Precision Medicine for Dementia

(EVANTHEA Trial)

Recruiting in Palo Alto (17 mi)

+6 other locations

Overseen by Kat Toups, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

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

Must be taking: Aricept

Must not be taking: Psychoactive medications

Disqualifiers: Uncontrolled illness, Type 1 diabetes, Cancer, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

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.

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}

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}

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}

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.

Treatment Details

Interventions

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

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Walnut Creek Walnut Creek, CA

Rezilir Health Hollywood, FL

Kemper Cognitive Wellness Rocky River, OH

MaxWell Clinic, PLC Brentwood, TN

More Trial Locations

Who Is Running the Clinical Trial?

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

Four Winds Foundation Collaborator

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] Aducanumab (BIIB037), a human monoclonal antibody selective for aggregated forms of amyloid beta, is being investigated as a disease-modifying treatment for Alzheimer's disease (AD).

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

Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer's Disease. [2022] Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease that places a substantial burden on patients and caregivers. Aducanumab is the first AD therapy approved by the US Food and Drug Administration to reduce a defining pathophysiological feature of the disease, brain amyloid plaques. In the phase 3 clinical trial EMERGE (NCT02484547), aducanumab reduced clinical decline in patients with mild cognitive impairment (MCI) due to AD and mild AD dementia and confirmed amyloid pathology.

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] To identify the class of evidence for aducanumab use for the treatment of Alzheimer disease and present clinical considerations regarding use.

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

Estimated Annual Spending on Aducanumab in the US Medicare Program. [2023] This cross-sectional study examines upper bound and lower bound annualized Medicare costs for administering aducanumab to beneficiaries with the approved indications of mild cognitive impairment or mild dementia.

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

Aducanumab for Alzheimer's disease: Observations and opportunities. [2022] To analyse the overseas approval of aducanumab for Alzheimer's disease, in order to derive lessons of potential interest to individuals and groups involved in dementia drug development and regulation in Australia.

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

Practical Considerations in the Administration of Aducanumab for the Neurologist. [2022] Aducanumab (Aduhelm), developed by the biotechnology firm Biogen in Cambridge, MA, was approved using the less common accelerated approval pathway by the Federal Drug Administration (FDA) reserved for treatments that fill a significant unmet need.1 Its approval on June 7, 2021, has been met with an outpouring of opinions from prescribers, insurers, advocacy groups, and hospital systems regarding its risk-benefit profile.2-4 Originally approved for all forms of Alzheimer disease (AD), the FDA updated aducanumab's labeling on July 8, 2021, for "treatment in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, the population in which treatment was initiated in clinical trials."5 With 6 million people nationally in the United States who suffer from AD and an anticipated one-third of those who may now fulfill the criteria under the revised labeling, the implications of aducanumab's approval continue to generate national interest.6.

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

Aducanumab: First Approval. [2021] Aducanumab (aducanumab-avwa; Aduhelm™) is a human, immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid β. It has been co-developed by Biogen and Eisai under license from Neurimmune for the treatment of Alzheimer's disease. In June 2021, aducanumab received its first approval in the USA for the treatment of Alzheimer's disease. According to the US FDA prescribing information, treatment should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. Aducanumab is under regulatory review in Japan and in Europe. Its long-term safety and tolerability is being evaluated in a multinational phase 3b clinical study in patients with early Alzheimer's disease (mild cognitive impairment and mild Alzheimer's disease). This article summarizes the milestones in the development of aducanumab leading to this first approval for Alzheimer's disease.

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

What does aducanumab treatment of Alzheimer's disease mean for research on vascular cognitive disorders? [2023] •Controversial registration of aducanumab for Alzheimer's Disease•Aducanumab is the subject of post-licensing observational studies aiming to follow the effects of the drug•Given the high prevalence of cerebrovascular pathology it is important that these studies do not ignore vascular cognitive disorders•The studies may give detailed phenotyping data that may lead to knowledge of targets for treatments of patients with vascular cognitive disorders.

