Alzheimer DiseaseGammADNCT04515433
Gamma tACS in Alzheimer's Disease
A study testing Gamma tACS (40 Hz) over the superior parietal cortex in people with Alzheimer Disease, run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Gamma tACS (40 Hz) over the superior parietal cortex
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 20 Aug 2020to 30 Sep 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Mild Cognitive Impairment due to Alzheimer's disease (according to Albert et al., Alzheimers Dement 2011).
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Alzheimer Disease
- Being tested
- Gamma tACS (40 Hz) over the superior parietal cortex
- Keywords
- Alzheimer's disease, transcranial Alternating Current Stimulation, tACS, Gamma stimulation
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gamma tACS (40 Hz) over the superior parietal cortexDevice
Single session of gamma tACS (40 Hz) over the superior parietal cortex
| Study group | Role | What they receive |
|---|---|---|
| real tACS | Experimental | Single session of gamma tACS (40 Hz) at 3 mA over the superior parietal cortex (Precuneus) Receives: Device: Gamma tACS (40 Hz) over the superior parietal cortex |
| sham tACS | Placebo comparator | Single session of sham tACS over the superior parietal cortex (Precuneus) Receives: Device: Gamma tACS (40 Hz) over the superior parietal cortex |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline (immediately before the intervention) - Immediately after the intervention
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).
Measured: During the intervention
Secondary outcomes (1)
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.
Measured: Baseline (immediately before the intervention) - Immediately after the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2020
- Study start20 Aug 2020
- Primary completion30 Sep 2020
- Study completion30 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Barbara Borroni, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Investigators
- Barbara Borroni, MD, Principal investigator, Azienda Ospedaliera Spedali Civili, BresciaAlberto Benussi, MD, Principal investigator, Azienda Ospedaliera Spedali Civili, Brescia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04515433
- Sponsor's protocol ID
- NP3847
- Acronym
- GammAD
- Status last verified
- Mar 2021
- First submitted
- 11 Aug 2020
- Last updated
- 19 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All data, including outcome measure results, study protocol and statistical analysis plan, will be shared upon reasonable request.
Publications
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.
PubMed 19400723Iaccarino 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.
PubMed 27929004Adaikkan 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.
PubMed 31076275Martorell 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.
PubMed 30879788Herrmann 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.
PubMed 23785325
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04515433
- Acronym / sponsor ID
- GammAD / NP3847
- Conditions
- Alzheimer Disease
- Keywords
- Alzheimer's disease, transcranial Alternating Current Stimulation, tACS, Gamma stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di BresciaUniversity, hospital or other
- Study start
- 20 Aug 2020 (actual)
- Primary completion
- 30 Sep 2020 (actual)
- Study completion
- 30 Sep 2020 (actual)
- First posted
- 17 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| real tACS | Experimental | Device: Gamma tACS (40 Hz) over the superior parietal cortexSingle session of gamma tACS (40 Hz) at 3 mA over the superior parietal cortex (Precuneus) |
| sham tACS | Placebo comparator | Device: Gamma tACS (40 Hz) over the superior parietal cortexSingle session of sham tACS over the superior parietal cortex (Precuneus) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Mild Cognitive Impairment due to Alzheimer's disease (according to Albert et al., Alzheimers Dement 2011).
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gamma tACS (40 Hz) over the superior parietal cortexSingle session of gamma tACS (40 Hz) over the superior parietal cortex | Device | real tACS, sham tACS |
Primary outcome
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).
Changes in Face-Name Associative Memory Test scores
Time frame: During the intervention
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).
1 secondary outcome
Change in SAI measurements
Time frame: Baseline (immediately before the intervention) - Immediately after the intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2021.
- Background: PubMed 19400723Fries 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.
- Background: PubMed 27929004Iaccarino 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.
- Background: PubMed 31076275Adaikkan 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.
- Background: PubMed 30879788Martorell 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.
- Background: PubMed 23785325Herrmann 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.
- Individual participant dataSharing planned: Yes. All data, including outcome measure results, study protocol and statistical analysis plan, will be shared upon reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barbara Borroni, MD principal investigator
Azienda Ospedaliera Spedali Civili, Brescia
Alberto Benussi, MD principal investigator
Azienda Ospedaliera Spedali Civili, Brescia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Gamma tACS (40 Hz) over the superior parietal cortex in people with Alzheimer Disease, run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Rey Auditory Verbal Learning Test scores (time frame: Baseline (immediately before the intervention) - Immediately after the intervention). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04515433, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2021.