Senolytic Therapy for Alzheimer's Disease

(SToMP-AD Trial)

Recruiting at 4 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

48 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing drugs in older adults with early signs of cognitive decline and tau protein tangles in their brains. These drugs aim to remove old, damaged cells to reduce inflammation and other issues, potentially improving symptoms. The combination of dasatinib and quercetin has shown an acceptable safety profile in other conditions.

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.

What data supports the effectiveness of the drug Senolytic Therapy for Alzheimer's Disease?

Research shows that in mouse models, senolytic therapy, which involves clearing out old, damaged cells, reduced harmful protein buildup and inflammation in the brain, and improved brain health. Early human trials with the drugs dasatinib and quercetin, part of senolytic therapy, have shown they can reach the brain and are safe, but more studies are needed to confirm their effectiveness in treating Alzheimer's. ^{1 2 3 4 5}

Is senolytic therapy safe for humans?

Senolytic therapy, using dasatinib and quercetin, has shown an acceptable safety profile in clinical studies for conditions related to aging, including Alzheimer's disease. In a small trial with Alzheimer's patients, the treatment was well-tolerated with no early discontinuations, supporting its safety and feasibility. ^{1 2 3 5 6}

How does senolytic therapy differ from other Alzheimer's disease treatments?

Senolytic therapy is unique because it targets and clears senescent cells (damaged cells that stop dividing and contribute to aging and disease) to reduce inflammation and improve brain function, unlike other treatments that primarily focus on reducing amyloid plaques. This approach aims to address the underlying aging process, which is a major risk factor for Alzheimer's disease. ^{1 2 5 7 8}

Research Team

Miranda Orr, PhD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Senolytic Therapy to Modulate the Progression of Alzheimer's Disease (SToMP-AD): A Pilot Clinical Trial. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Translating the Biology of Aging into New Therapeutics for Alzheimer's Disease: Senolytics. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Senolytic therapy in mild Alzheimer's disease: a phase 1 feasibility trial. [2023]

4. United States 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. [2023]

5. Ireland pubmed.ncbi.nlm.nih.gov

A geroscience motivated approach to treat Alzheimer's disease: Senolytics move to clinical trials. [2022]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Cellular Senescence and Senolytic Agents: Recent Updates on Their Role and Applications. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Senolytic drugs: from discovery to translation. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Recent advances in the discovery of senolytics. [2022]