Precision Medicine for Dementia

(EVANTHEA Trial)

Not currently recruiting at 6 trial locations

Overseen By Evanthea Project Manager

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alzheimer's Prevention and Reversal Project, Inc.

Must be taking: Aricept

Must not be taking: Psychoactive medications

Disqualifiers: Uncontrolled illness, Type 1 Diabetes, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 11

Duration: 9 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a personalized treatment plan can enhance memory more effectively than standard care for individuals with mild memory issues or early-stage dementia. Participants will receive either a custom plan based on several tests or follow the standard treatment, and researchers will compare the results. Ideal candidates for this trial include those with mild memory loss or early dementia, who can make lifestyle changes, and have a supportive partner to assist with study requirements. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment.

Do I need to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it requires that all existing medical conditions and medication dosages be stable. If you are taking Aricept, you must have been on a stable dose for at least 90 days before the study and remain on the same dose throughout the study.

Will I have to stop taking my current medications?

The trial requires that all existing medical conditions and any current medication dosages must be stable. Participants taking Aricept must have been on a stable dose for at least 90 days before the study and agree to remain on the same dose throughout the study. If you are using psychoactive medications that impact cognition, you may need to discontinue them if eligible.

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

Research has shown that precision medicine can be safe for people with mild memory problems or early dementia. Studies have found that personalized treatments, including specific medications, supplements, and lifestyle changes, typically do not cause serious side effects. These treatments rely on individual test results, enabling doctors to tailor a plan to each person's unique health needs. While some side effects might occur, they are generally mild, such as headaches or minor stomach issues. This approach often involves support from health professionals like nutritionists and fitness trainers, who help manage any side effects and enhance the overall treatment experience. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Precision Medicine approach for dementia because it offers a highly personalized treatment plan unlike the standard options like medication management, lifestyle changes, and cognitive therapies. This approach starts with a detailed analysis of each individual's cognitive issues and tailors a unique program that can include supplements, medications, dietary changes, and even advanced treatments like neurostimulation and hyperbaric oxygen therapy. Additionally, it integrates comprehensive lifestyle coaching with support from nutritionists and fitness trainers, aiming to address the root causes of cognitive impairment in a holistic manner.

What evidence suggests that this trial's treatments could be effective for mild cognitive impairment or early-stage dementia?

Research has shown that precision medicine for treating dementia aims to address various causes of memory and thinking problems. In this trial, participants in Group A will receive a precision medicine approach, including personalized treatments such as specific medications, lifestyle changes, and supplements based on individual test results. Although limited data currently proves its effectiveness, this method shows promise by targeting multiple factors that might lead to dementia. By focusing on each person's unique needs, it aims to slow memory loss in individuals with mild cognitive impairment or early-stage dementia. Early signs suggest it might enhance thinking skills, but stronger evidence is needed for confirmation. ^{6 7 8 9 10}

Who Is on the Research Team?

Dale Bredesen, MD

Principal Investigator

Alzheimer's Prevention and Reversal Project, Inc.

Kat Toups, MD

Principal Investigator

Bay Area Wellness

Are You a Good Fit for This Trial?

This trial is for adults aged 45-76 with early dementia or mild cognitive impairment who can follow a treatment plan including diet, lifestyle changes, and medications. They need to have a supportive partner, live close to the study site, be proficient in English, use a computer/smartphone, and agree to home evaluations. Excluded are those with major psychiatric issues unrelated to cognitive decline or severe brain injury.

Inclusion Criteria

Willing and able to follow the protocol procedures and testing, including changes in diet, lifestyle, supplements, and medications

Willingness to comply with COVID prevention precautions

You must be willing to undergo an MRI and a special scan to check your heart arteries.

Exclusion Criteria

You have a medical condition that makes it unsafe for you to have an MRI scan.

I am a woman going through menopause and choose not to use hormone therapy.

I have not used specific diets or holistic programs that could affect this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either precision medicine or standard-of-care treatment for mild cognitive impairment or early-stage dementia

9 months

10 monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Open-label extension (optional)

Participants in the standard-of-care group may opt into a 6-month precision medicine treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Hormones and Medications tailored to lab tests, combined with devices that support stress management and brain exercises
• Lifestyle including diet, exercise, stress management
• Precision Medicine Approach
• Standard-of-Care

Trial Overview The trial tests if personalized medicine based on extensive lab tests improves memory better than standard care over nine months. Participants will receive tailored treatments involving hormones, medications, stress management devices and brain exercises versus standard lifestyle advice.

How Is the Trial Designed?

Group I: Group A (Precision Medicine) Experimental Treatment 3 Interventions

Precision Medicine approach starts with a battery of tests and questionnaires to determine a person's underlying causes of cognition impairment. A custom treatment program is developed and prescribed by the investigator based on the test results and includes a combination of: supplements, medications, hormone therapy, dietary changes, exercise program, brain exercises, stress management, sleep tracking. Additional treatments may include QEEG and photobiomodulation, neurostimulation, neurofeedback and/or hyperbaric oxygen treatment (additional treatment are only available at select sites). Participants in this Group will also be supported in their program by a nutritionist, health coach, and fitness trainer, in addition to the study doctor. Tracking of study activities may also be required in the form of diaries, and devices will be used to track some of their activities such as sleep, stress, diet and exercise.

