Mild Cognitive ImpairmentPhase 3EVANTHEANCT05894954
Precision Medicine Approach for Early Dementia & Mild Cognitive Impairment
A Phase 3 study testing Precision Medicine Approach, Hormones and Medications tailored to lab tests, combined with devices that support stress management and brain exercises and Standard-of-Care in people with Mild Cognitive Impairment and Dementia, Mild, run by Alzheimer's Prevention and Reversal Project, Inc. at 6 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 45 to 76 years
- Conditions the study is for
- Mild Cognitive Impairment, Dementia, Mild
- What is being tested?
- Precision Medicine Approach, Hormones and Medications tailored to lab tests, combined with devices that support stress management and brain exercises and Standard-of-Care
- Type of treatment
- Vaccines, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 73 participants
- Where
- 6 sitesUnited States
- Study dates
- 31 Jul 2023to 9 Feb 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 76 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Participants taking Aricept will be considered if they have been using Aricept for at 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 the course of the study.
- Women who are premenopausal and sexually active must be willing to use appropriate contraception 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 health issues detected during these screening exams: 1) Mammogram within 12 months of randomization; 2) Pelvic exam within 12 moths for women less than 60 years or pelvic exam within 24 months if 60 years or older.
Who cannot join
- 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
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- 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
- 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, ReCODE Program, or similar methodology such as functional, integrative, or systems medicine at 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
MaxWell Clinic, PLC
Brentwood, Tennessee, 37027
True Health Center for Functional Medicine
Folsom, California, 95630
Rezilir Health
Hollywood, Florida, 33020
Kemper Cognitive Wellness
Rocky River, Ohio, 44116
Ann Hathaway, MD
San Rafael, California, 94903
Bay Area Wellness
Walnut Creek, California, 94597
About this study
Official title: EVANTHEA TRIAL: A Pragmatic, Randomized, Controlled Trial to Evaluate the Effectiveness of a Precision Medicine Treatment Approach for Early Dementia and Mild Cognitive Impairment
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:
Read more
- 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.
Read the detailed 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.
- Conditions
- Mild Cognitive Impairment, Dementia, Mild
- Being tested
- Precision Medicine Approach, Hormones and Medications tailored to lab tests, combined with devices that support stress management and brain exercises, Standard-of-Care, Lifestyle including diet, exercise, stress management
- Keywords
- Mild Cognitive Impairment, Early-stage dementia, Mild dementia, Alzheimers Disease, Short term memory, Mental recall, MCI, Word finding difficulty
- Medical subject headings
- Cognitive Dysfunction, Dementia, Lymphoma, Follicular, Alzheimer Disease, Anomia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Precision Medicine ApproachDietary supplement
Also called ReCODE
Precisions Medicine Approach involves a combination of medicines, dietary supplements, lifestyle changes, and diagnostics
Hormones and Medications tailored to lab tests, combined with devices that support stress management and brain exercisesCombination 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
Standard-of-CareBehavioural
Also called Academy of Neurology practice guidelines
Participate in cognitively stimulating and social activities, exercise, sleep, control risk factors, adhere to a health diet, consult physician if conditions worsen
Lifestyle including diet, exercise, stress managementBehavioural
Combining a tailored diet, exercise and stress management program supported by coaching specialists
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Behavioral: Standard-of-Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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)
Compare changes over time between Group A and Group B in mean Alzheimer's Questionnaire scores. AQ-21 is baseline; AQ-20 is a modified version of the AQ-21 to address changes from baseline. The AQ© total score is based on the sum of points for items with a yes response. The range of possible scores is 0 to 27. Score interpretation: A score of four points or less is regarded as normal. A score between five and 14 points inclusive suggests mild cognitive impairment. A score of 15 or more points suggests dementia. Lower score over time is a better outcome.
Measured: 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).
Evaluate Group A treatment compared with Group B treatment with regard to changes over time in mean PROMIS-10 score. The PROMIS Global-10 is a 10-item patient-reported questionnaire in which the response options are presented as 5-point (as well as a single 11-point) rating scales. The results of the questions are used to calculate two summary scores: a Global Physical Health Score and a Global Mental Health score. The possible score ranges from 0 to 20 points in each case. 0 points represent the patient's most severe physical and/or mental impairment, while 20 points represent the best possible state of health.
Measured: Baseline and Month 9 (end of study treatment)
Discontinuation rates
Evaluate acceptability of the precision medicine intervention approach by comparing discontinuation rates in Group A and Group B participants
Measured: Throughout 9-month study treatment period
Safety: Type, frequency, severity, relatedness, and expectedness of adverse events and serious adverse events.
Determine the safety of the Group A treatment compared with Group B treatment based on the type, frequency, severity, relatedness, and expectedness of adverse events and serious adverse events.
