Using deep rTMS to improve memory in Alzheimer's Disease

Protocol for Maintaining and Improving Mental Status in Alzheimer's Disease (PROMIS-AD): a Pilot Study of Repetitive Transcranial Magnetic Stimulation of the Precuneus for Alzheimer&Amp;Amp;#39;s Disease

This study is testing if a new brain treatment called deep rTMS can help improve memory in people with mild to moderate Alzheimer's Disease.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 60 Years to 100 Years
• Sex: All
• Sponsor: University of California, Los Angeles (other)
• Drugs / interventions: lecanemab, aducanumab, donanemab
• Locations: 1 site (Los Angeles, California)
• Trial ID: NCT06597942 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the feasibility and potential efficacy of deep repetitive transcranial magnetic stimulation (rTMS) targeting the precuneus in patients with mild to moderate Alzheimer's Disease. The study aims to determine if this non-invasive treatment can lead to positive brain changes and improve memory function. Participants will undergo memory testing, brain imaging, and bloodwork while receiving either active or placebo stimulation. The trial is designed to gather data on both short-term and long-term effects of rTMS on cognitive function in Alzheimer's patients.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 60-100 with a diagnosis of mild to moderate probable Alzheimer's Disease who can provide informed consent.

Not a fit: Patients with severe Alzheimer's Disease or those who are unable to participate in the study due to cognitive or behavioral issues may not benefit.

Why it matters

Potential benefit: If successful, this treatment could enhance memory function and potentially slow the progression of Alzheimer's Disease.

How similar studies have performed: Previous studies have shown mixed results with rTMS in Alzheimer's, but recent findings targeting the precuneus are promising.

Eligibility criteria

Inclusion Criteria:

* Age 60-100 at the start of the study
* Established diagnosis of Alzheimer's Clinical Syndrome (which is also met through a diagnosis of Alzheimer's Dementia)
* Agreement to participate in study and able to complete informed consent process
* Have a caregiver/study partner who can accompany them to all study visits
* Have a known alternate surrogate decision-maker (in case needed) who can accompany them to the informed consent visit (this person may be the study partner mentioned above)
* Screening MMSE score of 18-26
* Screening GDS score \<6
* Either 1) treated with memory-enhancing medication (cholinesterase inhibitor) for at least 2 months, 2) failed trial with no plan to re-trial, or 3) no trial planned during the course of the study for other reasons
* No change in use of psychotropic medication for the treatment of depression, anxiety, ADHD, or psychosis for 2 weeks prior to the study

Exclusion Criteria:

* Participant and/or their surrogate are unwilling or unable to provide informed consent
* Currently pregnant or potentially pregnant
* Diagnosis of a dementia or cognitive disorder due to a cause other than Alzheimer's Disease
* Diagnosis of severe Dementia (CDR \> 2.0) at the start of the study
* History of substance use disorder currently not in sustained remission
* Substance misuse within the past 6 months (excluding nicotine or caffeine)
* History of stroke, traumatic brain injury with loss of consciousness, or other major neurologic disorder (e.g., epilepsy, Huntington's disease, Parkinson's disease)
* History of seizure disorder or family history of seizure disorder in a first-degree relative
* Poorly-controlled hypertension, cardiovascular disease, or cerebrovascular disease
* History of any other major active medical, neurologic, or psychiatric illness affecting cognition (associated with cognitive impairment) or a participant's ability to safely and meaningfully participate in the study
* Non-fluent in English (not native or functionally-native)
* Contraindication to TMS or MRI including claustrophobia, MRI-incompatible or unknown metal in body (including facial tattoos with uknown or metallic inks), surgery within 60 days, certain implants (excluding dental fillings), or previous abnormal MRI results.
* Has previous history of TMS treatment in the past (not TMS naïve)
* Currently enrolled in a memory-enhancement study
* Alteration in cognitive-enhancement medication dose within the past 2 months or active plans for dose alteration during the course of the study (previously unplanned changes that occur during the study will be examined on a case-by-case basis)
* History of treatment with lecanemab, aducanumab, donanemab, or other monoclonal antibody treatment for Alzheimer's Disease (due to lack of knowledge surrounding the impacts of these treatments)
* Currently or within the past 2 weeks taking any of the following classes of medication:

  * Anticholinergic (e.g., tolterodine, benztropine)
  * Sedating antihistamines (e.g., diphenhydramine)
  * any drug that has significant anticholinergic or antihistaminic side effects (e.g., tricyclic antidepressant medications, mirtazapine).
  * Benzodiazepines. While not a strict rule out, this will be decided on a case-by-case basis
  * Antiepileptic agents. While not a strict rule out, this will be decided on a case-by-case basis
  * Antipsychotic agents. While not a strict rule out, this will be decided on a case-by-case basis

Where this trial is running

Los Angeles, California

• UCLA TMS Clinical and Research Service — Los Angeles, California, United States (RECRUITING)

Study contacts

• Principal investigator: Michael Leuchter, MD — University of California, Los Angeles
• Study coordinator: Cole Mathews

Conditions: Alzheimer&Amp, Amp, #39, s Disease, Alzheimer Disease, Dementia Alzheimer Type, Mild Alzheimer&Amp, Moderate Alzheimer&Amp