Alzheimer Disease, Late OnsetNCT04263194
Network-based rTMS in Alzheimer's Disease
A study testing rTMS in people with Alzheimer Disease, Late Onset and Alzheimer Disease, run by IRCCS Centro San Giovanni di Dio Fatebenefratelli at 1 site in Italy.
Trial summary
Severe alterations of brain networks connectivity have been described in Alzheimer's disease (AD). Repetitive Transcranial Magnetic Stimulation (rTMS) has gained evidence as an effective tool to modulate brain networks connectivity, leading to a recovery or reorganization of both local and remote brain regions… Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Alzheimer Disease, Late Onset, Alzheimer Disease, Cognitive Deterioration
- What is being tested?
- rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteItaly
- Study dates
- 21 Mar 2019to 21 Mar 2024
- 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 55 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Mini-Mental State Examination score >=16, <=24
- Anti-cholinesterase treatment for at least 3 months prior the start date
Who cannot join
- Enrollment in other clinical and pharmacological trials
- Previous evidence of any other CNS disorder (e.g. epilepsy, infectious diseases, frontotemporal, Parkinson or Pick's disease)
- History of major psychiatric disorders
- History of alchol or substance abuse
- Stress-related skin problems
- Current consumption of psychiatric medication
- Presence of metal implants or any implanted electronics
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
IRCCS Centro San Giovanni di Dio Fatebenefratelli
Brescia, Lombardy, 25125
Debora Brignani
About this study
Official title: Novel Tailored Network-based rTMS Treatments in Alzheimer's Disease: an Integrated Multiimaging Approach
Severe alterations of brain networks connectivity have been described in Alzheimer's disease (AD). Repetitive Transcranial Magnetic Stimulation (rTMS) has gained evidence as an effective tool to modulate brain networks connectivity, leading to a recovery or reorganization of both local and remote brain regions functionally connected to the stimulated area. The investogators propose an innovative tailored network-based rTMS treatment to ameliorate cognitive symptoms in mild AD, through the boosting of connectivity within brain networks affected by AD pathophysiology. The combination of the proposed intervention with an integrated multi-modal imaging approach will allow to evaluate the neural mechanisms underlying the clinical response to the treatment and to define quantitative markers of clinical impact on AD. If successful, the present proposal would immediately impact on patient's quality of life, with important implications for the time and costs of delivery of rehabilitative services.
Read the detailed description
Currently, no effective cure is available for Alzheimer's disease (AD). Repetitive Transcranial Magnetic Stimulation (rTMS) has gained increasing attention as a potential treatment for various neurological and psychiatric disorders, but available rTMS studies are flawed by inaccurate anatomical targeting, inadequate sample size, unsatisfactory controls and lacking blindness. To date, the elective target area of rTMS interventions in AD has been the dorsolateral prefrontal cortex (DLPFC), a core area of the Central Executive network (CEN), which plays a key role in regulating executive functions, attention and working memory. While the CEN has recently been described as dysfunctional in AD, AD pathophysiology has been mainly associated with the breakdown of the Default Mode network (DMN) and with structural disconnection of its parietal nodes. The DMN plays a crucial role in episodic memory retrieval and incorporates various brain regions, among which parietal areas are highly connected with the rest of the brain. The present multicenter, double-blind, randomized and placebo-controlled study has the ambition to provide evidence of the efficacy of two tailored network-based rTMS treatments in mild AD, through the enhancement of connectivity of CEN and DMN. Innovative integrated multi-modal imaging investigations will further enrich this proposal allowing to identify quantifiable markers underlying the clinical impact of rTMS on AD.
- Being tested
- rTMS, Sham rTMS
- Keywords
- TMS, rTMS, Alzheimer Disease
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMSDevice
25 min of high frequency (20 Hz) repetitive TMS applied at 100% of resting motor threshold (rMT).
