Network-based rTMS in Alzheimer's Disease

Alzheimer Disease Clinical Trial

Official title:

Novel Tailored Network-based rTMS Treatments in Alzheimer's Disease: an Integrated Multiimaging Approach

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04263194
• Other study ID #: GR-2016-02364718
• Status: Recruiting
• Phase: N/A
• Start date: March 21, 2019
• Est. completion date: March 21, 2024

Study information

• Verified date: March 2023
• Source: IRCCS Centro San Giovanni di Dio Fatebenefratelli
• Contact: Debora Brignani
• Phone: 0303501597
• Email: dbrignani[@]fatebenefratelli.eu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: March 21, 2024
• Est. primary completion date: September 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

Inclusion Criteria:

• Mini-Mental State Examination score >=16, <=24

• Anti-cholinesterase treatment for at least 3 months prior the start date

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer Disease, Late Onset
• Cognitive Deterioration

Intervention

Device:
• rTMS
25 min of high frequency (20 Hz) repetitive TMS applied at 100% of resting motor threshold (rMT).
• Sham rTMS
Placebo intervention will consist in the same procedure but using a sham rTMS coil.

Locations

Country	Name	City	State
Italy	IRCCS Centro San Giovanni di Dio Fatebenefratelli	Brescia	Lombardia

Sponsors (3)

Lead Sponsor	Collaborator
IRCCS Centro San Giovanni di Dio Fatebenefratelli	I.R.C.C.S. Fondazione Santa Lucia, Ministero della Salute, Italy

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in ADAS-Cog scale scores	A brief neuropsychological assessment used to assess the severity of cognitive symptoms of dementia	At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Secondary	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)	At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Secondary	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.	At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Secondary	Change in brain plasticity	A theta burst stimulation (TBS) protocol will be used to probe plasticity changes	At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Secondary	Change in MRI measures of functional and structural connectivity		At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)