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

Making the Case for the Accelerated Withdrawal of Aducanumab. [2022] U.S. Food and Drug Administration-s (FDA) approval of aducanumab (Aduhelm® in the US) as a treatment for mild cognitive impairment of the Alzheimer type and Alzheimer-s disease has raised such major concerns about efficacy, safety, FDA processes, and regulatory capture that Biogen-s license to market this biologic should be immediately withdrawn. Aducanumab has not demonstrated benefit to patients, failed to meet regulatory guidelines, and is likely to cause both individual and societal harm.

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

Potent Activity of an Anti-ICAM1 Antibody-Drug Conjugate against Multiple Myeloma. [2021] New therapies have changed the outlook for patients with multiple myeloma, but novel agents are needed for patients who are refractory or relapsed on currently approved drug classes. Novel targets other than CD38 and BCMA are needed for new immunotherapy development, as resistance to daratumumab and emerging anti-BCMA approaches appears inevitable. One potential target of interest in myeloma is ICAM1. Naked anti-ICAM1 antibodies were active in preclinical models of myeloma and safe in patients, but showed limited clinical efficacy. Here, we sought to achieve improved targeting of multiple myeloma with an anti-ICAM1 antibody-drug conjugate (ADC).

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

Therapeutic potential of isatuximab in the treatment of multiple myeloma: Evidence to date. [2021] Management of multiple myeloma represents an ever changing paradigm with monoclonal antibodies adding the ability to treat patients with 3 and 4 drug regimens with acceptable toxicity profiles. In recent years, we have seen the FDA approve a number of regimens with both elotuzumab and daratumumab in combination with the standard approaches of immunomodulatory drugs, proteasome inhibitors, and steroids. Isatuximab is a naked, humanized IgG1 monoclonal antibody directed against CD38. With the recent FDA approval in March 2020, we seek to summarize the presented data to date and where this drug will fit into the future gestalt of myeloma therapy.

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

MonumenTAL Results for Talquetamab in Myeloma. [2023] Nearly three quarters of the 288 patients with relapsed/refractory multiple myeloma enrolled in the phase I/II MonumenTAL-1 trial of the investigational drug talquetamab experienced significant anticancer effects. A first-in-class, off-the-shelf bispecific antibody, talquetamab targets GPRC5D, which is highly expressed on malignant plasma cells but limited on normal cells, and recruits CD3-expressing T cells, activating an immune response.

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

An evaluation of isatuximab, pomalidomide and dexamethasone for adult patients with relapsed and refractory multiple myeloma. [2022] Despite therapeutic advances, myeloma remains an essentially incurable disease, with a median survival of approximately 8 - 10 years. Most patients will develop disease that is refractory to immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs), and treatment regimens containing drugs with different mechanisms of action are necessary. Isatuximab is one such novel agent, an anti-CD38 monoclonal antibody (MoAb), and is the second drug in this class after daratumumab. This paper will consider the current role for isatuximab with pomalidomide for the treatment of relapsed/refractory myeloma (RRMM).

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

[Diagnosing Alzheimer's dementia - a playground for academics or a sensible clinical measure?] [2022] The number of dementia cases continues to increase with Alzheimer's disease as the leading cause. The diagnostic workup of Alzheimer's dementia is complex, and its clinical relevance debatable considering the current lack of disease-modifying treatments. From this perspective, a stepwise diagnostic approach is recommended. Whenever Alzheimer's dementia is suspected, a patient' history a physical and psychiatric examination, neuropsychological tests, routine blood tests and standard cerebral imaging should be conducted. This allows in many cases a diagnosis to be given. In cases remaining unclear, modern biomarker tests are proving increasingly useful. Knowledge of the diagnosis is pivotal for the patients to assess the prognosis, to enable them to make plans for their future and to get access to available treatment. The approval of aducanumab in the USA and other promising monoclonal antibodies currently in phase 3-trials as well as the development of blood biomarkers give us hope for the future.