Choline Effects - Pre-symptomatic AD

April 16, 2026 updated by: Paul E Schulz

Testing Whether Choline Normalizes Lipid Metabolism in APOE4 Carriers

The purpose of this study is to test the safety, tolerability, and effects of choline in people with increased risk of Alzheimer's Disease (AD), also known as pre-symptomatic AD. Choline is a dietary supplement, but is being investigated to see if it has any effects on the progression to AD.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The purpose of this study is to determine the safety and tolerability, as well as the biochemical effects of choline bitartrate over a 6-month treatment period in a moderately sized population harboring at least one copy of the APOE4 gene. APOE is a protein involved in lipid transport. Studies show that the APOE4 variant is strongly associated with an increased risk of Alzheimer's Disease. It is unclear how APOE4 results in an increased risk for AD, but a recent study identified a novel molecular pathway, which showed that APOE4-induced dysfunction of lipid metabolism in neurons by cellular accumulation of unsaturated lipids. The investigators hypothesize that choline supplementation normalizes the APOE4-mediated dysregulation by normalizing the Kennedy pathway in neuronal cells, thus stabilizing the lipid metabolism and concomitantly restoring normal cell function by increasing phosphatidylcholine activity via the Kennedy pathway. To evaluate this, the investigators will test if choline supplementation will decrease the ratio of unsaturated lipids to saturated lipids (the fatty acid desaturation index) in cerebrospinal fluid by 15% and increase phosphatidylcholine by 100%.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77054
        • The University of Texas Health Science Center at Houston (UTHealth)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Has signed an informed consent form before any assessment is performed as part of the study.
  2. Be male or female between 55 and 80 years old.
  3. Be able to understand the nature of the study and have the opportunity to have all questions answered.
  4. Has tested positive for at least one copy of ApoE4.
  5. Has an MMSE score of 24 or greater. (can be based on documented result obtained within the previous 3 months).
  6. Is in the opinion of the Investigator, in good general medical health based upon medical history, physical examination, laboratory tests, vital signs and EKG.
  7. Has normal levels of Homocysteine in blood tests. A normal blood level is between 5 to 15 micromoles (mcmol/L)
  8. Completes the dietary interview with dietician.
  9. Females must be considered post-menopausal or not of child bearing potential.

Exclusion Criteria:

