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Gamma tACS in Alzheimer's Disease (GammAD)

Primary Purpose

Alzheimer Disease

Status
Completed
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Gamma tACS (40 Hz) over the superior parietal cortex
Sponsored by
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease focused on measuring Alzheimer's disease, transcranial Alternating Current Stimulation, tACS, Gamma stimulation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

- Mild Cognitive Impairment due to Alzheimer's disease (according to Albert et al., Alzheimers Dement 2011).

Exclusion Criteria:

  • Cerebrovascular disorders, previous stroke, hydrocephalus, and intra-cranial mass documented by MRI.
  • History of traumatic brain injury or other neurological diseases.
  • Serious medical illness other than FTD
  • History of seizures
  • Pregnancy
  • Metal implants in the head (except dental fillings)
  • Electronic implants (i.e. pace-maker, implanted medical pump)
  • Age <18 years

Sites / Locations

  • AO Spedali Civili

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

real tACS

sham tACS

Arm Description

Single session of gamma tACS (40 Hz) at 3 mA over the superior parietal cortex (Precuneus)

Single session of sham tACS over the superior parietal cortex (Precuneus)

Outcomes

Primary Outcome Measures

Changes in Rey Auditory Verbal Learning Test scores
Participants are given a list of 15 unrelated words repeated over five different trials and are asked to repeat. Another list of 15 unrelated words are given and the patient must again repeat the original list of 15 words and then again after 30 minutes. The score ranges from 0 (worse performance) to 15 (best performance).
Changes in Face-Name Associative Memory Test scores
The Face-Name Associative Memory Test is a cross-modal associative memory test, it includes 20 face-name pairs. The administration procedure starts with the presentation of 20 faces with each name and participants should read the name underneath the faces and try to learn each face-name pair. After 5 minutes, the faces are shown one by one and participants are asked to recall the associated names from 4 different names. The correct number of pairs recalled is recorded. The score ranges from 0 (worse performance) to 20 (best performance).

Secondary Outcome Measures

Change in SAI measurements
By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of gamma tACS on short latency afferent inhibition (SAI), which is a marker of cholinergic transmission.

Full Information

First Posted
August 11, 2020
Last Updated
March 17, 2021
Sponsor
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
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1. Study Identification

Unique Protocol Identification Number
NCT04515433
Brief Title
Gamma tACS in Alzheimer's Disease
Acronym
GammAD
Official Title
Interventional Cross-over Study to Evaluate the Efficacy on Cognitive Performance of Alternating Current Brain Stimulation (tACS) in Patients Suffering From Neurodegenerative Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
August 20, 2020 (Actual)
Primary Completion Date
September 30, 2020 (Actual)
Study Completion Date
September 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Brain oscillations are ubiquitous in the human brain and have been implicated in cognitive and behavioral states defined in precisely tuned neural networks. In neurodegenerative disorders, neurodegeneration is accompanied by changes in oscillatory activity leading to the emerging concept of neurological and psychiatric disorders as "oscillopathies". Alzheimer's disease, which accounts for the vast majority of age-related dementias, is characterised by a prominent disruption of oscillations in the gamma frequency band. The restoration of gamma oscillations by neural entrainment in animal models of Alzheimer's disease have shown a remarkable decrease in the pathological burden of amyloid and tau via increased microglial activity, resulting in a significant increase of cognitive performances. Transcranial alternating current brain stimulation (tACS), is a neurophysiological method of non-invasive modulation of the excitability of the central nervous system that is having an increasingly numerous spectrum of potential therapeutic applications. Recent studies have demonstrated the effectiveness of this method in modulating the natural frequencies of cerebral oscillation, underlying multiple cognitive processes such as verbal memory, perception and working memory. On the basis of these premises, the treatment with gamma tACS is proposed in patients affected by Alzheimer's disease. In this randomized, double-blind, sham-controlled, cross-over study, the investigators will evaluate whether a single stimulation with gamma tACS on the posterior parietal cortex can improve symptoms in patients with Mild Cognitive Impairment due to Alzheimer's disease.
Detailed Description
Brain oscillations are ubiquitous in the human brain and have been implicated in cognitive and behavioral states defined in precisely tuned neural networks. In neurodegenerative disorders, neurodegeneration is accompanied by changes in oscillatory activity leading to the emerging concept of neurological and psychiatric disorders as "oscillopathies". Alzheimer's disease, which accounts for the vast majority of age-related dementias, is characterised by a prominent disruption of oscillations in the gamma frequency band. The restoration of gamma oscillations by neural entrainment in animal models of Alzheimer's disease have shown a remarkable decrease in the pathological burden of amyloid and tau via increased microglial activity, resulting in a significant increase of cognitive performances. Transcranial alternating current brain stimulation (tACS), is a neurophysiological method of non-invasive modulation of the excitability of the central nervous system that is having an increasingly numerous spectrum of potential therapeutic applications. Recent studies have demonstrated the effectiveness of this method in modulating the natural frequencies of cerebral oscillation, underlying multiple cognitive processes such as verbal memory, perception and working memory. On the basis of these premises, the treatment with gamma tACS is proposed in patients affected by Alzheimer's disease. In this randomized, double-blind, sham-controlled, cross-over study, the investigators will evaluate whether a single stimulation with gamma tACS on the posterior parietal cortex can improve symptoms in patients with Mild Cognitive Impairment due to Alzheimer's disease. Subjects will be randomized in two groups, one receiving a single treatment with gamma tACS (40 Hz) first and the other receiving sham stimulation. After one week the treatments will be exchanged. Patients will be evaluated with neuropsychological tests and neurophysiological measures of cholinergic transmission.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
Keywords
Alzheimer's disease, transcranial Alternating Current Stimulation, tACS, Gamma stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
real tACS
Arm Type
Experimental
Arm Description
Single session of gamma tACS (40 Hz) at 3 mA over the superior parietal cortex (Precuneus)
Arm Title
sham tACS
Arm Type
Placebo Comparator
Arm Description
Single session of sham tACS over the superior parietal cortex (Precuneus)
Intervention Type
Device
Intervention Name(s)
Gamma tACS (40 Hz) over the superior parietal cortex
Intervention Description
Single session of gamma tACS (40 Hz) over the superior parietal cortex
Primary Outcome Measure Information:
Title
Changes in Rey Auditory Verbal Learning Test scores
Description
Participants are given a list of 15 unrelated words repeated over five different trials and are asked to repeat. Another list of 15 unrelated words are given and the patient must again repeat the original list of 15 words and then again after 30 minutes. The score ranges from 0 (worse performance) to 15 (best performance).
Time Frame
Baseline (immediately before the intervention) - Immediately after the intervention
Title
Changes in Face-Name Associative Memory Test scores
Description
The Face-Name Associative Memory Test is a cross-modal associative memory test, it includes 20 face-name pairs. The administration procedure starts with the presentation of 20 faces with each name and participants should read the name underneath the faces and try to learn each face-name pair. After 5 minutes, the faces are shown one by one and participants are asked to recall the associated names from 4 different names. The correct number of pairs recalled is recorded. The score ranges from 0 (worse performance) to 20 (best performance).
Time Frame
During the intervention
Secondary Outcome Measure Information:
Title
Change in SAI measurements
Description
By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of gamma tACS on short latency afferent inhibition (SAI), which is a marker of cholinergic transmission.
Time Frame
Baseline (immediately before the intervention) - Immediately after the intervention

