Equol for Cognitive Impairment

(ACE Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the dietary supplement Equol can slow memory decline and address issues with small blood vessels in the brain. Equol, a compound found in soy, may help due to its plant estrogen-like properties. Participants will receive either Equol or a placebo for two years to determine any differences. The trial seeks participants aged 65 to 85 who have noticed memory changes and do not regularly consume soy products. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Equol, a supplement made from soy, is under study for its potential to slow memory loss and improve heart health. Previous studies have found that people generally tolerate Equol well, with no major reports of serious side effects.

In Japan, research has found that people who naturally produce Equol tend to have better thinking and memory skills as they age. This suggests that Equol might be safe and beneficial for brain health. Although specific data from U.S. studies is not yet available, the FDA has approved its use in this trial, indicating its safety in humans.

Overall, existing research supports the idea that Equol is safe to use, with little risk of harmful effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for cognitive impairment, which often involve medications like cholinesterase inhibitors and memantine, Equol uses a novel approach. Equol is a compound derived from soy that mimics estrogen, which might help protect brain cells and improve cognition. Researchers are excited because Equol offers a potentially safer alternative with fewer side effects than current medications, and it targets the underlying biological processes differently by utilizing its unique interaction with estrogen receptors. This could open up new avenues for treating cognitive impairment, especially for those who cannot tolerate existing medications.

What evidence suggests that Equol might be an effective treatment for cognitive impairment?

Research has shown that Equol, a supplement derived from soy, might help slow memory loss. Studies indicate that individuals who naturally produce Equol exhibit better brain function than those who do not, suggesting that Equol might protect the brain. This trial will compare Equol with a placebo to evaluate its effectiveness. Equol appears to interact with specific brain regions that respond to estrogen, potentially promoting brain health. However, no studies in the U.S. have yet confirmed these effects. ^{1 2 3 6 7}

Who Is on the Research Team?

Akira Sekikawa, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

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.

Individuals who are able to provide informed consent

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05741060

Effect of Equol Supplementation on Arterial Stiffness and ... The subgroup analysis of WISH showed that equol producers had better cognition than the control group, suggesting that equol may slow cognitive decline. No ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6520578/

Effect of S-equol and Soy Isoflavones on Heart and Brain Therefore, potentially, soy isoflavones, especially S-equol, are protective against cognitive decline/dementia. Methods/Results: This narrative review of ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12361350/

ACE trial design: Equol targeting estrogen receptor‐β in ... Cognitive decline (PACC5) will be analyzed similarly, using data from baseline, 12, and 24 months, adjusting for baseline cognitive status, and ...

4. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/S-equol.pdf

S-equol However, in observational studies, S-equol producers appear to be protected from cognitive decline. Aging and related health concerns: S-equol ...

5. mdpi.com mdpi.com/1422-0067/23/19/11921

Potential Protective Mechanisms of S-equol, a Metabolite ... These results suggest that S-equol rather than soy isoflavones slows cognitive decline. ... Cross-sectional study of equol producer status and cognitive ...

6. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.12089

Associations of equol‐producing status with white matter ... A recent cross-sectional study in elderly Japanese reported that equol producers had significantly higher cognitive scores and lower prevalence ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28345266/

Cross-sectional study of equol producer status and ... Compared with equol non-producers, equol producers showed an apparent beneficial effect in cognitive function after soy intake.