Precision Medicine Approach for Early Dementia & Mild Cognitive Impairment

NCT05894954 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: EVANTHEA-2023
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Mild Cognitive Impairment; Dementia, Mild

Keywords

Mild Cognitive Impairment; Early-stage dementia; Mild dementia; Alzheimers Disease; Short term memory; Mental recall; MCI; Word finding difficulty

Outcome Measures

Primary Outcomes (2)

• Changes in mean Montreal Cognition Assessment (MoCA) scores over 9 months

  Compare changes over time between Group A and Group B in mean MoCA scores over 9 month treatment period

  Baseline and Months 3, 6, and 9 (end of study treatment)

• Changes in mean CNS Vital Signs Neurocognitive Index Scores over 9 months

  Compare changes over time in mean score on the CNS Vital Signs Neurocognitive Index over 9 month treatment period. Standard scores are used. 100 is the mean score with standard deviation of 15. No min/max value for the Index. Standard scores are normal distribution but there is a limit to human performance, towards 200. Higher score over time is better outcome.

  Baseline and Months 3, 6, and 9 (end of study treatment)

Secondary Outcomes (4)

• Changes over time in mean score on the Alzheimer's Questionnaire-21 (AQ-21) / Alzheimer's Questionnaire-20 (AQ-20)

  Baseline and Months 3, 6, and 9 (end of study treatment)

• Changes over time in mean score on the Patient-reported Outcome Measurement Information System (PROMIS-10).

  Baseline and Month 9 (end of study treatment)

• Discontinuation rates

  Throughout 9-month study treatment period

• Safety: Type, frequency, severity, relatedness, and expectedness of adverse events and serious adverse events.

  Throughout 9-month study treatment period

Other Outcomes (3)

• Changes over time in findings on volumetric magnetic resonance imaging (MRI).

  Baseline and Month 9 (end of study treatment)

• Change in serum biomarker, methylation epigenetics.

  Baseline and Month 9 (end of study treatment)

• Changes in serum biomarker, P-tau.

  Baseline and Month 9 (end of study treatment)

Study Arms (2)

Group A (Precision Medicine)

EXPERIMENTAL

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.

Dietary Supplement: Precision Medicine Approach; Combination Product: Hormones and Medications tailored to lab tests, combined with devices that support stress management and brain exercises; Behavioral: Lifestyle including diet, exercise, stress management

Group B (Standard-of-Care)

ACTIVE COMPARATOR

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

Behavioral: Standard-of-Care

Interventions

Precision Medicine Approach DIETARY_SUPPLEMENT

Precisions Medicine Approach involves a combination of medicines, dietary supplements, lifestyle changes, and diagnostics

Also known as: ReCODE

Group A (Precision Medicine)

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

Tailored Medications and Devices to address imbalances per lab results, known to affect cognitive function: Potential Devices: Oura Ring, Continuous Glucose Monitor, Keto-Mojo, and Heartmath Inner Balance. Few may receive Hyperbaric Oxygen Treatment, neurostimulation, neurofeedback, neurostimulation to reduce stress and relax the body), photobiomodulation (light therapy), or CPAP. Atrophic subtype support may include: estradiol, progesterone, testosterone, DHEA, pregnenolone, levothyroxine, liothyronine, hydrocortisone. Bacterial or Viral infection treatment may include: Doxycycline, Minocycline, Nitazoxanide, Hydroxychloroquine, Rifampin, Dapsone, Azithromycin, Tetracycline, Benzathine Penicillin G, Methylene Blue, Nystatin, Clotrimazole, Metronidazole, Valacyclovir, Acyclovir, Famciclovir, Shingles Vaccine Vascular treatments may include: antihypertensives, Ubrelvy, aspirin, Eliquis

Group A (Precision Medicine)

Standard-of-Care BEHAVIORAL

Participate in cognitively stimulating and social activities, exercise, sleep, control risk factors, adhere to a health diet, consult physician if conditions worsen

Also known as: Academy of Neurology practice guidelines

Group B (Standard-of-Care)

Lifestyle including diet, exercise, stress management BEHAVIORAL

Combining a tailored diet, exercise and stress management program supported by coaching specialists

Group A (Precision Medicine)

Eligibility Criteria

• Age: 45 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide signed informed consent
• Adults of any gender, race, or ethnicity and aged 45 to 76 years at time of enrollment
• Cognitive impairment or early-stage dementia as demonstrated by combination of AQ-21 score \>4 and either:
• MoCA 18-26, inclusive, or
• greater than or equal 2 scores in the bottom 50th percentilve for NCI or Executive Function, 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 all aspects of teh protocol and provide input for subjective ratings of the participant's cognitive status. The study partner must interact with teh participant frequently (live with or have daily contact with participant), and have sufficiently close relationship to observe and understand participant's difficulties with memor and 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 Android Smartphone or tablet capable of connecting to devices and applications used in the study
• Ability to use a computer and web interface, or have readily available assistance to facilitate the use of a computer and web interface
• Ability to converse with a coach or provider virtually to access the virtual coaching aspects of the treatment approach
• Willing and able to follow the protocol procesured and testing, including changes in diet, lifestyle, supplements, and medications
• Willing to have at least one home visit by the study health coach, including home evaluation for toxins or mold
• Willingness to remediate and/or move away from identifies sources of toxicity such as molds or other toxins or infections or dental decay
• Willingness to comply with COVID prevention precautions

You may not qualify if:

