Equol for Cognitive Impairment

(ACE Trial)

Recruiting at 2 trial locations

Overseen By Monica Love, MLIS

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Akira Sekikawa

Must not be taking: Isoflavone supplements, Estrogen therapy

Disqualifiers: Stroke, Neurological disorders, Bipolar, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 24 months

372 Participants Needed

Trial Summary

What is the purpose of this trial?

The ACE Trial, funded by the National Institute on Ageing/National Institutes of Health (NIH), is a multicenter clinical trial. The ACE Trial will determine if taking the dietary supplement Equol could slow the progression of stiffening of the arteries, small blood vessel disease in the brain and memory decline. Equol is a soy-based supplement that has plant estrogen-like compounds in it. Equol is a metabolite of soy isoflavone. Our studies in Japan and other studies suggest that Equol may slow mechanisms related to memory decline. No previous studies in the United States have tested the effect of Equol on these mechanisms or memory decline. Supplementation of Equol in the ACE Trial is approved by the Food and Drug Administration (FDA). Researchers at the University of Pittsburgh, Pittsburgh, Pennsylvania, Wake Forest University, Winston-Salem, North Carolina, and Emory University, Atlanta, Georgia, are recruiting participants. The ACE Trial will ask participants to complete 7 clinic visits over a two-year period. The participants are asked to take Equol tablets daily for 24 months. Clinic procedures include Pulse Wave Velocity (to measure arterial stiffness), Magnetic Resonance Imaging (MRI) of the brain and tests of awareness and thinking.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take isoflavone supplements or eat soy products more than twice a week. If you are on estrogen replacement therapy, you cannot participate in the trial.

What data supports the effectiveness of the treatment Equol for cognitive impairment?

While there is no direct evidence for Equol, other treatments like Ginkgo biloba and cocoa polyphenols have shown promise in improving cognitive function in people with mild cognitive impairment. These treatments have been associated with better memory, attention, and reduced progression to dementia, suggesting that similar natural compounds might also be beneficial. ^{1 2 3 4 5}

Is Equol safe for human use?

The available research does not provide specific safety data on Equol for cognitive impairment, but studies on similar supplements suggest that while some herbal supplements can cause serious side effects, others like PM-EE have shown no significant adverse events in short-term studies. It's important to consult with a healthcare provider before starting any new supplement. ^{6 7 8 9 10}

How does the drug Equol differ from other treatments for cognitive impairment?

Equol is unique because it is a plant-derived compound known as a flavonoid, which may help improve memory and learning by interacting with brain cells and reducing inflammation. Unlike some other treatments, it is derived from natural sources and may offer a dietary approach to managing cognitive decline. ^{1 2 11 12 13}

Research Team

Akira Sekikawa, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

Healthy volunteers aged 65-85, either European or African American, who can consent and are willing to be randomly assigned to a treatment group. Excluded are those with certain medical conditions like heart failure, untreated depression, severe allergies to soy isoflavones, recent cancer treatment or stroke, extreme obesity (BMI ≥40), or any condition that makes MRI unsafe.

Inclusion Criteria

I am willing to be assigned randomly to either the treatment or placebo group.

I am between 65 and 85 years old and of European or African American descent.

Individuals who are able to provide informed consent

Exclusion Criteria

Individuals with Quick Dementia Rating System (QDRS) score ≥ 6.0

White blood cell count <3,000 or >15,000

Individuals whose score for the Telephone Interview for Cognitive Status is 22 and below

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants take Equol tablets daily for 24 months to assess effects on arterial stiffness and cognition

24 months

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Equol
• Placebo

Trial Overview The ACE Trial is testing if Equol, a dietary supplement derived from soybeans with estrogen-like effects, can slow down arterial stiffening and cognitive decline in healthy older adults. Participants will take Equol daily for two years and undergo regular clinic visits including MRI scans and memory tests.

Participant Groups

Group I: Equol Arm Experimental Treatment 1 Intervention

S-equol - 10 mg per day tablet for 24 months.

Group II: Placebo Arm Placebo Group 1 Intervention

10 mg per day for 24 months of tablets that will be of the same size/shape/color as the experimental tablet.

Who Is Running the Clinical Trial?

Akira Sekikawa

Lead Sponsor

Trials

1

Recruited

370+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

In a study of 55 patients with mild cognitive impairment (MCI), those who consumed higher amounts of cocoa polyphenols showed significantly less cognitive decline over one year compared to those who did not, suggesting a potential protective effect against worsening cognition.

Among patients who did not worsen, 46.2% experienced cognitive improvement and were treated with cocoa polyphenols, indicating that dietary supplementation may help in managing MCI and delaying progression to dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of Cocoa Polyphenols in the Treatment of Mild Cognitive Impairment: A Retrospective Study. Calabrò, RS., De Cola, MC., Gervasi, G., et al.[2023]

In a 12-month randomized controlled trial with 72 older adults, DHA fish oil supplements did not show a significant effect on cognitive measures, indicating that not all cognitively impaired older adults may benefit from DHA supplementation.

