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RecruitingPhase 1 / Phase 2

Large-coil Parietal Repetitive Transcranial Magnetic Stimulation (rTMS) for Alzheimer Disease (AD)

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
55 Years to 100 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: Questionnaires

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Additionally, participants and their caregivers will complete brief weekly check-ins at each treatment during the study, as well as questionnaires related to the study blinding at multiple timepoints."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests deep rTMS, which uses magnetic pulses to stimulate the brain, in adults ages 55–100 with early memory problems or mild-to-moderate dementia due to Alzheimer's disease. Researchers will compare real treatment with placebo treatment to see if it is practical, tolerable, and may help memory or cause positive brain changes.

The goal of this clinical trial is to learn if using large-coil (or "deep") repetitive transcranial magnetic stimulation (rTMS) targeting the precuneus and surrounding areas is feasible, tolerable, and potentially efficacious for memory in Alzheimer's Disease. Previous work studying rTMS in Alzheimer's is mixed, but recent work studying rTMS of the precuneus is encouraging for both its short-term and long-term effects. The main questions this study aims to answer are: * Is deep rTMS of the precuneus feasible and tolerable in Alzheimer's? * Are there signs of positive brain changes in response to deep rTMS? * Is deep rTMS potentially efficacious for memory in Alzheimer's? Researchers will compare active stimulation to placebo stimulation while obtaining memory testing and measurements of the brain (imaging, scalp electrode measurements, bloodwork) to see if active treatment works to treat Mild Cognitive Impairment (MCI) and mild-to-moderate dementia due to Alzheimer's disease. Participants will: * Engage with memory testing, brain scans, and bloodwork during a comprehensive assessment * Visit the clinic 3 times for 12 consolidated rTMS sessions, followed by 8 once weekly maintenance visits * Be offered a full open-label active treatment course after completing their treatment course if they are initially in the placebo group

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be ages 55–100 and agree to join through the informed consent process.
  • Have a caregiver or study partner who can attend every visit, plus a backup decision-maker who can attend the consent visit.
  • Have Alzheimer's disease at clinical stage 3, 4, or 5, confirmed by a brain scan, blood test, or spinal fluid test.
  • Score 12–25 on the MoCA, a test of memory and thinking.
  • Score below 6 on the GDS, a depression screening test.
  • Have used a memory treatment for at least 2 months, had an unsuccessful trial with no plan to retry, or have no treatment trial planned during the study.
  • Have no changes in medicines or other treatments for depression, anxiety, ADHD, or psychosis for at least 2 weeks before the study.

Who can't join

  • Cannot or do not agree to the informed consent process; are pregnant or might be pregnant; or are not fluent in English for testing.
  • Have severe dementia, or memory and thinking problems mainly caused by something other than Alzheimer's disease.
  • Have an ongoing substance use disorder, or substance misuse in the past 6 months, other than nicotine or caffeine.
  • Have had a stroke, a head injury with loss of consciousness, another major brain or nerve disorder, or seizures; or have a parent, sibling, or child with a seizure disorder.
  • Have poorly controlled high blood pressure, heart disease, disease of brain blood vessels, or another major active illness that affects thinking or safe participation.
  • Cannot safely have TMS or MRI because of issues such as fear of tight spaces, certain metal or implants, surgery within 60 days, or past abnormal MRI findings unrelated to dementia.
  • Have had TMS before (randomized stage only), are in another study testing memory treatment, or changed memory treatment doses in the past 2 months or plan to change them. Started an Alzheimer's antibody drug, such as lecanemab or donanemab, in the past 6 months, or had treatment-related brain swelling or bleeding called ARIA.
  • Use, or used in the past 2 weeks, anticholinergic medicines, sedating antihistamines, or drugs with similar effects, such as mirtazapine or some older antidepressants. Medicines for anxiety, pain, seizures, or psychosis in certain drug groups are reviewed case by case.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria: * Agreement to participate in study and able to complete informed consent process * Have a caregiver or study partner who can accompany them to all study visits * Have a known alternate surrogate decision-maker (in case needed) who can be present for informed consent * Established diagnosis of biomarker-positive (amyloid-PET, plasma or CSF amyloid ratio or phosphorylated tau) mild-moderate (clinical stages 3, 4, and 5) Alzheimer's Disease based on the 2024 Alzheimer's Association Framework * Age 55-100 at the start of the study. * Screening MOCA 12-25 (\< 26, \> 11) * Screening GDS score \<6 * Either 1) treated with memory-enhancing medication (cholinesterase inhibitor or other medications or treatments) 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 (or other treatments) for the treatment of depression, anxiety, ADHD, or psychosis for 2 weeks prior to the study Exclusion Criteria: * Unwilling or unable to provide informed consent as outlined below * Currently pregnant or potentially pregnant * Diagnosis of a dementia or cognitive disorder primarily or exclusively due to a cause other than Alzheimer's Disease * Diagnosis of severe Dementia (CDR \> 2.0/ AA clinical stage 6) 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, specified here for cognitive testing purposes) * 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 unrelated to a potential participant's dementia. * For the randomized stage only-has a history of prior TMS treatment (not TMS naïve) * Currently enrolled in an interventional memory-enhancement study * Alteration in cognitive-enhancement medication (or other treatment) 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) * Has started treatment with lecanemab, donanemab, or any other monoclonal antibody for Alzheimer's Disease within the past 6 months OR has a history of treatment complicated by amyloid-related imaging abnormalities (ARIA) * 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 * Opioid. 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

Study sites (1)

CA