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| Name | Class |
|---|---|
| M.D. Anderson Cancer Center | OTHER |
| Massachusetts Institute of Technology | OTHER |
| Balchem Corporation | INDUSTRY |
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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.
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%.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Choline | Experimental | 2.2 g of choline, given as choline bitartrate, for a total of 180 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Choline | Drug | Eight 275mg capsules taken orally twice daily (4 capsules with breakfast & 4 capsules with dinner) x 180 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Changes in the fatty acid desaturation index (FADI) in the CSF following choline supplementation | 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 | FADI ( fatty acid desaturation index) will be utilized to determine whether saturated PC increases by 100% | baseline, 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with treatment-related adverse events | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Mini-Mental Status Examination (MMSE) following choline supplementation | 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 Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores following choline supplementation |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Paul E Schulz, MD | The University of Texas Health Science Center at Houston (UTHealth) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Texas Health Science Center at Houston (UTHealth) | Houston | Texas | 77054 | United States |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D002794 | Choline |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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Will compare scaled intensity between baseline and 6 months. |
| Baseline and 6 months |
| Changes in phosphatidylcholine in blood following choline supplementation | Aggregate values and percentages will be reported. | Baseline and 6 months |
| Changes in choline in blood following choline supplementation | Aggregate values and percentages will be reported | Baseline and 6 months |
| Changes in pTau181/Ab42 ratio in CSF following choline supplementation | 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 | 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 | 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 | 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 |
| Changes in neurofilament light chain (Nf-L) in CSF following choline supplementation | 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 | 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 | 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 |
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 |
| Change in Functional Activities Questionnaire (FAQ) scores following choline supplementation | 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 |
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D000588 |
| Amines |
| D050337 | Trimethyl Ammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D009861 | Onium Compounds |