Sham rTMSDevice
Placebo intervention will consist in the same procedure but using a sham rTMS coil.
| Study group | Role | What they receive |
|---|---|---|
| Default Mode Network (DMN) | Experimental | The treatment will consist in the individually tailored stimulation of a DMN node (i.e. left inferior parietal lobe). Receives: Device: rTMS |
| Central Executive Network (CEN) | Experimental | The treatment will consist in the individually tailored stimulation of a CEN node (i.e. left dorsolateral prefrontal cortex). Receives: Device: rTMS |
| Placebo | Placebo comparator | The treatment will consist in targeting the upper part of the scalp (i.e. CZ) while using a sham rTMS coil. Receives: Device: Sham rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ADAS-Cog scale scores
A brief neuropsychological assessment used to assess the severity of cognitive symptoms of dementia
Measured: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Secondary outcomes (4)
Change in CANTAB battery scores
The scores on two tests of CANTAB battery (www.cambridgecognition.com):
- Change in Associative Learning test (PAL)
- Change in Spatial Working Memory test (SWM)
Measured: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Change in brain connectivity
TMS-evoked cortical responses (TEPs) will serve as markers of reactivity of the stimulated area as well as markers of the connectivity between targeted cortex and functionally connected areas underlying DMN or CEN.
Measured: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Change in brain plasticity
A theta burst stimulation (TBS) protocol will be used to probe plasticity changes
Measured: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Change in MRI measures of functional and structural connectivity
Measured: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2020
- Study start21 Mar 2019
- Primary completion21 Sep 2023 (estimated)
- Study completion21 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer Disease, Late OnsetStudies 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
- Parallel groups
- Model description
- After recruitment, patients will be randomized and assigned to one of three rTMS treatments: DMN (N=20), CEN (N=20) or placebo (N=20). The rTMS treatment will consist of 2 phases: an intensive phase and a maintenance phase. The intensive phase will involve 3 weeks of treatment, 5 days per week (15 sessions in total). The maintenance will consist of 1 session of treatment every 2 weeks for 5 months (10 sessions in total). Overall, the patients will undergo 25 sessions of rTMS delivered over 6 months. At baseline (T0), at the end of the intensive phase (T1) and at the end of the maintenance phase (T2) all patients will undergo a clinical and cognitive assessment and a multi-modal imaging data collection.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Centro San Giovanni di Dio Fatebenefratelli
- Sponsor type
- University, hospital or other
- Collaborators
- I.R.C.C.S. Fondazione Santa Lucia, Ministero della Salute, Italy
- Responsible party
- Principal investigator, Debora Brignani, IRCCS Centro San Giovanni di Dio Fatebenefratelli
- Investigators
- Debora Brignani, Principal investigator, IRCCS Centro San Giovanni di Dio Fatebenefratelli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04263194
- Sponsor's protocol ID
- GR-2016-02364718
- Status last verified
- Mar 2023
- First submitted
- 30 Jan 2020
- Last updated
- 13 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Tailored Network-based rTMS Treatments in Alzheimer's Disease: an Integrated Multiimaging Approach
- ClinicalTrials.gov ID
- NCT04263194
- Acronym / sponsor ID
- GR-2016-02364718
- Keywords
- TMS, rTMS, Alzheimer Disease
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- IRCCS Centro San Giovanni di Dio FatebenefratelliUniversity, hospital or other
- Collaborators
- I.R.C.C.S. Fondazione Santa Lucia, Ministero della Salute, Italy
- Study start
- 21 Mar 2019 (actual)
- Primary completion
- 21 Sep 2023 (estimated)
- Study completion
- 21 Mar 2024 (estimated)
- First posted
- 10 Feb 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.
Severe alterations of brain networks connectivity have been described in Alzheimer's disease (AD). Repetitive Transcranial Magnetic Stimulation (rTMS) has gained evidence as an effective tool to modulate brain networks connectivity, leading to a recovery or reorganization of both local and remote brain regions functionally connected to the stimulated area. The investogators propose an innovative tailored network-based rTMS treatment to ameliorate cognitive symptoms in mild AD, through the boosting of connectivity within brain networks affected by AD pathophysiology. The combination of the proposed intervention with an integrated multi-modal imaging approach will allow to evaluate the neural mechanisms underlying the clinical response to the treatment and to define quantitative markers of clinical impact on AD. If successful, the present proposal would immediately impact on patient's quality of life, with important implications for the time and costs of delivery of rehabilitative services.