Group II: Group B (Standard-of-Care) Active Control 1 Intervention

Standard-of-care treatment will be based on the practice guideline of hte Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Participants in this group will be guided according to the recommendations which include recommending: * participation in cognitively and socially-stimulation activities * regular exercise * ensuring quality sleep including treatment of any sleep apnea * control of any modifiable risk factors such as blood pressure, diabetes, cholesterol, and avoidance of tobacco use * evaluation by a primary care physician * adherence to a healthy and balanced diet * consult a neurologist or primary care physician regarding use of medications * consult with their primary care physician to identify any worsening conditions

Precision Medicine Approach is already approved in United States for the following indications:

Approved in United States as Aduhelm for:

• Alzheimer's disease in patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) or mild dementia stage of the disease

Who Is Running the Clinical Trial?

Alzheimer's Prevention and Reversal Project, Inc.

Lead Sponsor

Trials

1

Recruited

70+

Four Winds Foundation

Collaborator

Trials

1

Recruited

70+

Published Research Related to This Trial

Isatuximab, an anti-CD38 monoclonal antibody, combined with pomalidomide and dexamethasone, provides a new treatment option for patients with relapsed/refractory multiple myeloma (RRMM) who are resistant to other therapies, addressing a significant unmet clinical need.

The review highlights the safety and efficacy of isatuximab, suggesting it could be an important addition to treatment regimens for RRMM, especially for patients with a poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of isatuximab, pomalidomide and dexamethasone for adult patients with relapsed and refractory multiple myeloma. Piggin, A., Prince, HM.[2022]

Aducanumab, a drug for Alzheimer's Disease, is currently under post-licensing observational studies to monitor its effects and efficacy after its controversial approval.

These studies are crucial as they will also focus on cerebrovascular issues, which are common in Alzheimer's patients, potentially leading to better treatment strategies for vascular cognitive disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What does aducanumab treatment of Alzheimer's disease mean for research on vascular cognitive disorders? Wallin, A., Alladi, S., Black, SE., et al.[2023]

Aducanumab, approved by the FDA for treating mild cognitive impairment and Alzheimer's disease, has raised significant concerns regarding its efficacy and safety, with claims that it has not shown any real benefit to patients.

Critics argue that the approval process for aducanumab did not meet regulatory guidelines and that its continued use could lead to harm for both individuals and society as a whole.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Making the Case for the Accelerated Withdrawal of Aducanumab. Whitehouse, PJ., Saini, V.[2022]

The study provides an analysis of the annualized Medicare costs associated with administering aducanumab to patients with mild cognitive impairment or mild dementia, highlighting the financial implications of this treatment.

By examining both upper and lower bound costs, the research offers insights into the potential economic burden on the healthcare system for beneficiaries receiving this specific Alzheimer's treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimated Annual Spending on Aducanumab in the US Medicare Program. Mafi, JN., Leng, M., Arbanas, JC., et al.[2023]

The analysis of aducanumab's overseas approval highlights the importance of optimizing clinical trial designs to better meet regulatory standards and patient needs in dementia drug development.

Engaging with patients and advocacy groups can enhance the patient-clinician relationship, potentially leading to improved satisfaction with treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aducanumab for Alzheimer's disease: Observations and opportunities. Pridmore, W.[2022]

Aducanumab, the first FDA-approved therapy for Alzheimer's disease, has been shown to reduce clinical decline in patients with mild cognitive impairment and mild dementia, based on data from the phase 3 EMERGE trial.

Long-term modeling predicts that aducanumab treatment can lead to significant benefits, including an increase of 0.65 quality-adjusted life-years (QALYs) per patient and a delay in the progression to more severe stages of Alzheimer's, providing both clinical and socioeconomic advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer's Disease. Herring, WL., Gould, IG., Fillit, H., et al.[2022]

The anti-ICAM1 antibody-drug conjugate (ADC) demonstrated strong anti-myeloma effects in laboratory tests and in live models, indicating its potential as a new treatment option for multiple myeloma.

ICAM1 is highly expressed on myeloma cells, especially in patients who are resistant to current therapies, suggesting that targeting ICAM1 could be an effective strategy for treating relapsed or refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent Activity of an Anti-ICAM1 Antibody-Drug Conjugate against Multiple Myeloma. Sherbenou, DW., Su, Y., Behrens, CR., et al.[2021]

A stepwise diagnostic approach for Alzheimer's dementia is essential, involving patient history, examinations, neuropsychological tests, blood tests, and imaging, which can often lead to a diagnosis.

The recent approval of aducanumab and the development of promising monoclonal antibodies and blood biomarkers offer hope for future treatments, highlighting the importance of accurate diagnosis for patient prognosis and planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Diagnosing Alzheimer's dementia - a playground for academics or a sensible clinical measure?] Tatò, M., Perneczky, R.[2022]

Aducanumab, a monoclonal antibody targeting amyloid β, was approved by the FDA in June 2021 for treating Alzheimer's disease in patients with mild cognitive impairment or mild dementia, based on clinical trials conducted in this specific population.

