNF plasma levels (pg/ml) from baseline were analyzed after treatment.
BDNF is a plasma biomarker, minimum=0, no maximum. Higher number means more BDNF synthesis).
Changes in Animal Fluency After Treatment and 4 Months Later
Animal Fluency (AF) is a scoring system to assess the ability to generate a list of related words.
The score is the number of animals the examinee can name in one minute time. (Minimum = 0, No maximum, higher the better).
Changes in Trail Making B Test Score After Treatment and 4 Months Later
Trail making B is a scoring system for the assessment of the mental flexibility, processing speed and executive function. The score is the time (in seconds) it takes for the examinee to draw line segments connecting sequentially from 1-A-2-B-3....all the way to12-L-13. (The lower score means faster speed and means better performance. The minimum is (hypothetically) zero. There is no maximum. However, in some test centers, the maximum allowed time is 200 seconds.
Brief Visual Memory Test (BVMT)
A piece of paper with 6 simple drawings is presented to the subject for 10 seconds. The subject is then asked to draw these drawings from memory. The process is repeated three times to assess visual memory and learning. Each correct drawing scores two pints. Maximum score for three trials is 36. Minimum score is 0. Higher the better.
Montreal Cognitive Assessment (MoCA)
MoCA is a one page, 30 point cognitive screening test. It test the following cognitive domains:
short-term memory (5 points)- two learning trials of five nouns and delayed recall after approximately five minutes.
visuospatial abilities - clock-drawing task (3 points) and copy a cube (1 point).
executive functions - alternation task abbreviated trail-making B (1 point), and a two-item verbal abstraction task (2 points).
attention, concentration, and working memory - a sustained attention task (target detection using tapping; 1 point), a serial subtraction task (3 points), and digits forward and backward (1 point each).
language - three-item confrontation naming (3 points), repetition of two sentences (2 points), and verbal fluency (1 point).
abstract reasoning - describe the similarity of tasks (2 points).
orientation to time and place (6 points). Minimum score: 0. Maximum score: 30. Higher the better.
Full Information
NCT ID
NCT02621424
First Posted
November 23, 2015
Last Updated
November 2, 2022
Sponsor
VA Office of Research and Development
1. Study Identification
Unique Protocol Identification Number
NCT02621424
Brief Title
Repetitive Transcranial Magnetic Stimulation for Dementia
Acronym
rTMS for demen
Official Title
Repetitive Transcranial Magnetic Stimulation for Dementia
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 1, 2016 (Actual)
Primary Completion Date
February 28, 2019 (Actual)
Study Completion Date
October 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development
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
The purpose is to is to study if repetitive transcranial magnetic stimulation (rTMS) improves cognitive function in patients with neurodegenerative conditions which may manifest as mild to moderate cognitive impairment and, in late phase, dementia. This study also intends to investigate if the responses to rTMS intervention are either positively or negatively correlated with the initial severity of cognitive impairment.
Detailed Description
The primary hypothesis is that rTMS applied to the dorsolateral prefrontal cortex will lead to improved memory, language and executive function compared to patients who receive a sham, control treatment. The improvement is defined as having higher performance on the California Verbal Learning Test (CVLT-II). Secondary Hypotheses are that:
1: rTMS- will lead to higher performance on secondary cognitive measures relating to executive function and naming compared to performance by participants in the sham treatment group at the termination of treatment; and that
2: rTMS-induced memory improvement parallels changes in serum and cerebrospinal fluid (CSF) brain-derived neurotrophic factor (BDNF) levels after treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dementia, Mild Cognitive Impairment
Keywords
dementia, Mild Cognitive Impairment (MCI), RTMS, CVLT
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RTMS
Arm Type
Experimental
Arm Description
repetitive transcranial magnetic stimulation
Arm Title
sham
Arm Type
Sham Comparator
Arm Description
sham noise to block the sound of treatment
Intervention Type
Device
Intervention Name(s)
RTMS
Intervention Description
stimulation of the brain with magnetic pulses
Intervention Type
Device
Intervention Name(s)
sham
Intervention Description
sham noise to block the sound of stimulation
Primary Outcome Measure Information:
Title
Changes From Baseline CVLT Scores After Treatment and 4 Month Later
Description
Changes of California verbal learning test scores (CVLT) from baseline after treatment and 4 months later.
CVLT is 16 points scoring system. (minimum=0, maximum=16, higher the better memory).
Time Frame
Assessed at baseline, end of treatment, and 4-month post-treatment follow up
Secondary Outcome Measure Information:
Title
Changes in Boston Naming After Treatment
Description
Changes in Boston Naming Test (BNT) from baseline was analyzed. BNT is a 60 points scoring system. (minimum=0, maximum=60, higher the better).
