Precision Medicine Approach for Early Dementia & Mild Cognitive Impairment

Last updated: March 7, 2025
Sponsor: Alzheimer's Prevention and Reversal Project, Inc.
Overall Status: Active - Not Recruiting

Phase

3

Condition

Mild Cognitive Impairment

Alzheimer's Disease

Memory Loss

Treatment

Precision Medicine Approach

Hormones and Medications tailored to lab tests, combined with devices that support stress management and brain exercises

Lifestyle including diet, exercise, stress management

Clinical Study ID

NCT05894954
EVANTHEA-2023
  • Ages 45-76
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Provide signed informed consent

  • Adults of any gender, race, or ethnicity and aged 45 to 76 years at time ofenrollment

  • Cognitive impairment or early-stage dementia as demonstrated by combination of AQ-21score >4 and either:

  • MoCA 18-26, inclusive, or

  • greater than or equal 2 scores in the bottom 50th percentilve for NCI or ExecutiveFunction, Verbal, Visual, or Composite sub-tests

  • Proficient in spoken and written English for informed consent and study procedures

  • Have a willing and able study partner to support participant with compliance and allaspects of teh protocol and provide input for subjective ratings of theparticipant's cognitive status. The study partner must interact with teh participantfrequently (live with or have daily contact with participant), and have sufficientlyclose relationship to observe and understand participant's difficulties with memorand activities of daily living.

  • All exisiting medical conditions and any current medication dosages must be stable

  • Have regular access to computer and internet connection and an iOS or AndroidSmartphone or tablet capable of connecting to devices and applications used in thestudy

  • Ability to use a computer and web interface, or have readily available assistance tofacilitate the use of a computer and web interface

  • Ability to converse with a coach or provider virtually to access the virtualcoaching aspects of the treatment approach

  • Willing and able to follow the protocol procesured and testing, including changes indiet, lifestyle, supplements, and medications

  • Willing to have at least one home visit by the study health coach, including homeevaluation for toxins or mold

  • Willingness to remediate and/or move away from identifies sources of toxicity suchas molds or other toxins or infections or dental decay

  • Willingness to comply with COVID prevention precautions

  • Participants taking Aricept will be considered if they have been using Aricept forat least 90 days prior to study adminission. Must be on a stable dose for at least 90-days prior to screening and agree to remian on the same dose throughout thecourse of the study.

  • Women who are premenopausal and sexually active must be willing to use appropriatecontraception and have repeated pregnancy tests as indicated

  • Willing to have an MRI and coronary artery calcium scan

  • Live within 1-1.5 hours of the study site

  • Women only: willing to complete the health screening exams and remediate any healthissues detected during these screening exams: 1) Mammogram within 12 months ofrandomization; 2) Pelvic exam within 12 moths for women less than 60 years or pelvicexam within 24 months if 60 years or older.

Exclusion

Exclusion Criteria:

  • Presence of any uncontrolled major medical illness, seizures, or cardiovasculardisease

  • Diagnosis of Type 1 Diabetes

  • Presence of any major psychiatric diagnoses that impact the performance ofactivities of daily living or functioning, other than those related to cognitivedecline

  • Use of psychoactive medications known to impact cognition, unless willing andeligible to discontinue

  • Use of chronic anticoagulation therapy, other than prophylactic aspirin orproteolytic enzymes, or a history of recurrent deep vein thrombosis

  • MRI findings of hydrocephalus, focal stroke, extinsive white matter disease or braintumor

  • Prior traumatic brain injury of sufficient severity to impact functioning on aregular basis

  • Diagnosis of cancer in past 5 years, or any history or breast cancer; exclusive ofmelanoma skin cancers or ductal carcinoma in situ.

  • Positive test for HIV, Hepatitis C, or RPR (rapid plasma reagin)

  • Menopausal and perimenopausal women who are unwilling or unable to use bioidenticalhormone replacement therapy

  • Positive preganance test

  • Presence of an existing daignosis of non-Alzheimer's neurodegenerative disorderssuch as Lewy Body Disease, Frontotemporal Disease, Chronic Traumatic Encephalopathy,Korsakoff's Syndrome, etc.