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - Mild Cognitive Impairment due to Alzheimer's disease (according to Albert et al., Alzheimers Dement 2011). Exclusion Criteria: Cerebrovascular disorders, previous stroke, hydrocephalus, and intra-cranial mass documented by MRI. History of traumatic brain injury or other neurological diseases. Serious medical illness other than FTD History of seizures Pregnancy Metal implants in the head (except dental fillings) Electronic implants (i.e. pace-maker, implanted medical pump) Age <18 years
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barbara Borroni, MD
Organizational Affiliation
Azienda Ospedaliera Spedali Civili, Brescia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alberto Benussi, MD
Organizational Affiliation
Azienda Ospedaliera Spedali Civili, Brescia
Official's Role
Principal Investigator
Facility Information:
Facility Name
AO Spedali Civili
City
Brescia
State/Province
BS
ZIP/Postal Code
25100
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All data, including outcome measure results, study protocol and statistical analysis plan, will be shared upon reasonable request.
IPD Sharing Time Frame
Data will be shared after the study completion indefinitely.
IPD Sharing Access Criteria
Reasonable request
Citations:
PubMed Identifier
19400723
Citation
Fries P. Neuronal gamma-band synchronization as a fundamental process in cortical computation. Annu Rev Neurosci. 2009;32:209-24. doi: 10.1146/annurev.neuro.051508.135603.
Results Reference
background
PubMed Identifier
27929004
Citation
Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, Adaikkan C, Canter RG, Rueda R, Brown EN, Boyden ES, Tsai LH. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 2016 Dec 7;540(7632):230-235. doi: 10.1038/nature20587. Erratum In: Nature. 2018 Oct;562(7725):E1.
Results Reference
background
PubMed Identifier
31076275
Citation
Adaikkan C, Middleton SJ, Marco A, Pao PC, Mathys H, Kim DN, Gao F, Young JZ, Suk HJ, Boyden ES, McHugh TJ, Tsai LH. Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection. Neuron. 2019 Jun 5;102(5):929-943.e8. doi: 10.1016/j.neuron.2019.04.011. Epub 2019 May 7.
Results Reference
background
PubMed Identifier
30879788
Citation
Martorell AJ, Paulson AL, Suk HJ, Abdurrob F, Drummond GT, Guan W, Young JZ, Kim DN, Kritskiy O, Barker SJ, Mangena V, Prince SM, Brown EN, Chung K, Boyden ES, Singer AC, Tsai LH. Multi-sensory Gamma Stimulation Ameliorates Alzheimer's-Associated Pathology and Improves Cognition. Cell. 2019 Apr 4;177(2):256-271.e22. doi: 10.1016/j.cell.2019.02.014. Epub 2019 Mar 14.
Results Reference
background
PubMed Identifier
23785325
Citation
Herrmann CS, Rach S, Neuling T, Struber D. Transcranial alternating current stimulation: a review of the underlying mechanisms and modulation of cognitive processes. Front Hum Neurosci. 2013 Jun 14;7:279. doi: 10.3389/fnhum.2013.00279. eCollection 2013.
Results Reference
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Gamma tACS in Alzheimer's Disease

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