Measured: Throughout 9-month study treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2023
- Study start31 Jul 2023
- Primary completion31 Oct 2025
- Study completion9 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alzheimer's Prevention and Reversal Project, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Four Winds Foundation
- Responsible party
- Sponsor
- Investigators
- Dale Bredesen, MD, Study chair, Alzheimer's Prevention and Reversal Project, Inc.Kat Toups, MD, Principal investigator, Bay Area Wellness
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05894954
- Sponsor's protocol ID
- EVANTHEA-2023
- Acronym
- EVANTHEA
- Status last verified
- Feb 2026
- First submitted
- 30 Apr 2023
- Last updated
- 18 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35811518Bredesen 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.
PubMed 27294343Rao 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.
PubMed 34680464Bredesen DE. Reversal of cognitive decline: a novel therapeutic program. Aging (Albany NY). 2014 Sep;6(9):707-17. doi: 10.18632/aging.100690.
PubMed 25324467McMaster 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.
PubMed 30538436Ross 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.
PubMed 35237464Shetty 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.
PubMed 30283265
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- EVANTHEA TRIAL: A Pragmatic, Randomized, Controlled Trial to Evaluate the Effectiveness of a Precision Medicine Treatment Approach for Early Dementia and Mild Cognitive Impairment
- ClinicalTrials.gov ID
- NCT05894954
- Acronym / sponsor ID
- EVANTHEA / EVANTHEA-2023
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- Alzheimer's Prevention and Reversal Project, Inc.University, hospital or other
- Collaborators
- Four Winds Foundation
- Study start
- 31 Jul 2023 (actual)
- Primary completion
- 31 Oct 2025 (actual)
- Study completion
- 9 Feb 2026 (actual)
- First posted
- 8 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Group A (Precision Medicine) | Experimental | 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 managementPrecision 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 B (Standard-of-Care) | Active comparator | Behavioral: Standard-of-CareStandard-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 |
Who may qualify
- Ages
- 45 to 76 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Precision Medicine ApproachAlso: ReCODEPrecisions Medicine Approach involves a combination of medicines, dietary supplements, lifestyle changes, and diagnostics | Dietary supplement | Group A (Precision Medicine) |
| Hormones and Medications tailored to lab tests, combined with devices that support stress management and brain exercisesTailored 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 | Combination product | Group A (Precision Medicine) |
| Standard-of-CareAlso: Academy of Neurology practice guidelinesParticipate in cognitively stimulating and social activities, exercise, sleep, control risk factors, adhere to a health diet, consult physician if conditions worsen | Behavioural | Group B (Standard-of-Care) |
| Lifestyle including diet, exercise, stress managementCombining a tailored diet, exercise and stress management program supported by coaching specialists | Behavioural | Group A (Precision Medicine) |
Primary outcome
Changes in mean Montreal Cognition Assessment (MoCA) scores over 9 months
Time frame: Baseline and Months 3, 6, and 9 (end of study treatment)
Compare changes over time between Group A and Group B in mean MoCA scores over 9 month treatment period
Changes in mean CNS Vital Signs Neurocognitive Index Scores over 9 months
Time frame: Baseline and Months 3, 6, and 9 (end of study treatment)
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.
4 secondary outcomes
Changes over time in mean score on the Alzheimer's Questionnaire-21 (AQ-21) / Alzheimer's Questionnaire-20 (AQ-20)
Time frame: 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).
Time frame: Baseline and Month 9 (end of study treatment)
Discontinuation rates
Time frame: Throughout 9-month study treatment period
Safety: Type, frequency, severity, relatedness, and expectedness of adverse events and serious adverse events.
Time frame: Throughout 9-month study treatment period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2026.
- Background: PubMed 35811518Toups 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.
- Background: PubMed 27294343Bredesen 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.
- Background: PubMed 34680464Rao 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.
- Background: PubMed 25324467Bredesen DE. Reversal of cognitive decline: a novel therapeutic program. Aging (Albany NY). 2014 Sep;6(9):707-17. doi: 10.18632/aging.100690.
- Background: PubMed 30538436McMaster 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.
- Background: PubMed 35237464Ross 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.
- Background: PubMed 30283265Shetty 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.
- Published book describing basis for the precision medicine approach used in this trialLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dale Bredesen, MD study chair
Alzheimer's Prevention and Reversal Project, Inc.
Kat Toups, MD principal investigator
Bay Area Wellness
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Precision Medicine Approach, Hormones and Medications tailored to lab tests, combined with devices that support stress management and brain exercises and Standard-of-Care in people with Mild Cognitive Impairment and Dementia, Mild, run by Alzheimer's Prevention and Reversal Project, Inc. at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in mean Montreal Cognition Assessment (MoCA) scores over 9 months (time frame: Baseline and Months 3, 6, and 9 (end of study treatment)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05894954, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2026.