Clinical trial NCT05880849: Choline Effects - Pre-symptomatic AD
Official title: Testing Whether Choline Normalizes Lipid Metabolism in APOE4 Carriers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Alzheimer Disease
Keywords: pre-symptomatic AD
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
Collaborators: name: M.D. Anderson Cancer Center
name: Massachusetts Institute of Technology
name: Balchem Corporation
First posted: 2023-05-30
Enrollment: 14
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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%.

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.

Primary outcomes:
measure: Changes in the fatty acid desaturation index (FADI) in the CSF following choline supplementation
timeFrame: baseline, 6 months
measure: Changes in phosphatidylcholine (PC) in the CSF following choline supplementation
timeFrame: baseline, 6 months
Secondary outcomes:
measure: Number of participants with treatment-related adverse events
timeFrame: 9 months
measure: Changes in phospholipids in CSF following choline supplementation
timeFrame: Baseline and 6 months
measure: Changes in phosphatidylcholine in blood following choline supplementation
timeFrame: Baseline and 6 months
measure: Changes in choline in blood following choline supplementation
timeFrame: Baseline and 6 months
measure: Changes in proinflammatory cytokines in blood plasma following choline supplementation
timeFrame: Baseline and 6 months
measure: Changes in neurofilament light chain (Nf-L) in CSF following choline supplementation
timeFrame: Baseline and 6 months
measure: Changes in amyloid-β 42/40 ratio CSF following choline supplementation
timeFrame: Baseline and 6 months
measure: Changes in p-Tau/Total Tau ratio in CSF following choline supplementation
timeFrame: Baseline and 6 months
Other outcomes:
measure: Change in Mini-Mental Status Examination (MMSE) following choline supplementation
timeFrame: Baseline and 6 months
measure: Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores following choline supplementation
timeFrame: Baseline and 6 months
measure: Change in Functional Activities Questionnaire (FAQ) scores following choline supplementation
timeFrame: Baseline and 6 months
Locations:
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston (UTHealth)
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at Houston (UTHealth)
name: Paul E Schulz, MD
role: PRINCIPAL_INVESTIGATOR
References: