Senolytic Therapy for Alzheimer's Disease

(SToMP-AD Trial)

Not currently recruiting at 5 trial locations

Overseen By Sarah B Bohlman, MSL

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Anticoagulants, Chemotherapy, Anti-amyloid, others

Disqualifiers: Obesity, Neurologic disease, Substance abuse, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called senolytic therapy to determine its potential benefits for individuals with early-stage Alzheimer's disease or amnestic mild cognitive impairment, both of which impair memory and thinking. The study will assess the safety and effectiveness of this treatment, which combines two drugs, Dasatinib and Quercetin, against a placebo (a harmless pill resembling the actual treatment). Suitable candidates for this trial include those diagnosed with early Alzheimer's or mild memory issues and elevated levels of tau protein (a protein linked to Alzheimer's) in their brain. The trial aims to discover if senolytic therapy can improve symptoms and slow disease progression. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial allows participants to continue taking FDA-approved Alzheimer's medications like donepezil, rivastigmine, or galantamine if they have been on a stable dose for at least three months. However, certain medications, such as those affecting liver enzymes (CYP3A4, CYP2C8, CYP2C9, CYP2D6) or inducing cellular senescence, may need to be stopped. Participants on anticoagulants or H2 antagonists/proton pump inhibitors may need to adjust their medication schedule during the trial.

Is there any evidence suggesting that senolytic therapy is likely to be safe for humans?

Research has shown that using Dasatinib and Quercetin together as a treatment is generally safe. Studies have found that administering these drugs occasionally to older adults is both feasible and safe. In a small study, older adults with mild memory problems received these treatments, and the results indicated they were safe and well-tolerated.

Another study found that these drugs helped reduce some harmful brain changes without major safety issues. Overall, the evidence so far suggests that this combination can be used safely in people, especially when given at intervals.

This treatment is currently in Phase 2 of trials, indicating it has been tested for safety in smaller groups. This phase helps confirm these findings in a larger population. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Unlike the standard Alzheimer's treatments, which mainly target symptoms or aim to slow the disease's progression, senolytic therapy focuses on removing harmful senescent cells that accumulate in the brain. This approach is unique because it uses dasatinib and quercetin, two compounds known for their ability to clear out these dysfunctional cells. Researchers are excited about this treatment because it could potentially address one of the root causes of Alzheimer's, offering a new way to tackle the disease beyond just managing its symptoms.

What evidence suggests that senolytic therapy might be an effective treatment for Alzheimer's disease?

Research suggests that using Dasatinib and Quercetin in senolytic therapy might improve memory and thinking skills. Some studies have shown that this treatment aids learning and memory in animals, such as rats, by removing old cells that have stopped dividing, which can contribute to aging and disease. Other research indicates that this treatment can reach the brain, which is crucial for addressing brain conditions like Alzheimer's. In this trial, participants will receive either the Dasatinib and Quercetin combination or a placebo. These findings suggest that Dasatinib and Quercetin could help people with mild memory problems related to Alzheimer's. ^{1 3 6 7 8}

Who Is on the Research Team?

Miranda Orr, PhD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults aged 65 and older with mild cognitive impairment or early-stage Alzheimer's Disease, who have elevated tau protein levels. Participants must be on a stable dose of FDA-approved AD medications for at least three months, able to consent (or have a representative), and have a study partner. They should not plan extensive travel during the study and must speak English fluently.

Inclusion Criteria

Participants must have no travel plans that would interfere with scheduling visits following consent over the 12 months of study duration

Your total cholesterol should be less than 240 mg/dl, and your HbA1c level should be 7% or lower.

Your blood clotting tests (PT/PTT/INR) are normal.

Exclusion Criteria

I have not had a heart attack, chest pain, stroke, or mini-stroke in the last 6 months.

You cannot have an MRI if you are claustrophobic, have metal implants, or a cardiac pacemaker.

I cannot take medicine by mouth.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive senolytic therapy or placebo for 12 consecutive weeks, with 2 days of dosing followed by a 13-day no-drug period for 6 rounds

12 weeks

1 in-person visit per cycle, additional telephone visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, with adverse events collected up to week 48

36 weeks

In-person and telephone visits

What Are the Treatments Tested in This Trial?