However, the study found that DHA supplementation positively impacted systolic blood pressure and reduced depression and anxiety scores in carriers of the APOE ɛ4 allele, suggesting potential benefits in mood and cardiovascular health for this specific group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of docosahexaenoic acid supplementation on cognition and well-being in mild cognitive impairment: A 12-month randomised controlled trial. Mengelberg, A., Leathem, J., Podd, J., et al.[2022]

A systematic review of 25 studies involving older adults (mean age ≥65 years) found that while some B-vitamin supplements showed cognitive benefits, the overall evidence for nutraceuticals improving cognition is not compelling, with only five studies demonstrating notable effects.

Specifically, B-vitamins were linked to improved cognitive function in certain populations, such as those with high homocysteine levels or higher baseline n-3 fatty acid status, but more research is needed to explore interactions with lifestyle and genetic factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of long-term nutraceutical and dietary supplement use on cognition in the elderly: a 10-year systematic review of randomised controlled trials. D'Cunha, NM., Georgousopoulou, EN., Dadigamuwage, L., et al.[2019]

In a 6-month randomized trial with 90 patients suffering from vascular cognitive impairment, Ginkgo biloba extract (both 120 mg and 60 mg) showed a significant positive effect on cognitive function as measured by the Clinical Global Impression score compared to placebo.

While Ginkgo biloba did not show significant improvements in other cognitive tests or ultrasound findings, it had fewer adverse reactions compared to the placebo group, suggesting it may be a safe option for patients, though further research is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Ginkgo biloba standardized extract in the treatment of vascular cognitive impairment: a randomized, double-blind, placebo-controlled clinical trial. Demarin, V., Bašić Kes, V., Trkanjec, Z., et al.[2023]

A study analyzing 110 reports of adverse reactions to herbal dietary supplements in Italy found that 23 serious reactions occurred, with 21 requiring hospitalization, highlighting significant safety concerns regarding these products.

Dermatological and cardiovascular issues were the most common reactions, and 9 out of 10 serious hepatic reactions were reported, indicating that the quality and supervision of these supplements are critical for consumer safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suspected adverse reactions to performance enhancing dietary supplements: Spontaneous reports from the Italian phytovigilance system. Ippoliti, I., Menniti-Ippolito, F., Mazzanti, G., et al.[2021]

Lifestyle interventions such as dietary changes, physical exercise, and mental activities may help reduce the risk of cognitive impairment and Alzheimer's disease in older adults, highlighting the importance of a healthy lifestyle.

Pharmacological treatments like donepezil show potential benefits for individuals with mild cognitive impairment, while other treatments like Ginkgo and certain experimental drugs have not proven effective or require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The prevention and treatment of cognitive decline and dementia: An overview of recent research on experimental treatments. Andrade, C., Radhakrishnan, R.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Mild Cognitive Impairment and Mild Dementia: The Role of Ginkgo biloba (EGb 761&#174;). [2021]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Possibilities of medical correction of moderate cognitive impairment]. [2016]

3. Spain pubmed.ncbi.nlm.nih.gov

Dietary supplements for cognitive impairment. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The Efficacy of Cocoa Polyphenols in the Treatment of Mild Cognitive Impairment: A Retrospective Study. [2023]

5. England pubmed.ncbi.nlm.nih.gov

The effects of docosahexaenoic acid supplementation on cognition and well-being in mild cognitive impairment: A 12-month randomised controlled trial. [2022]

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

Effect of long-term nutraceutical and dietary supplement use on cognition in the elderly: a 10-year systematic review of randomised controlled trials. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Ginkgo biloba standardized extract in the treatment of vascular cognitive impairment: a randomized, double-blind, placebo-controlled clinical trial. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Suspected adverse reactions to performance enhancing dietary supplements: Spontaneous reports from the Italian phytovigilance system. [2021]

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

Effect of desalted Salicornia europaea L. ethanol extract (PM-EE) on the subjects complaining memory dysfunction without dementia: a 12 week, randomized, double-blind, placebo-controlled clinical trial. [2021]

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

Evaluation of Safety and Protective Effect of Combined Extract of Cissampelos pareira and Anethum graveolens (PM52) against Age-Related Cognitive Impairment. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Effect of flavonoids on learning, memory and neurocognitive performance: relevance and potential implications for Alzheimer's disease pathophysiology. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Natural essential oils derived from herbal medicines: A promising therapy strategy for treating cognitive impairment. [2023]

13. India pubmed.ncbi.nlm.nih.gov

The prevention and treatment of cognitive decline and dementia: An overview of recent research on experimental treatments. [2021]