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

14 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests if choline bitartrate, a dietary supplement, can help people at risk of Alzheimer's Disease. The supplement aims to improve how brain cells handle fats, potentially keeping them healthy and functioning properly.

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 choline safe for humans?

Choline, in the form of CDP-choline, has been used in studies with Alzheimer's patients at doses of 1000 mg per day for a month without major safety concerns. However, it can affect blood histamine levels, which might influence immune function. ^{1 2 3 4 5}

How is the drug choline different from other Alzheimer's treatments?

Choline, as a treatment for Alzheimer's, is unique because it targets phospholipid metabolism, which is altered in Alzheimer's patients. However, studies have shown that choline supplements do not significantly improve cognitive function in Alzheimer's patients, suggesting it may not be effective as a standalone treatment. ^{1 3 6 7 8}

What evidence supports the effectiveness of the drug choline for Alzheimer's disease?

Research shows that lecithin, a choline precursor, has a small additional benefit on cognitive status in Alzheimer's patients when used with tacrine, a different Alzheimer's drug. However, other studies found no significant improvement in Alzheimer's symptoms with choline or lecithin alone. ^{1 6 9 10 11}

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

I am between 55 and 80 years old.

Is in the opinion of the Investigator, in good general medical health based upon medical history, physical examination, laboratory tests, vital signs and EKG

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Alzheimer disease: lack of effect of lecithin treatment for 3 months. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Therapeutic effects of CDP-choline in Alzheimer's disease. Cognition, brain mapping, cerebrovascular hemodynamics, and immune factors. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Progress report on the Canadian Multicentre Trial of tetrahydroaminoacridine with lecithin in Alzheimer's disease. [2019]

4. Austria pubmed.ncbi.nlm.nih.gov

Phosphatase and phospholipase activity in Alzheimer brain tissues. [2016]

5. Germany pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Acetylcholinesterase inhibitors for treating dementia symptoms - a safety evaluation. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Choline chloride fails to improve cognition of Alzheimer's disease. [2019]

8. Spain pubmed.ncbi.nlm.nih.gov

CDP-choline-induced blood histamine changes in Alzheimer's disease. [2013]

9. England pubmed.ncbi.nlm.nih.gov

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

10. United States pubmed.ncbi.nlm.nih.gov

Differences in red blood cell choline and lipid-bound choline between patients with Alzheimer disease and control subjects. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Phospholipid and phospholipid metabolites in rat frontal cortex are decreased following nucleus basalis lesions. [2019]