Interventions

• Senolytic Therapy

Trial Overview The SToMP-AD Study is testing the safety and effectiveness of senolytic therapy using Dasatinib plus Quercetin compared to placebo capsules in slowing down Alzheimer's progression in patients with positive tau PET scans.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Dasatinib (D) is given as (1) 100mg capsule daily for 2 consecutive days (Sprycel®, Bristol Myers Squibb). Quercetin (Q) will be given as (4) 250 mg capsules daily (total 1000 mg daily) for the same 2 consecutive days (Thorne Research). Both are administered orally.

Group II: Placebo Placebo Group 1 Intervention

Matching placebo capsules following the same administration protocol as the experimental treatment - administered once daily (1st dose of each cycle will be given, supervised, at the clinic visit; the 2nd dose will be taken at home) for 2 consecutive days followed by a 13-day (+/- 2 day) no-drug period for 12 consecutive weeks for 6 rounds of administration.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Wake Forest University Health Sciences

Collaborator

Trials

1,432

Recruited

2,506,000+

The University of Texas Health Science Center at San Antonio

Collaborator

Trials

486

Recruited

92,500+

Published Research Related to This Trial

The phase I clinical trial involving 5 early-stage Alzheimer's patients demonstrated that the senolytic therapy dasatinib and quercetin was well-tolerated, with no early discontinuations and confirmed CNS penetrance of dasatinib in cerebrospinal fluid.

While the treatment did not show significant cognitive improvements, it provided safety data and insights into potential senolytic effects, indicating a need for further studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial. Gonzales, MM., Garbarino, VR., Kautz, TF., et al.[2023]

In a 12-week pilot study involving 5 participants with early-stage Alzheimer's disease, the combination of dasatinib and quercetin was well-tolerated, showing safety and feasibility without significant adverse effects or early discontinuations.

The treatment successfully penetrated the central nervous system, with dasatinib detected in cerebrospinal fluid, suggesting potential for targeting cellular senescence in Alzheimer's, although cognitive improvements were not observed in this small trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Senolytic therapy to modulate the progression of Alzheimer's Disease (SToMP-AD) - Outcomes from the first clinical trial of senolytic therapy for Alzheimer's disease. Gonzales, MM., Garbarino, VR., Kautz, T., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10168460/

Senolytic therapy to modulate the progression of Alzheimer's ... Primary outcomes were to assess blood-brain barrier penetrance of the senolytic drugs Dasatinib (D) and Quercetin (Q) (D+Q). Secondary outcomes explored target ...

2. thelancet.com thelancet.com/journals/ebiom/article/PIIS2352-3964(25)00056-8/fulltext

A pilot study of senolytics to improve cognition and mobility ... Furthermore, the preliminary data suggest that Dasatinib and Quercetin may improve memory/cognition by modulating specific markers of senescence ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2213231725002290

Long-term senolytic therapy with Dasatinib and Quercetin ... Importantly, the long-term D + Q regimen significantly alleviated the degeneration of retinal structures and function in 8-month-old Abca4−/−Rdh8−/− mice, and ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04063124

Study Details | NCT04063124 | Senolytic Therapy to ... This combination of drug therapy has been shown to affect dying cells in humans with other chronic illnesses and in Alzheimer's mice models.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8833137/

Combination of dasatinib and quercetin improves cognitive ... Aged rats following D+Q treatment displayed improved learning abilities and effective acquisition of spatial short- and long-term memory of a new place compared ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2274580724003571

Senolytic Therapy to Modulate the Progression of ... Intermittent dosing of the senolytics, dasatinib plus quercetin, has shown an acceptable safety profile in clinical studies for other senescence-associated ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05422885?intr=Dasatinib%20%2B%20Quercetin&rank=2

Safety and Feasibility of Dasatinib and Quercetin in Adults ... The purpose of this pilot study is to demonstrate the safety and feasibility of administering intermittent doses of Dasatinib and Quercetin (D+Q) in older ...

8. scholars.uthscsa.edu scholars.uthscsa.edu/en/publications/senolytic-therapy-to-modulate-the-progression-of-alzheimers-disea-2

Outcomes from the first clinical trial of senolytic therapy for ... Clearance of senescent cells using the senolytic compounds dasatinib (D) and quercetin (Q) reduced neuropathological burden and improved ...