• Presence of any uncontrolled major medical illness, seizures, or cardiovascular disease
• Diagnosis of Type 1 Diabetes
• Presence of any major psychiatric diagnoses that impact the performance of activities of daily living or functioning, other than those related to cognitive decline
• Use of psychoactive medications known to impact cognition, unless willing and eligible to discontinue
• Use of chronic anticoagulation therapy, other than prophylactic aspirin or proteolytic enzymes, or a history of recurrent deep vein thrombosis
• MRI findings of hydrocephalus, focal stroke, extinsive white matter disease or brain tumor
• Prior traumatic brain injury of sufficient severity to impact functioning on a regular basis
• Diagnosis of cancer in past 5 years, or any history or breast cancer; exclusive of melanoma 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 bioidentical hormone replacement therapy
• Positive preganance test
• Presence of an existing daignosis of non-Alzheimer's neurodegenerative disorders such as Lewy Body Disease, Frontotemporal Disease, Chronic Traumatic Encephalopathy, Korsakoff's Syndrome, etc.
• A diagnosis of cerebrovascular disease as the primary cause of cognitive impairment or early-stage dementia
• Lack of adequate support from a study partner to assist with study adherence
• Inability to exercise

Sponsors & Collaborators

• Alzheimer's Prevention and Reversal Project, Inc.: lead
• Four Winds Foundation: collaborator

Study Sites (6)

True Health Center for Functional Medicine

Folsom, California, 95630, United States

Location

Ann Hathaway, MD

San Rafael, California, 94903, United States

Location

Bay Area Wellness

Walnut Creek, California, 94597, United States

Location

Rezilir Health

Hollywood, Florida, 33020, United States

Location

Kemper Cognitive Wellness

Rocky River, Ohio, 44116, United States

Location

MaxWell Clinic, PLC

Brentwood, Tennessee, 37027, United States

Location

Related Publications (7)

• Toups K, Hathaway A, Gordon D, Chung H, Raji C, Boyd A, Hill BD, Hausman-Cohen S, Attarha M, Chwa WJ, Jarrett M, Bredesen DE. Precision Medicine Approach to Alzheimer's Disease: Successful Pilot Project. J Alzheimers Dis. 2022;88(4):1411-1421. doi: 10.3233/JAD-215707.

  PMID: 35811518 BACKGROUND

• Bredesen DE, Amos EC, Canick J, Ackerley M, Raji C, Fiala M, Ahdidan J. Reversal of cognitive decline in Alzheimer's disease. Aging (Albany NY). 2016 Jun;8(6):1250-8. doi: 10.18632/aging.100981.

  PMID: 27294343 BACKGROUND

• Rao RV, Kumar S, Gregory J, Coward C, Okada S, Lipa W, Kelly L, Bredesen DE. ReCODE: A Personalized, Targeted, Multi-Factorial Therapeutic Program for Reversal of Cognitive Decline. Biomedicines. 2021 Sep 29;9(10):1348. doi: 10.3390/biomedicines9101348.

  PMID: 34680464 BACKGROUND

• Bredesen DE. Reversal of cognitive decline: a novel therapeutic program. Aging (Albany NY). 2014 Sep;6(9):707-17. doi: 10.18632/aging.100690.

  PMID: 25324467 BACKGROUND

• McMaster M, Kim S, Clare L, Torres SJ, D'Este C, Anstey KJ. Body, Brain, Life for Cognitive Decline (BBL-CD): protocol for a multidomain dementia risk reduction randomized controlled trial for subjective cognitive decline and mild cognitive impairment. Clin Interv Aging. 2018 Nov 21;13:2397-2406. doi: 10.2147/CIA.S182046. eCollection 2018.

  PMID: 30538436 BACKGROUND

• Ross MK, Raji C, Lokken KL, Bredesen DE, Roach JC, Funk CC, Price N, Rappaport N, Hood L, Heath JR. Case Study: A Precision Medicine Approach to Multifactorial Dementia and Alzheimer's Disease. J Alzheimers Dis Parkinsonism. 2021;11(Suppl 5):018. Epub 2021 Aug 25.

  PMID: 35237464 BACKGROUND

• Shetty P, Youngberg W. Clinical Lifestyle Medicine Strategies for Preventing and Reversing Memory Loss in Alzheimer's. Am J Lifestyle Med. 2018 May 11;12(5):391-395. doi: 10.1177/1559827618766468. eCollection 2018 Sep-Oct.

  PMID: 30283265 BACKGROUND

Related Links

• Published book describing basis for the precision medicine approach used in this trial

MeSH Terms

Conditions

Cognitive Dysfunction; Dementia; Lymphoma, Follicular; Alzheimer Disease; Anomia

Interventions

Hormones; Standard of Care; Exercise

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Tauopathies; Neurodegenerative Diseases; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Dale Bredesen, MD

  Alzheimer's Prevention and Reversal Project, Inc.

  STUDY CHAIR

• Kat Toups, MD

  Bay Area Wellness

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: A masked psychometrician will conduct the Montreal Cognitive Assessments (MoCA) and Alzheimers Questionnaires.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to one of two treatment groups. Group A is Precision Medicine Approach and Group B is the Standard-of-Care (Control) Group. Both groups will be on study for 9 months. Biomarker tests and cognition tests will be conducted in both groups at baseline, defined visits during the study and again at end of the 9-month period.

Study Record Dates

• First Submitted: April 30, 2023
• First Posted: June 8, 2023
• Study Start: July 31, 2023
• Primary Completion: October 31, 2025
• Study Completion: February 9, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)