Choline for Alzheimer's Disease

Overseen By Christine Farrell, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Paul E Schulz

Disqualifiers: TBI, Parkinson's, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether a dietary supplement called choline can slow down or prevent Alzheimer's disease in individuals at higher risk but not yet showing symptoms. Researchers are assessing choline's safety and how the body processes it over six months. Suitable participants have tested positive for a specific gene (ApoE4) linked to Alzheimer's risk and have normal cognitive function. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that moderate choline intake links to a lower risk of developing dementia, including Alzheimer's disease, suggesting potential benefits for brain health. Choline, a common dietary supplement, is already part of many diets and is generally well-tolerated by the body.

No specific reports of serious side effects have emerged from moderate choline levels. However, this trial aims to confirm the safety and tolerability of a higher dose over six months. As this study is in an early stage, researchers primarily focus on understanding the safety of this choline dosage in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Unlike the standard Alzheimer's treatments, which often focus on managing symptoms with medications like donepezil or memantine, choline targets a different mechanism entirely. Choline acts as a precursor to acetylcholine, a crucial neurotransmitter involved in memory and learning, which is typically depleted in Alzheimer's patients. Researchers are excited because this approach aims to address one of the root causes of cognitive decline rather than just alleviating symptoms. If effective, choline could offer a novel way to enhance brain function and slow the progression of Alzheimer's disease.

What evidence suggests that choline might be an effective treatment for Alzheimer's Disease?

Research has shown that choline, a nutrient found in many foods, is important for brain health and development. Some studies have found that people who consume more choline tend to perform better on memory and language tests. However, its direct effect on Alzheimer's disease (AD) in humans remains unclear. Although past research has not found a strong link between choline intake and improved cognitive skills in AD patients, some evidence suggests that choline might help maintain brain function. Additionally, animal studies have shown that choline supplements may reduce certain brain changes associated with AD. This trial will investigate the effects of choline supplementation on Alzheimer's, with participants receiving 2.2 g of choline as choline bitartrate for 180 days. Overall, more research is needed to confirm these effects in people at risk for Alzheimer's. ^{3 4 6 7 8}

Who Is on the Research Team?

Paul Schulz

Principal Investigator

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

Are You a Good Fit for This Trial?

This trial is for adults aged 55-80 who are at risk of Alzheimer's but not yet showing symptoms. They must have a certain gene variant (ApoE4), normal thinking skills, and good general health based on medical exams. Women should be post-menopausal or unable to bear children. People with other serious diseases, high choline diets, or unwillingness to undergo certain tests can't join.

Inclusion Criteria

Has signed an informed consent form before any assessment is performed as part of the study

Be able to understand the nature of the study and have the opportunity to have all questions answered

Has an MMSE score of 24 or greater (can be based on documented result obtained within the previous 3 months)

Exclusion Criteria

I cannot or do not want to have lumbar punctures.

I have had cancer in any part of my body in the last 5 years.

My health condition is stable and does not pose a risk to my safety in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2.2 g of choline bitartrate daily for 6 months to assess safety, tolerability, and biochemical effects

6 months

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Choline

Trial Overview The study is examining the safety and potential effects of choline—a dietary supplement—on individuals who are at increased risk for Alzheimer's Disease but do not yet show symptoms. The goal is to see if choline influences the progression towards Alzheimer's.

How Is the Trial Designed?

Group I: Choline Experimental Treatment 1 Intervention

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

Choline is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Choline for:

• Dietary supplement

Approved in European Union as Choline for:

• Dietary supplement

Approved in Canada as Choline for:

• Dietary supplement

Who Is Running the Clinical Trial?

Paul E Schulz

Lead Sponsor

Trials

2

Recruited

30+

Balchem Corporation

Industry Sponsor

Trials

4

Recruited

2,000+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

Massachusetts Institute of Technology

Collaborator

Trials

104

Recruited

12,810,000+

Balchem Corporation

Collaborator

Trials

3

Recruited

1,600+

Published Research Related to This Trial

In a one-month study involving patients with Alzheimer's disease, a daily dose of 1000 mg of CDP-choline led to slight improvements in mental performance and changes in brain activity, such as increased alpha power in the occipital areas.

CDP-choline also enhanced blood flow to the brain and reduced levels of inflammatory markers like histamine and interleukin-1, suggesting potential benefits in cerebrovascular health and inflammation management in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effects of CDP-choline in Alzheimer's disease. Cognition, brain mapping, cerebrovascular hemodynamics, and immune factors. Cacabelos, R., Caamaño, J., Gómez, MJ., et al.[2019]

In a study involving 11 outpatients with moderate Alzheimer's disease, lecithin supplementation significantly increased plasma choline levels threefold during treatment.

Despite the increase in choline levels, there were no significant differences in psychological test scores between the lecithin and placebo groups, suggesting that lecithin may not have a meaningful impact on cognitive function in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alzheimer disease: lack of effect of lecithin treatment for 3 months. Etienne, P., Dastoor, D., Gauthier, S., et al.[2019]

Tacrine, a cholinesterase inhibitor, has been shown to improve cognition and overall status in Alzheimer's patients, with its effects confirmed through multiple clinical trials involving different study designs.

The effectiveness of tacrine is dose-dependent, with a linear response observed at dosages ranging from 40 to 160 mg per day, and about one-third of patients show a significantly greater response compared to others.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of tacrine and lecithin in Alzheimer's disease. A population pharmacodynamic analysis of five clinical trials. Holford, NH., Peace, K.[2019]

In a double-blind crossover study involving seven patients with mild to moderate Alzheimer's disease, treatment with choline chloride at various doses did not result in significant overall improvement in cognitive function.

