Choline Effects - Pre-symptomatic AD

NCT ID: NCT05880849

Last Updated: 2025-10-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-26
• Study Completion Date: 2026-11-30

Brief Summary

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.

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%.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Choline

2.2 g of choline, given as choline bitartrate, for a total of 180 days.

Group Type: EXPERIMENTAL

Choline

Intervention Type: DRUG

Eight 275mg capsules taken orally twice daily (4 capsules with breakfast \& 4 capsules with dinner) x 180 days

Interventions

Choline

Eight 275mg capsules taken orally twice daily (4 capsules with breakfast \& 4 capsules with dinner) x 180 days

Intervention Type: DRUG

Other Intervention Names

Choline Bitartrate; VitaCholine(R)

Eligibility Criteria

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.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

M.D. Anderson Cancer Center

OTHER

Sponsor Role: collaborator

Massachusetts Institute of Technology

OTHER

Sponsor Role: collaborator

Balchem Corporation

INDUSTRY

Sponsor Role: collaborator

Paul E Schulz

OTHER

Sponsor Role: lead

Responsible Party

Paul E Schulz

Professor, Department of Neurology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Paul E Schulz, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center at Houston (UTHealth)

Locations

The University of Texas Health Science Center at Houston (UTHealth)

Houston, Texas, United States

Countries

United States

Other Identifiers

HSC-MS-22-0637

Identifier Type: -

Identifier Source: org_study_id