Time Frame
Assessed at baseline, end of treatment, and 4-month post-treatment follow up
Title
Changes in Plasma BDNF Levels After Treatment
Description
Changes in BDNF plasma levels (pg/ml) from baseline were analyzed after treatment.
BDNF is a plasma biomarker, minimum=0, no maximum. Higher number means more BDNF synthesis).
Time Frame
within a week following the last treatment session and 4 months later
Title
Changes in Animal Fluency After Treatment and 4 Months Later
Description
Animal Fluency (AF) is a scoring system to assess the ability to generate a list of related words.
The score is the number of animals the examinee can name in one minute time. (Minimum = 0, No maximum, higher the better).
Time Frame
Assessed at baseline, end of treatment, and 4-month post-treatment follow up
Title
Changes in Trail Making B Test Score After Treatment and 4 Months Later
Description
Trail making B is a scoring system for the assessment of the mental flexibility, processing speed and executive function. The score is the time (in seconds) it takes for the examinee to draw line segments connecting sequentially from 1-A-2-B-3....all the way to12-L-13. (The lower score means faster speed and means better performance. The minimum is (hypothetically) zero. There is no maximum. However, in some test centers, the maximum allowed time is 200 seconds.
Time Frame
Assessed at baseline, end of treatment, and 4-month post-treatment follow up
Title
Brief Visual Memory Test (BVMT)
Description
A piece of paper with 6 simple drawings is presented to the subject for 10 seconds. The subject is then asked to draw these drawings from memory. The process is repeated three times to assess visual memory and learning. Each correct drawing scores two pints. Maximum score for three trials is 36. Minimum score is 0. Higher the better.
Time Frame
assessed at baseline, end of treatment and 4-month post-treatment follow up
Title
Montreal Cognitive Assessment (MoCA)
Description
MoCA is a one page, 30 point cognitive screening test. It test the following cognitive domains:
short-term memory (5 points)- two learning trials of five nouns and delayed recall after approximately five minutes.
visuospatial abilities - clock-drawing task (3 points) and copy a cube (1 point).
executive functions - alternation task abbreviated trail-making B (1 point), and a two-item verbal abstraction task (2 points).
attention, concentration, and working memory - a sustained attention task (target detection using tapping; 1 point), a serial subtraction task (3 points), and digits forward and backward (1 point each).
language - three-item confrontation naming (3 points), repetition of two sentences (2 points), and verbal fluency (1 point).
abstract reasoning - describe the similarity of tasks (2 points).
orientation to time and place (6 points). Minimum score: 0. Maximum score: 30. Higher the better.
Time Frame
Assessed at baseline, end of treatment, and 4-month post-treatment follow up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Veterans aged 55 years or older
Diagnosed with Mild Cognitive Impairment (MCI) or dementia likely due to Alzheimer's disease.
Ability to obtain a Motor Threshold, determined during the screening process.
With an adequately stable condition and living environment to enable attendance at scheduled clinic visits.
If on a prescription medication for cognition that medication dose will be stable for at least 4 weeks prior to randomization into the study and participant will be willing to remain on a stable regimen during the acute treatment phase.
Able to read, verbalize understanding, and voluntarily sign the Informed Consent Form to be signed by the participant, or a designated legal representative when the participant lacks decision making capacity prior to participating in any study- specific procedures or assessments.
Exclusion Criteria:
Patients with prior exposure to rTMS or electroconvulsive therapy (ECT).
Unable to safely withdraw, at least two weeks prior to treatment commencement, from medications that substantially increase the risk of having seizures.
Have a cardiac pacemaker or a cochlear implant.
Have an implanted device deep brain stimulation or metal in the brain
Current substance abuse not including caffeine or nicotine as determined by patient report or chart review.
Active current suicidal intent or plan as determined by patient report or chart review.
Current or Prior history of a seizure disorder as determined by patient report or chart review
Traumatic brain injury within the last two months
Participation in another concurrent interventional clinical trial
Known current psychosis as determined by patient report or chart review.
Current or prior history of a mass lesion, cerebral infarct or other non-cognitive, active central nervous system (CNS) disease that would increase the risk for seizure.
Not fluent in English or a hearing impairment severe enough to impair comprehension
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jauhtai J Cheng, MD
Organizational Affiliation
VA Palo Alto Health Care System, Palo Alto, CA
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Palo Alto Health Care System, Palo Alto, CA
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304-1290
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34958013
Citation
Cheng J, Fairchild JK, McNerney MW, Noda A, Ashford JW, Suppes T, Chao SZ, Taylor J, Rosen AC, Durazzo TC, Lazzeroni LC, Yesavage J. Repetitive Transcranial Magnetic Stimulation as a Treatment for Veterans with Cognitive Impairment and Multiple Comorbidities. J Alzheimers Dis. 2022;85(4):1593-1600. doi: 10.3233/JAD-210349.
Results Reference
derived
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Repetitive Transcranial Magnetic Stimulation for Dementia
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