Despite increasing plasma choline levels more than twofold, none of the doses (50, 100, or 200 mg/kg/24 hrs) showed efficacy in enhancing the patients' condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Choline chloride fails to improve cognition of Alzheimer's disease. Thal, LJ., Rosen, W., Sharpless, NS., et al.[2019]

Patients with Alzheimer's disease (AD) have significantly higher levels of red blood cell choline compared to normal elderly controls, suggesting a potential biomarker for the disease.

In contrast, red blood cell lipid-bound choline levels are significantly lower in AD patients, indicating possible alterations in phospholipid metabolism associated with Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in red blood cell choline and lipid-bound choline between patients with Alzheimer disease and control subjects. Miller, BL., Read, S., Tang, C., et al.[2019]

Acetylcholinesterase inhibitors (AChEIs) like donepezil, galantamine, and rivastigmine provide modest improvements in cognition, function, and behavior for patients with Alzheimer's disease, based on numerous clinical trials and post-marketing studies.

While AChEIs are generally associated with mild adverse events, careful consideration of their safety profiles, drug interactions, and the potential for worsening cognitive impairment upon discontinuation is crucial for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acetylcholinesterase inhibitors for treating dementia symptoms - a safety evaluation. Mohammad, D., Chan, P., Bradley, J., et al.[2022]

Tetrahydroaminoacridine (THA) combined with highly concentrated lecithin showed promising improvements in cognition and functional autonomy in Alzheimer's patients, as measured by the Mini Mental State and Rapid Disability Rating Scale-2.

Current studies are underway to further evaluate the efficacy of this combination treatment through double-blind cross-over trials, indicating a structured approach to testing new therapies for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress report on the Canadian Multicentre Trial of tetrahydroaminoacridine with lecithin in Alzheimer's disease. Gauthier, S., Bouchard, R., Bacher, Y., et al.[2019]

Alzheimer's brain tissue shows a decreased ability to release choline from lecithin and phosphorylcholine, indicating a potential metabolic issue related to choline processing.

This reduction suggests that dietary supplements containing choline or lecithin may not be effective in treating or managing Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phosphatase and phospholipase activity in Alzheimer brain tissues. Kanfer, JN., McCartney, DG.[2016]

In a rat model of Alzheimer's disease, unilateral lesion of the cholinergic nucleus basalis led to significant decreases in choline acetyltransferase activity and membrane phospholipid levels in the frontal cortex, indicating impaired cholinergic transmission affects phospholipid metabolism.

The study found that after the lesion, there was an increase in muscarinic receptor sensitivity, suggesting that the cholinergic system's dysfunction may lead to altered phospholipid hydrolysis in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phospholipid and phospholipid metabolites in rat frontal cortex are decreased following nucleus basalis lesions. Holmes, TC., Nitsch, RM., Erfurth, A., et al.[2019]

In a study involving patients with early-onset and late-onset Alzheimer's disease, treatment with CDP-choline significantly reduced blood levels of histamine by two-fold over 30 days, indicating its potential as an immunomodulator.

The reduction in histamine levels was observed as early as 2 hours after administration, suggesting that CDP-choline may help address the hyperactivation of the histaminergic system associated with Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDP-choline-induced blood histamine changes in Alzheimer's disease. Fernández-Novoa, L., Alvarez, XA., Franco-Maside, A., et al.[2013]

Anticholinesterase drugs, such as donepezil and rivastigmine, provide significant cognitive benefits for patients with mild-to-moderate Alzheimer's disease, although they can cause side effects in 5% to 15% of cases, including nausea and dizziness.

Memantine, an NMDA receptor antagonist, offers an alternative treatment for moderately severe to severe Alzheimer's disease by protecting neurons from harmful glutamate activity while supporting normal neurotransmitter function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of cognitive impairment in Alzheimer's disease. Burns, A.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10493398/

Association between choline supplementation and ... Some studies report no relationship between choline intake and cognitive function or improvement in Alzheimer's disease patients.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2405457724013287

Unlocking choline's potential in Alzheimer's disease Choline, an essential dietary nutrient plays a critical role in neurological development and brain function, however, its effects on AD in humans is unclear.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05880849

NCT05880849 | Choline Effects - Pre-symptomatic 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 ...

4. ajcn.nutrition.org ajcn.nutrition.org/article/S0002-9165(22)01320-X/fulltext

Choline and phosphatidylcholine may maintain cognitive ... Dietary intakes of choline and phosphatidylcholine were associated with better performance in cognitive tests assessing verbal fluency and memory.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12482226/

The association of dietary choline intakes with cognitive ... Maternal choline supplementation ameliorates Alzheimer's disease pathology by reducing brain homocysteine levels across multiple generations.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9630864/

Is dietary choline intake related to dementia and ... Low intake of dietary choline was associated with increased risks of dementia and AD, compared to medium intake. High intake was associated with increased risks ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002916524008694

Association of dietary choline intake with incidence ... Our findings suggest that moderate dietary choline intake, ranging from 332.89 mg/d to 353.93 mg/d, is associated with lower odds of dementia and better ...

8. ajcn.nutrition.org ajcn.nutrition.org/article/S0002-9165(24)00869-4/abstract

Association of dietary choline intake with incidence of ... Participants in the 2nd quartile of total choline intake had lower risks than those in the lowest quartile, with HR of 0.80 (95% CI: 0.67, 0.96) for dementia ...