rTMS + Methylphenidate for Alzheimer's Disease

(REACT Trial)

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: Amphetamines

Disqualifiers: Depression, Agitation, Delusions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores ways to treat apathy, a lack of interest or enthusiasm, in individuals with early Alzheimer’s disease or similar conditions. Researchers are testing two approaches: using a non-invasive brain stimulation technique called repetitive transcranial magnetic stimulation (rTMS) alone, and in combination with the stimulant medication methylphenidate. The goal is to determine which method best improves symptoms of apathy. Individuals who have experienced apathy for at least four weeks and maintain a stable medication routine might be suitable for this study. As an unphased trial, this study offers a unique opportunity to contribute to pioneering research that could lead to new treatment options for apathy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that participants should have a stable dose of any medication affecting cognition or behavior for more than 4 weeks. You cannot participate if you are currently taking an amphetamine product.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study showed that repetitive transcranial magnetic stimulation (rTMS) is safe and effective for improving thinking and memory in people with Alzheimer's. This non-invasive treatment does not involve surgery or entering the body, and patients generally tolerate it well.

Methylphenidate, a medication often used to treat ADHD, has also been studied for its effects on apathy in Alzheimer's patients. Apathy refers to a lack of interest or enthusiasm. Multiple studies have shown that methylphenidate is safe and can help reduce apathy. For instance, a study with 200 participants found that methylphenidate was safe and effective for apathy, with no major safety concerns.

Both treatments are well-tolerated, with no major side effects reported in these studies. For those considering joining a trial, this information suggests that both treatments have a history of being safe for people with Alzheimer's. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Alzheimer's Disease because they use repetitive transcranial magnetic stimulation (rTMS), a technique that non-invasively stimulates brain regions involved in cognitive function. Unlike standard treatments such as cholinesterase inhibitors and memantine, which primarily aim to manage symptoms, rTMS could potentially enhance cognitive performance by directly targeting brain activity. Additionally, the combination of rTMS with methylphenidate, a stimulant known for boosting attention and alertness, offers a novel approach that might synergistically improve cognitive outcomes. These innovative strategies could pave the way for more effective interventions for Alzheimer's patients.

What evidence suggests that this trial's treatments could be effective for apathy in Alzheimer's disease?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can enhance thinking and memory in people with Alzheimer's disease. This improvement might alleviate symptoms like lack of interest or motivation. In this trial, some participants will receive only rTMS, while others will receive a combination of rTMS and methylphenidate. Studies have found that methylphenidate, a type of medication, can significantly reduce this lack of interest in Alzheimer's patients. It also eases the burden on caregivers by improving patient behavior. Combining rTMS with methylphenidate could offer a promising approach to addressing these symptoms in Alzheimer's disease. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for individuals with Alzheimer's or mixed Alzheimer's/vascular disease who have shown signs of apathy for at least 4 weeks. They must have a care partner available and be on stable medication doses that could affect cognition or behavior. People with major depression, agitation, delusions, hallucinations, medical issues preventing rTMS use, amphetamine use, CNS abnormalities, Tourette's syndrome or motor tics can't participate.

Inclusion Criteria

Patients experiencing apathy for at least 4 weeks

I have a care partner who is with me for at least 10 hours a week.

I've been on a stable dose of medication for over 4 weeks that could affect my thinking or behavior.

Exclusion Criteria

Current participation in another clinical trial

I am currently using an amphetamine product.

I experience severe restlessness, false beliefs, or see things that aren't there.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repetitive transcranial magnetic stimulation (rTMS) with or without methylphenidate

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Methylphenidate
• rTMS

Trial Overview The study is testing if rTMS can help reduce apathy in people with Alzheimer’s when they are already taking methylphenidate (a stimulant) and in those not on any medication for apathy. It aims to see if stimulating the brain non-invasively can improve interest and enthusiasm.

How Is the Trial Designed?

Group I: rTMS only Experimental Treatment 1 Intervention

repetitive transcranial magnetic stimulation (rTMS) only

Group II: rTMS + methylphenidate Experimental Treatment 2 Interventions

repetitive transcranial magnetic stimulation (rTMS) and methylphenidate

rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder
• Migraines
• Smoking cessation

Approved in European Union as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3902018/

Safety and Efficacy of Methylphenidate for Apathy in ... Methylphenidate treatment of apathy in Alzheimer's disease was associated with significant improvement in 2 of 3 efficacy outcomes and a trend toward improved ...

2. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2784538

Effect of Methylphenidate on Apathy in Patients With ... Methylphenidate may be useful for the treatment of apathy in individuals with Alzheimer disease, which can reduce symptoms and caregiver burden.

3. nia.nih.gov nia.nih.gov/news/ritalin-reduced-apathy-nia-funded-alzheimers-clinical-trial

Ritalin reduced apathy in NIA-funded Alzheimer's clinical trial Two daily doses of the stimulant methylphenidate safely reduced measures of apathy for six months among adults with Alzheimer's disease.

4. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/trc2.12403

Effects of methylphenidate on neuropsychiatric symptoms in ... Methylphenidate has been shown to improve apathy in patients with Alzheimer's disease (AD). The authors evaluated the impact of ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00495820

Methylphenidate for Apathy in Alzheimer's Dementia: A ... The purpose of the study is to determine the efficacy of methylphenidate over placebo in treating apathy in patients with Alzheimer's dementia.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S106474812400099X

Methylphenidate for Apathy in Alzheimer's Disease Dr. Rosenberg will present the safety and efficacy results of the ADMET2 trial with methylphenidate presenting a safe profile with a small to medium effect on ...