Precision Medicine for Dementia

(EVANTHEA Trial)

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

72 Participants Needed

Trial Summary

What is the purpose of this trial?

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 dementia. Precision medicine approach starts with the completion of many tests and then the study doctor uses the test results to carefully prepare a treatment plan that is best for the individual person to help treat many of the underlying causes of mild cognitive impairment or early-stage dementia. The main question the study aims to answer is: • Does the precision medicine approach improve memory (cognitive function) better than the current standard-of-care treatment in people with mild cognitive impairment or early-stage dementia during a 9-month treatment period? This is a randomized clinical trial which means that a group of people that meet the study requirements will be assigned at random or by chance (like toss of a coin) to receive either the precision medicine treatment or the current gold standard (standard-of-care). People assigned to the precision medicine group will receive precision medicine for 9-months while those assigned to the standard-of-care group will follow that approach for 9-months, followed by an opportunity to receive up to six months of precision medicine, if desired. Participants will be asked to: * Have their blood drawn for extensive lab testing and collect urine and stool samples as well * Carefully follow instructions received from their study doctor and study team * Make lifestyle changes as prescribed by the study doctor and study team based on your precision medicine program * Take supplements and medications prescribed by the study doctor. * Once officially in the study (after meeting study entry or screening requirements), participate in ten (10) monthly visits with the study doctor, and other members of the study team as scheduled. * Complete cognitive tests at scheduled visits during the study * Have a study partner with you during visits and to help support you on the program Researchers will compare test results between the two study groups to see if the precision medicine approach improves those tests results over the time of the study, resulting in the improvement of cognition over a 9-month treatment period.

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.

What data supports the effectiveness of the drug Aduhelm (aducanumab-avwa) for dementia?

Research shows that Aduhelm (aducanumab-avwa) can reduce brain amyloid plaques, which are linked to Alzheimer's disease, and slow down the decline in patients with mild cognitive impairment or mild Alzheimer's dementia. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Aduhelm (aducanumab) for dementia?

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 with mild cognitive impairment or mild Alzheimer's dementia. ^{1 2 3 4 5}

Is aducanumab (Aduhelm) generally safe for humans?

Aducanumab (Aduhelm) has been approved for treating Alzheimer's disease, but its safety has been questioned, with concerns about potential harm and lack of demonstrated benefits. Its long-term safety is still being evaluated in ongoing studies. ^{5 6 7 8 9}

Is aducanumab (Aduhelm) generally safe for humans?

Aducanumab (Aduhelm) has been approved for treating Alzheimer's disease, but its safety has been questioned, with concerns about potential harm and the need for further evaluation in ongoing studies. ^{5 6 7 8 9}

How is the drug Aduhelm (aducanumab-avwa) unique in treating Alzheimer's dementia?

Aduhelm (aducanumab-avwa) is unique because it is a monoclonal antibody designed to target and reduce amyloid-beta plaques in the brain, which are believed to play a role in Alzheimer's disease progression. This mechanism of action is different from other treatments that primarily focus on managing symptoms rather than modifying the disease itself. ^{10 11 12 13 14}

What makes the drug Aduhelm unique for treating Alzheimer's dementia?

Aduhelm (aducanumab) is unique because it is a monoclonal antibody designed to target and reduce amyloid-beta plaques in the brain, which are believed to play a role in Alzheimer's disease progression. This approach is different from other treatments that primarily focus on managing symptoms rather than modifying the disease itself. ^{10 11 12 13 14}

Research Team

Dale Bredesen, MD

Principal Investigator

Alzheimer's Prevention and Reversal Project, Inc.

Kat Toups, MD

Principal Investigator

Bay Area Wellness

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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]

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]

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 (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]

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]

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 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]

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]

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]

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]

References

1. United States 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. [2020]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer's Disease. [2022]

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

Aducanumab Use in Symptomatic Alzheimer Disease Evidence in Focus: A Report of the AAN Guidelines Subcommittee. [2023]

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

Estimated Annual Spending on Aducanumab in the US Medicare Program. [2023]

5. England pubmed.ncbi.nlm.nih.gov

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

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

Practical Considerations in the Administration of Aducanumab for the Neurologist. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Aducanumab: First Approval. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

What does aducanumab treatment of Alzheimer's disease mean for research on vascular cognitive disorders? [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Making the Case for the Accelerated Withdrawal of Aducanumab. [2022]

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

Potent Activity of an Anti-ICAM1 Antibody-Drug Conjugate against Multiple Myeloma. [2021]

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

Therapeutic potential of isatuximab in the treatment of multiple myeloma: Evidence to date. [2021]

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

MonumenTAL Results for Talquetamab in Myeloma. [2023]

13. England pubmed.ncbi.nlm.nih.gov

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

14. Germany pubmed.ncbi.nlm.nih.gov

[Diagnosing Alzheimer's dementia - a playground for academics or a sensible clinical measure?] [2022]