Modulators of Gamma tACS in Alzheimer's Disease (Mod-GammAD) (Mod-GammAD)

November 17, 2022 updated by: Barbara Borroni, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Interventional Cross-over Study to Evaluate the Modulators of Efficacy of Alternating Current Brain Stimulation (tACS) in Patients With Alzheimer's Disease

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 the modulators of response on cognitive measure to a single stimulation with gamma tACS on the posterior parietal cortex in patients with Mild Cognitive Impairment due to Alzheimer's disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 the modulators of response on cognitive measure to a single stimulation with gamma tACS on the posterior parietal cortex 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. Modulators of response, including cognitive reserve, baseline impairment, apo-E genotype, MRI measures of atrophy and connectivity, electric field modelling, will be considered.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • BS
      • Brescia, BS, Italy, 25100
        • AO Spedali Civili

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 AD
  • History of seizures
  • Pregnancy
  • Metal implants in the head (except dental fillings)
  • Electronic implants (i.e. pace-maker, implanted medical pump)
  • Age <18 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: real tACS
Single session of gamma tACS (40 Hz) at 3 mA over the superior parietal cortex (Precuneus)
Device: Gamma tACS (40 Hz) over the superior parietal cortex
Single session of gamma tACS (40 Hz) over the superior parietal cortex
Sham Comparator: sham tACS
Single session of sham tACS over the superior parietal cortex (Precuneus)
Device: Sham tACS over the superior parietal cortex
Single session of sham tACS over the superior parietal cortex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Rey Auditory Verbal Learning Test scores
Time Frame: Baseline (immediately before the intervention) - Immediately after the intervention

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).
Baseline (immediately before the intervention) - Immediately after the intervention
Changes in Face-Name Associative Memory Test scores
Time Frame: During the intervention compared to sham comparator

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).
During the intervention compared to sham comparator

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in SAI measurements
Time Frame: Baseline (immediately before the intervention) - Immediately after the intervention
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.
Baseline (immediately before the intervention) - Immediately after the intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 10, 2021

Primary Completion (Actual)

April 30, 2021

Study Completion (Actual)

April 30, 2021

Study Registration Dates

First Submitted

March 10, 2021

First Submitted That Met QC Criteria

April 8, 2021

First Posted (Actual)

April 13, 2021

Study Record Updates

Last Update Posted (Actual)

November 21, 2022

Last Update Submitted That Met QC Criteria

November 17, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NP4479

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD 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

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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