The main objective is to replicate the results of the recent successful efficacy study on precuneus rTMS in AD by Koch et al. (2022). Secondary objectives include investigating what functional brain activity/network changes underlie the effects of…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
neurodegeneratieve aandoeningen, dementie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome will be the pre-to-post difference in clinical dementia
rating, as measured with the clinical dementia rating - sum of boxes scale
(CDR-SB), in the real rTMS condition compared to the sham condition.
Secondary outcome
Secondary outcome measures include additional cognitive and clinical rating
scales, neuropsychological assessment batteries, magnetoencephalography, and
cerebrospinal fluid biomarkers.
Background summary
New amyloid-targeting drugs for Alzheimer's disease (AD) offer minimal or
unclear efficacy and often cause adverse events, highlighting the need for new
therapies. In recent years, repetitive transcranial magnetic stimulation (rTMS)
has shown increasing success. A recent randomized, double-blind,
sham-controlled, phase 2 trial by Koch et al. (2022) {Koch, 2022 #10}
demonstrated promising results from a 24-week rTMS treatment protocol targeting
the precuneus. This brain region is considered a main hub of the human brain
connectome and a prominent area of AD pathology. The results showed stable
cognitive performance and increased brain activity in the treatment group,
whereas the sham group worsened. We aim to conduct a replication study and
further investigate the working mechanism of precuneus-rTMS in AD to gain a
better understanding.
Study objective
The main objective is to replicate the results of the recent successful
efficacy study on precuneus rTMS in AD by Koch et al. (2022). Secondary
objectives include investigating what functional brain activity/network changes
underlie the effects of rTMS and whether differences in cognitive performance
are reflected in cerebrospinal fluid AD biomarker levels.
Study design
A monocentric, 2-arm, randomized, double-blind, sham-controlled, phase 2 trial
over 24 weeks with a 6-month follow-up to confirm the effectiveness of
precuneus rTMS in individuals with mild AD.
Intervention
32 sessions of 20 Hz rTMS over the precuneus: a 2-week intensive phase with
daily (5x/week) rTMS, followed by a 22-week maintenance phase with weekly rTMS.
Study burden and risks
rTMS is a form of non-invasive brain stimulation and is proven to be safe and
generally tolerable, with sometimes mild side effects including transient
headache and scalp sensations. The risk of inducing an epileptic seizure
remains negligible. The main burden for both groups is the number of hospital
visits due to the extensive treatment protocol of 32 sessions. Benefits for the
treatment group include a possible temporary improvement and/or stabilizing
effect on cognitive decline. By participating, both groups help the field gain
knowledge about AD and potential new treatment options.
De Boelelaan 1118
Amsterdam 1081HZ
NL
De Boelelaan 1118
Amsterdam 1081HZ
NL
Listed location countries
Age
Inclusion criteria
- Biomarker-supported Alzheimer*s disease (Abnormal CSF p-tau/Aβ42 ratio of >
0.023 or Amyloid PET positive).
- Between 50 and 85 years old.
- Clinical dementia rating (CDR) score of 0.5 or 1 {Morris, 1993 #80}.
- Mini-mental state examination (MMSE) score between 18 and 26.
- Presence of a caregiver.
Exclusion criteria
- Medical history of other neurodegenerative diseases, stroke, or epilepsy.
- Severe psychiatric dysregulation, hampering successful study participation
and leading to possible cognitive impairment. Eligibility for participation
will be based on clinical evaluation by an expert neurologist and/or
psychiatrist.
- Extensive cerebrovascular damage on MRI classified as Fazekas level 2 or 3.
Patients with abnormalities classified as Fazekas level 3 are excluded {Fazekas
F Fau - Chawluk, #115}. For Fazekas level 2, patient*s eligibility for
participation will be evaluated by an expert neurologist.
- Presence of metal in the head or cranial/thoracic implants, including
cochlear implants.
- Cholinesterase inhibitors with unstable d osage in the last 2 months.
- Extreme claustrophobia or metallic objects in or on the body, preventing MRI
and MEG examination.
- Previous rTMS treatment (for blinding reasons).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL87473.018.24 |