  1. Current medical or neurological condition that might impact cognition or performance on cognitive assessments. (e.g. TBI, Parkinson's disease, multiple sclerosis, etc.)
  2. Inability or unwillingness of patient to undergo neuropsychological testing.
  3. Advanced, severe progressive or unstable disease that may interfere with the safety, tolerability and study assessments, or put the participant at special risk. (e.g. significant cardiac disease, severe renal impairment, severe hepatic impairment etc.)
  4. History of malignancy of any organ system, treated or untreated, within the past 60 months.
  5. Inability or unwillingness to undergo Lumbar Punctures.
  6. High dietary choline intake (more than 450mg) as determined by dietician
  7. Any condition, which in the opinion of the investigator, would put the subject at undue risk or would interfere with evaluation of the investigational product or interpretation of subject safety or study results.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Choline
2.2 g of choline, given as choline bitartrate, for a total of 180 days.
Drug: Choline
Eight 275mg capsules taken orally twice daily (4 capsules with breakfast & 4 capsules with dinner) x 180 days
Other Names:
  • Choline Bitartrate
  • VitaCholine(R)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes in the fatty acid desaturation index (FADI) in the CSF following choline supplementation
Time Frame: baseline, 6 months
FADI will be utilized to determine whether unsaturated to saturated lipids decreases by 15%
baseline, 6 months
Changes in phosphatidylcholine (PC) in the CSF following choline supplementation
Time Frame: baseline, 6 months
FADI ( fatty acid desaturation index) will be utilized to determine whether saturated PC increases by 100%
baseline, 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-related adverse events
Time Frame: 9 months
Safety endpoints will be monitored throughout the study and number of incidents reported at end of study. Aggregate values and percentages will be reported
9 months
Changes in phospholipids in CSF following choline supplementation
Time Frame: Baseline and 6 months
Will compare scaled intensity between baseline and 6 months.
Baseline and 6 months
Changes in phosphatidylcholine in blood following choline supplementation
Time Frame: Baseline and 6 months
Aggregate values and percentages will be reported.
Baseline and 6 months
Changes in choline in blood following choline supplementation
Time Frame: Baseline and 6 months
Aggregate values and percentages will be reported
Baseline and 6 months
Changes in neurofilament light chain (Nf-L) in CSF following choline supplementation
Time Frame: Baseline and 6 months
Levels of NfL in CSF will be measured using commercially available immunosorbent assays to determine potential treatment effects. Aggregate values and percentages will be reported. Each sample will be tested in triplicate.
Baseline and 6 months
Changes in amyloid-β 42/40 ratio CSF following choline supplementation
Time Frame: Baseline and 6 months
Levels of amyloid-β 42/40 ratio in CSF will be measured by LC/MS/MS assays. Aggregate values and percentages will be reported.
Baseline and 6 months
Changes in p-Tau/Total Tau ratio in CSF following choline supplementation
Time Frame: Baseline and 6 months
Levels of p-Tau/Total Tau will be measured by LC/MS/MS assays. Aggregate values and percentages will be reported.
Baseline and 6 months
Changes in pTau181/Ab42 ratio in CSF following choline supplementation
Time Frame: Baseline and 6 months
Levels of pTau181 and Ab42 in CSF will be measured using commercially available immunosorbent assays to determine potential treatment effects. Ratios will be reported.
Baseline and 6 months
Changes in pTau217 in plasma following choline supplementation
Time Frame: Baseline and 6 months
Levels of pTau217 in plasma will be measured using commercially available immunosorbent assays to determine potential treatment effects. Fold change will be reported.
Baseline and 6 months
Changes in betaine in plasma following choline supplementation
Time Frame: Baseline and 6 months
Levels of betaine in plasma will be measured using LC/MS/MS to determine potential treatment effects. Fold changes will be reported.
Baseline and 6 months
Changes in betaine in CSF following choline supplementation
Time Frame: Baseline and 6 months
Levels of betaine in CSF will be measured using LC/MS/MS to determine potential treatment effects. Fold changes will be reported.
Baseline and 6 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Mini-Mental Status Examination (MMSE) following choline supplementation
Time Frame: Baseline and 6 months
Cognition measured by MMSE. Scoring: 24-30 no cognitive impairment; 18-23 mild cognitive impairment; 0-17 severe cognitive impairment.
Baseline and 6 months
Change in Functional Activities Questionnaire (FAQ) scores following choline supplementation
Time Frame: Baseline and 6 months
Measure instrumental activities of daily living (IADLs) by FAQ. Sum scores (range 1-30). Cut-point of 9 (dependent in 3 or more activities) is recommended to indicate impaired function and possible cognitive impairment.
Baseline and 6 months
Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores following choline supplementation
Time Frame: Baseline and 6 months
Cognitive decline measured by RBANS. Total Score subtest ranges: List Learning (0-40); Story Memory (0-24); Figure Copy (0-20); Line Orientation (0-20); Picture Naming (0-10); Semantic Fluency (4-40); Digit Span (0-16); Coding (0-89); List Recall (0-10); List Recognition (0-20); Story Recall (0-12); Figure Recall (0-20). Use Stimulus Booklet to convert Total Scores to Index Scores and Sum of Index Scores to Total Scale. Total Scores can range from 40 to 160. The RBANS scores are displayed as standard scores with means of 100 and a standard deviation of 15. Average/Mild Impairment (standard scores of 70 or above), Moderate Impairment (standard scores from 55 to 69), and Severe Impairment (standard scores <54).
Baseline and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Paul E Schulz

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
M.D. Anderson Cancer Center
Massachusetts Institute of Technology
Balchem Corporation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Paul E Schulz, MD, The University of Texas Health Science Center at Houston (UTHealth)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 26, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 10, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 10, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 25, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 30, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 16, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HSC-MS-22-0637

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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