The long-term safety and tolerability of aducanumab are currently being assessed in a multinational phase 3b clinical study, as there is no data on its effectiveness or safety for patients at different stages of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aducanumab: First Approval. Dhillon, S.[2021]

Isatuximab, a humanized IgG1 monoclonal antibody targeting CD38, was approved by the FDA in March 2020, adding a new option for treating multiple myeloma.

The use of monoclonal antibodies like isatuximab, along with other therapies such as immunomodulatory drugs and proteasome inhibitors, allows for more complex treatment regimens (3 to 4 drugs) while maintaining acceptable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of isatuximab in the treatment of multiple myeloma: Evidence to date. Richter, J., Sanchez, L., Thibaud, S.[2021]

In the MonumenTAL-1 trial, nearly 75% of the 288 patients with relapsed/refractory multiple myeloma showed significant anticancer effects from the investigational drug talquetamab.

Talquetamab is a first-in-class bispecific antibody that targets GPRC5D on malignant plasma cells while sparing normal cells, effectively activating T cells to mount an immune response against the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MonumenTAL Results for Talquetamab in Myeloma. [2023]

Aducanumab has been shown to be safe and well-tolerated in a Class I clinical trial with doses up to 30 mg/kg, while three Class II studies indicated it can reduce amyloid deposition in the brain compared to placebo.

However, the efficacy of aducanumab in improving clinical outcomes was uncertain, as it either had no significant effect or only slightly reduced worsening of dementia symptoms, and it was associated with a higher risk of adverse effects, such as amyloid-related imaging abnormalities in about 40% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aducanumab Use in Symptomatic Alzheimer Disease Evidence in Focus: A Report of the AAN Guidelines Subcommittee. Day, GS., Scarmeas, N., Dubinsky, R., et al.[2023]

Aducanumab, a monoclonal antibody targeting amyloid beta, was generally well tolerated at doses up to 30 mg/kg in patients with mild-to-moderate Alzheimer's disease, with no severe adverse events reported.

At the highest dose of 60 mg/kg, some patients experienced serious adverse events related to amyloid-related imaging abnormalities, but these resolved within 8 to 15 weeks, indicating a need for careful monitoring at higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer's disease. Ferrero, J., Williams, L., Stella, H., et al.[2020]

Aducanumab (Aduhelm) was approved by the FDA on June 7, 2021, through the accelerated approval pathway, aimed at addressing a significant unmet need in treating Alzheimer's disease (AD).

The FDA later revised its approval to specifically target patients with mild cognitive impairment or mild dementia, reflecting the population studied in clinical trials, which could potentially benefit around 2 million people in the U.S.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical Considerations in the Administration of Aducanumab for the Neurologist. Coerver, K., Yu, MM., D'Abreu, A., et al.[2022]

Citations

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One step forward to personalized medicine? - PMC In particular, there has been substantial criticism of the perceived low efficacy of Aduhelm as measured by the primary endpoint of two pivotal ...

2. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/2792897

What to Know About the Alzheimer Drug Aducanumab ... Aducanumab does not cure or reverse Alzheimer disease. In 2 clinical trials, after 18 months it reduced amyloid plaque levels, but that did not ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK573062/

Aducanumab - StatPearls - NCBI Bookshelf - NIH Aducanumab is approved to treat Alzheimer disease in patients who have MCI-AD or who are in the mild dementia stage of the disease.[11][12][11] ...

4. withpower.com withpower.com/trial/phase-3-dementia-5-2023-0feb2

Precision Medicine for Dementia (EVANTHEA Trial) Research shows that Aduhelm (aducanumab) can reduce brain amyloid plaques, which are a key feature of Alzheimer's disease, and slow down the decline in patients ...

5. alzheimers.org.uk alzheimers.org.uk/blog/what-is-aducanumab-dementia-drug-people-with-alzheimers-disease

What is Aducanumab and what could this dementia drug ... The EMERGE trial data showed a positive effect in people given Aducanumab compared to placebo. The ENGAGE trial however only demonstrated a clinical benefit in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05894954

Precision Medicine Approach for Early Dementia & Mild ... The goal of this clinical trial is to compare a precision medicine approach to the standard-of-care for people with mild cognitive impairment or early-stage ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9953731/

The Future of Precision Medicine in the Cure of Alzheimer's ... Significant improvements in diagnosis, treatments, and mitigation of AD are likely to result from the development and application of a comprehensive approach ...

8. trialstoday.org trialstoday.org/trial/NCT05894954

Precision Medicine Approach for Early Dementia & Mild ... The goal of this clinical trial is to compare a precision medicine approach to the standard-of-care for people with mild cognitive impairment or ...

9. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.14043

Precision diagnosis of cognitive impairment due to ... Precision diagnosis is needed to identify patients for AAMA therapy whose cognitive impairment is in the appropriate severity range.

10. frontiersin.org frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1213968/full

A how-to guide for a precision medicine approach ... This study includes de-identified cases and reviews of the underlying etiology and pathology of Alzheimer's and available therapies to exemplify diagnostic and ...