  • A diagnosis of cerebrovascular disease as the primary cause of cognitive impairmentor early-stage dementia

  • Lack of adequate support from a study partner to assist with study adherence

  • Inability to exercise

  • Inabilty to use a computer with or without assistance; or no computer access

  • Plans to travel or be away from home for more than 2 weeks during the course of the 9-month study

  • Previous treatment using dietary changes, comprehensive nutritional support, ReCODEProgram, or similar methodology such as functional, integrative, or systems medicineat a level considered by the investigator to interfere with the study goals

  • Any contraindication to enclosed MRI

  • Unwilling or unable to comply with general study procedures

  • Current user of tobacco

  • Unwilling or unable to remediate or move away from identified sources of toxicities (molds, toxins, infections, dental decay)

  • Use of Aricept off-label

  • Two or more CNS-Vital Sign tests are invalid at baseline

Study Design

Total Participants: 72
Treatment Group(s): 4
Primary Treatment: Precision Medicine Approach
Phase: 3
Study Start date:
July 31, 2023
Estimated Completion Date:
April 30, 2026

Study Description

The precision medicine treatment approach to be evaluated in this clinical trial is a novel, functional, lifestyle intervention for the treatment of mild cognitive impairment or early-stage dementia. The protocol focuses on optimization of a diverse set of metabolic parameters coupled with lifestyle medicine and clinical nutrition strategies that address the mismatch in these contributors. The approach is personalized for each participant and based on more than 150 data points, including lab evaluations, brain scans, genomic evaluation, cognitive testing, and a detailed medical and family history. Importantly, this progressive treatment approach is based on continued optimization through iterative treatment and metabolic characterization.

The precision medicine treatment approach includes a core set of interventions (Precision Medicine-Core) and a set of interventions that are based on the clinical subtype of dementia (Precision Medicine-Cognitive Subtypes). All participants randomized to the precision medicine treatment approach group will receive the core treatment program. The elements of the core treatment program include diet, physical exercise, mental exercise, sleep optimization, and stress reduction.

In addition, all participants randomized to the precision medicine treatment approach will be evaluated for all putative or potential underlying drivers of dementia including:

  1. inflammatory factors (Type 1 Inflammatory), 2) glycotoxic factors (Type 1.5 Glycotoxic), 3) atrophic factors (Type 2 Atrophic), toxic factors (Type 3 Toxic), vascular factors (Type 4 Vascular), and traumatic factors (Type 5 Head Trauma).

This study will use a pragmatic, randomized, multicenter, control group design in which participants will be randomized to a 9-month precision medicine treatment approach or a 9-month standard-of-care treatment approach. Participants in the standard-of-care group will receive the standard-of-care mild cognitive impairment and early-stage dementia. Following completion of the 9-month intervention period, participants in the standard-of-care group will be eligible to receive the precision medicine treatment approach.

During the course of the 9-month precision medicine treatment approach, participants and study partners will be scheduled for regular visits with members of the study team at each practice. These visits will be scheduled at approximately 4-week intervals following randomization. Cognitive function tests will be performed at baseline (Visit 1), Month 3 (Visit 4), Month 6 (Visit 7), and Month 9 (Visit 10). Cognitive testing includes the MoCA to be performed by a blinded psychometrician prior to randomization and then 1-2 weeks before the 3-, 6-, and 9-month visits. The CNS Vital Signs will be performed by each staff at each of the six participating sites. Participants in the standard-of-care treatment group will complete a similar set of visits at the same intervals during this time.

A final follow-up visit will occur within 4 weeks of completion of Visit 10 to complete all effectiveness and safety follow-up assessments. Following completion of the final follow-up visit, all participants in the standard-of-care treatment group will be eligible for initiation of a 6-month precision medicine treatment approach. Safety data will be collected for participants in both groups through completion of the 6-month precision medicine intervention period for participants initially randomized to the standard-of-care treatment group. Periodic unblinded safety reviews are planned at approximately 1-month intervals for the full duration of the trial. These reviews will be conducted by the Study Oversight and Safety Review Committee.

Participants will be enrolled from six geographically-diverse clinical practices and randomized to either the precision medicine treatment approach (Group A) or the standard-of-care control group (Group B). The population to be enrolled will be heterogenous in terms of demographic and clinical characteristics of their cognitive dysfunctions. In addition, the precision medicine intervention will be heterogenous because, by definition, precision medicine is personalized to target the specific metabolic abnormalities that are identified in each participant as uniquely associated with mild cognitive impairment or early-stage dementia. Given the real-world settings, heterogeneity in study participants, and heterogeneity of the specific precision medicine components, a pragmatic, randomized, controlled trial will provide the best evaluation of the precision medicine treatment approach while offering maximum external validity and the ability to generalize findings from this study to precision medicine practice settings and patients who are treated in the US.

Connect with a study center

  • True Health Center for Functional Medicine

    Folsom, California 95630
    United States

    Site Not Available

  • Ann Hathaway, MD

    San Rafael, California 94903
    United States

    Site Not Available

  • Bay Area Wellness

    Walnut Creek, California 94597
    United States

    Site Not Available

  • Rezilir Health

    Hollywood, Florida 33020
    United States

    Site Not Available

  • Kemper Cognitive Wellness

    Rocky River, Ohio 44116
    United States

    Site Not Available

  • MaxWell Clinic, PLC

    Brentwood, Tennessee 37027
    United States

    Site Not Available

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