A Phase 3 interventional study of Precision Medicine Approach and Hormones and Medications tailored to lab tests, combined with devices that support stress management and brain exercises in Mild Cognitive Impairment and Dementia, Mild, sponsored by Alzheimer's Prevention and Reversal Project, Inc.. Completed at 6 sites in United States. Open to participants aged 45 Years to 76 Years. Per ClinicalTrials.gov, last updated 2026-02-18.
Sponsored by Alzheimer's Prevention and Reversal Project, Inc. · Phase 3, Interventional, and Treatment
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:
Participants will be asked to:
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.
3,872 studies on the registry are indexed under Cognitive Dysfunction; 1,119 are open to participants now.
This study's enrollment of 73 is above the median of 64 across 2,794 interventional studies indexed under Cognitive Dysfunction.
Browse Cognitive Dysfunction studies →This is the only study on the registry with Alzheimer's Prevention and Reversal Project, Inc. as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
Precisions Medicine Approach involves a combination of medicines, dietary supplements, lifestyle changes, and diagnostics
Also known as: ReCODE
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
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
Combining a tailored diet, exercise and stress management program supported by coaching specialists
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
Time frame: 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.
Time frame: Baseline and Months 3, 6, and 9 (end of study treatment)
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.
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).
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.
Time frame: 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
Time frame: 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.
Time frame: Throughout 9-month study treatment period
Changes over time in findings on volumetric magnetic resonance imaging (MRI).
Compare the impact of a Group A treatment approach with Group B treatment in regards to changes over time in findings on volumetric magnetic resonance imaging (MRI).
Time frame: Baseline and Month 9 (end of study treatment)
Change in serum biomarker, methylation epigenetics.
Compare changes in methylation epigenetic results between Group A and Group B participants at the same timepoints, beginning and end of treatment.
Time frame: Baseline and Month 9 (end of study treatment)
Changes in serum biomarker, P-tau.
Compare changes P-tau results between Group A and Group B participants at the same timepoints, beginning and end of treatment. Lowering of P-Tau over course of the study is positive outcome.
Time frame: Baseline and Month 9 (end of study treatment)
Plan to share: No
Ran from Jul 2023 to primary completion in Oct 2025, 27 months.
Of 49 phase 3 interventional studies under Cognitive Dysfunction, half reached primary completion within 44 months of starting (the median), counting those still running; a quarter within 33 and three quarters within 63. This study's 27 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Feb 2026. You cannot join it, but the record below documents what was studied.
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