Detailed description
Currently, no effective cure is available for Alzheimer's disease (AD). Repetitive Transcranial Magnetic Stimulation (rTMS) has gained increasing attention as a potential treatment for various neurological and psychiatric disorders, but available rTMS studies are flawed by inaccurate anatomical targeting, inadequate sample size, unsatisfactory controls and lacking blindness. To date, the elective target area of rTMS interventions in AD has been the dorsolateral prefrontal cortex (DLPFC), a core area of the Central Executive network (CEN), which plays a key role in regulating executive functions, attention and working memory. While the CEN has recently been described as dysfunctional in AD, AD pathophysiology has been mainly associated with the breakdown of the Default Mode network (DMN) and with structural disconnection of its parietal nodes. The DMN plays a crucial role in episodic memory retrieval and incorporates various brain regions, among which parietal areas are highly connected with the rest of the brain. The present multicenter, double-blind, randomized and placebo-controlled study has the ambition to provide evidence of the efficacy of two tailored network-based rTMS treatments in mild AD, through the enhancement of connectivity of CEN and DMN. Innovative integrated multi-modal imaging investigations will further enrich this proposal allowing to identify quantifiable markers underlying the clinical impact of rTMS on AD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
- Model description
- After recruitment, patients will be randomized and assigned to one of three rTMS treatments: DMN (N=20), CEN (N=20) or placebo (N=20). The rTMS treatment will consist of 2 phases: an intensive phase and a maintenance phase. The intensive phase will involve 3 weeks of treatment, 5 days per week (15 sessions in total). The maintenance will consist of 1 session of treatment every 2 weeks for 5 months (10 sessions in total). Overall, the patients will undergo 25 sessions of rTMS delivered over 6 months. At baseline (T0), at the end of the intensive phase (T1) and at the end of the maintenance phase (T2) all patients will undergo a clinical and cognitive assessment and a multi-modal imaging data collection.
| Arm | Type | Receives |
|---|---|---|
| Default Mode Network (DMN) | Experimental | Device: rTMSThe treatment will consist in the individually tailored stimulation of a DMN node (i.e. left inferior parietal lobe). |
| Central Executive Network (CEN) | Experimental | Device: rTMSThe treatment will consist in the individually tailored stimulation of a CEN node (i.e. left dorsolateral prefrontal cortex). |
| Placebo | Placebo comparator | Device: Sham rTMSThe treatment will consist in targeting the upper part of the scalp (i.e. CZ) while using a sham rTMS coil. |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Mini-Mental State Examination score >=16, <=24
- Anti-cholinesterase treatment for at least 3 months prior the start date
Key exclusion criteria (7 listed)
- Enrollment in other clinical and pharmacological trials
- Previous evidence of any other CNS disorder (e.g. epilepsy, infectious diseases, frontotemporal, Parkinson or Pick's disease)
- History of major psychiatric disorders
- History of alchol or substance abuse
- Stress-related skin problems
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 |
|---|---|---|
| rTMS25 min of high frequency (20 Hz) repetitive TMS applied at 100% of resting motor threshold (rMT). | Device | Central Executive Network (CEN), Default Mode Network (DMN) |
| Sham rTMSPlacebo intervention will consist in the same procedure but using a sham rTMS coil. | Device | Placebo |
Primary outcome
Change in ADAS-Cog scale scores
Time frame: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
A brief neuropsychological assessment used to assess the severity of cognitive symptoms of dementia
4 secondary outcomes
Change in CANTAB battery scores
Time frame: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Change in brain connectivity
Time frame: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Change in brain plasticity
Time frame: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Change in MRI measures of functional and structural connectivity
Time frame: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2023.
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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.
Debora Brignani principal investigator
IRCCS Centro San Giovanni di Dio Fatebenefratelli
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rTMS in people with Alzheimer Disease, Late Onset and Alzheimer Disease, run by IRCCS Centro San Giovanni di Dio Fatebenefratelli 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 2 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 13 Mar 2023. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Debora Brignani (0303501597, dbrignani@fatebenefratelli.eu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in ADAS-Cog scale scores (time frame: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Mar 2023.