Trial Outcomes & Findings for tACS for Amyloid-β Reduction in Alzheimer's Disease (NCT NCT03290326)

NCT ID: NCT03290326

Last Updated: 2022-08-22

Results Overview

Changes in the amyloid load observed via PET imaging will be evaluated by comparing PET data acquired before and after the 10 tACS sessions. The metric used is SUVR, a measure of the amount of proteins in the brain identified at the PET exam. We will calculate the difference between pre and post tACS SUVR (dSUVR) for the entire brain and report the average value (and standard deviation) for the entire group of patients. A negative value express a decrease in the amount of proteins in the brain post tACS intervention. It must be considered that dSUVR values refer to the entire brain, however patients were treated according to personalized tACS montages targeting patient-specific regions mostly affected by the pathology. This might have led to slightly different changes in SUVR in different part of the brain across participants. Also, as per standard procedures, results are presented at group level, i.e. without considering individual differences in longitudinal amyloid load changes.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

17 participants

Primary outcome timeframe

Up to six weeks

Results posted on

2022-08-22

Participant Flow

Of 17 enrolled participants, 10 met inclusion criteria and underwent transcranial alternating current stimulation (tACS)

During the screening and baseline procedures 7 participants screened out for the following reasons: 4 participants screened out on cognitive testing measures, being either too advanced or too mild, 2 participants did not meet 6 weeks stable medication inclusion criteria, and 1 participant screened out due to incidental findings on the baseline MRI

Participant milestones

Participant milestones
Measure
tACS
Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) was applied for 1 hour in 10 sessions on consecutive weekdays.
Overall Study
STARTED
10
Overall Study
COMPLETED
10
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

tACS for Amyloid-β Reduction in Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
tACS
n=10 Participants
Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) was applied for 1 hour in 10 sessions on consecutive weekdays.
Age, Customized
Age · 55
1 Participants
n=99 Participants
Age, Customized
Age · 57
1 Participants
n=99 Participants
Age, Customized
Age · 63
1 Participants
n=99 Participants
Age, Customized
Age · 75
1 Participants
n=99 Participants
Age, Customized
Age · 76
2 Participants
n=99 Participants
Age, Customized
Age · 78
2 Participants
n=99 Participants
Age, Customized
Age · 79
1 Participants
n=99 Participants
Age, Customized
Age · 83
1 Participants
n=99 Participants
Sex: Female, Male
Female
4 Participants
n=99 Participants
Sex: Female, Male
Male
6 Participants
n=99 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=99 Participants
Race (NIH/OMB)
Asian
0 Participants
n=99 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=99 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=99 Participants
Race (NIH/OMB)
White
10 Participants
n=99 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=99 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
Region of Enrollment
United States
10 participants
n=99 Participants

PRIMARY outcome

Timeframe: Up to six weeks

Population: Mild to Moderate Alzheimer's Disease patients

Changes in the amyloid load observed via PET imaging will be evaluated by comparing PET data acquired before and after the 10 tACS sessions. The metric used is SUVR, a measure of the amount of proteins in the brain identified at the PET exam. We will calculate the difference between pre and post tACS SUVR (dSUVR) for the entire brain and report the average value (and standard deviation) for the entire group of patients. A negative value express a decrease in the amount of proteins in the brain post tACS intervention. It must be considered that dSUVR values refer to the entire brain, however patients were treated according to personalized tACS montages targeting patient-specific regions mostly affected by the pathology. This might have led to slightly different changes in SUVR in different part of the brain across participants. Also, as per standard procedures, results are presented at group level, i.e. without considering individual differences in longitudinal amyloid load changes.

Outcome measures

Outcome measures
Measure
tACS
n=10 Participants
Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 10 sessions on consecutive weekdays. The tACS intervention (10 sessions) will be preceded and followed by amyloid PET imaging as well as a clinical/cognitive evaluation. The assessment of adverse effects will constitute a Primary outcome measure. Changes in amyloid load in the stimulated brain region will be evaluated and constitute a secondary outcome of the study. Clinically relevant changes in cognitive and clinical scores will be also evaluated as secondary outcomes. Stimulation will be also preceded and followed by electroencephalography (EEG) recording aimed at assessing changes in spectral power in the gamma band. tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
Change in Amyloid Burden
-1.55 dSUVR
Standard Deviation 0.9

SECONDARY outcome

Timeframe: Up to six weeks

Population: The assessment of the effect of 40 Hz tACS on EEG gamma-band spectral power.

EEG power spectral densities (PSD) before and after the tACS intervention were evaluated, specifically absolute and relative power density values (μV2/Hz) were calculated within the gamma band (35-45Hz). Changes in the spectral power are reported in term of percentage of changes in relative spectral power from Pre to Post tACS intervention.

Outcome measures

Outcome measures
Measure
tACS
n=10 Participants
Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 10 sessions on consecutive weekdays. The tACS intervention (10 sessions) will be preceded and followed by amyloid PET imaging as well as a clinical/cognitive evaluation. The assessment of adverse effects will constitute a Primary outcome measure. Changes in amyloid load in the stimulated brain region will be evaluated and constitute a secondary outcome of the study. Clinically relevant changes in cognitive and clinical scores will be also evaluated as secondary outcomes. Stimulation will be also preceded and followed by electroencephalography (EEG) recording aimed at assessing changes in spectral power in the gamma band. tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
Change in EEG Gamma-band Spectral Power
23.5 % difference in spectral power (μV2/Hz)
Standard Deviation 13.4

SECONDARY outcome

Timeframe: Up to six weeks

Change in Adas-Cog score will be reported, to document a potential clinical benefit of tACS. The scale ranges from a total score of 0-70 with higher score indicating greater cognitive impairment.

Outcome measures

Outcome measures
Measure
tACS
n=10 Participants
Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 10 sessions on consecutive weekdays. The tACS intervention (10 sessions) will be preceded and followed by amyloid PET imaging as well as a clinical/cognitive evaluation. The assessment of adverse effects will constitute a Primary outcome measure. Changes in amyloid load in the stimulated brain region will be evaluated and constitute a secondary outcome of the study. Clinically relevant changes in cognitive and clinical scores will be also evaluated as secondary outcomes. Stimulation will be also preceded and followed by electroencephalography (EEG) recording aimed at assessing changes in spectral power in the gamma band. tACS will be applied at a frequency of 40Hz and targeting the area of maximal tracer uptake on amyloid PET imaging using an individualized multielectrode design to maximize the induced electrical current to the target region.
Change in Adas-Cog Score
-0.97 Scores on a scale
Standard Deviation 3.88

Adverse Events

tACS

Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
tACS
n=10 participants at risk
Transcranial alternating current stimulation (tACS) tuned at the frequency of 40Hz (gamma frequency) will be applied for 1 hour in 10 sessions on consecutive weekdays.
General disorders
Headache
20.0%
2/10 • 5 months
General disorders
Scalp Pain
20.0%
2/10 • 5 months
General disorders
Neck Pain
20.0%
2/10 • 5 months
General disorders
Skin Irritation
50.0%
5/10 • 5 months
General disorders
Sensations under electrodes
80.0%
8/10 • 5 months
General disorders
Visual Changes
60.0%
6/10 • 5 months
General disorders
Nervousness
30.0%
3/10 • 5 months
General disorders
Difficulty concentrating
20.0%
2/10 • 5 months
General disorders
Hand tingling
10.0%
1/10 • 5 months
General disorders
Eye pain
10.0%
1/10 • 5 months

Additional Information

Principal Investigator - Emiliano Santarnecchi

BIDMC

Phone: 617-667-0326

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place