NCT05880849

Choline Effects - Pre-symptomatic AD

Testing Whether Choline Normalizes Lipid Metabolism in APOE4 Carriers

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: Paul E Schulz · Academic / Other
• Sex: All
• Age: 55 Years – 80 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	Choline	Eight 275mg capsules taken orally twice daily (4 capsules with breakfast \& 4 capsules with dinner) x 180 days

Timeline

• Start date: 2023-06-26
• Primary completion: 2025-07-01
• Completion: 2025-10-10
• First posted: 2023-05-30
• Last updated: 2026-02-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study