S-equol for Chronic Kidney Disease

Overseen By Taylor Struemph

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Immunosuppressants, Antioxidants, Omega-3s

Disqualifiers: Dialysis, Kidney transplant, Hypertension, others

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

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

Compensation: Varies

Number of Visits: 3

Duration: 1 day per treatment arm

38 Participants Needed

Trial Summary

What is the purpose of this trial?

The risk of cardiovascular disease (CVD) is significantly elevated in patients with chronic kidney disease (CKD). Notably, women with CKD commonly experience menstrual disturbances induced by CKD, which may contribute to impaired vascular function and elevated CVD risk. However, most of the literature in nephrology focuses on male patients, and studies on women's vascular health are limited. Establishing effective therapies for improving vascular function and reducing CVD risk in women with CKD is a high research priority of the NIH. Equol contributes to improvement in vascular function, mediated in part by its anti-oxidative and anti-inflammatory properties. However, there is no information on the effect of equol on vascular function in women with CKD. The proposed project aims to determine the acute effect (1-hour, 2-hours, and 3-hours post ingestion) of oral equol supplementation on vascular function in postmenopausal women with and without CKD.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use hormone replacement therapy, immunosuppressants (unless stable), antioxidants, omega-3s, or consume soy products close to the testing dates.

Is S-equol safe for humans?

Research shows that S-equol is generally safe in animals, with no significant harmful effects on reproductive development or genotoxicity (DNA damage potential). It was well-tolerated in studies, with no major changes in uterine weight or structure, and it has suitable properties for drug development. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for postmenopausal women aged 50-69, with or without chronic kidney disease (CKD). Healthy participants need no history of hypertension, CVD, diabetes, or other chronic diseases. Women with CKD must be in stages 3-4 but not on dialysis or have had a kidney transplant. Exclusions include recent hospitalization, certain heart conditions, hormone replacement therapy use within six months, and recent consumption of soy products.

Inclusion Criteria

I am a woman with moderate to severe kidney disease.

I am a woman without chronic kidney disease and no major health issues like hypertension, heart disease, or diabetes.

I am a woman aged 50-69 and have gone through menopause.

Exclusion Criteria

My blood pressure is over 140/90 mmHg and I have chronic kidney disease.

I am on a stable dose of immunosuppressants for a non-active disease.

I have been hospitalized within the last month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acute equol supplementation and placebo in a crossover design to assess vascular function

1 day per treatment arm

2 visits (in-person)

Follow-up

Participants are monitored for changes in vascular function and circulating markers post-treatment

1 day

1 visit (in-person)

Treatment Details

Interventions

• S-equol

Trial Overview The study investigates the immediate effects of S-equol supplement on vascular function in women after one hour of ingestion. It aims to see if this compound can improve blood vessel health due to its anti-inflammatory and antioxidant properties especially in those with CKD where cardiovascular risk is higher.

Participant Groups

Group I: (1) S-equol, (2) Placebo Experimental Treatment 1 Intervention

This is a randomized, placebo-controlled, crossover study. Participants in one arm will receive S-equol (one visit) and then placebo (the other visit).

Group II: (1) Placebo, (2) S-equol Experimental Treatment 1 Intervention

This is a randomized, placebo-controlled, crossover study. Participants in one arm will receive placebo (one visit) and then S-equl (the other visit).

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Findings from Research

In a study on Sprague-Dawley rats, neither S-(-)equol nor R-(+)equol affected fertility or reproductive outcomes, indicating that these soy isoflavone metabolites are safe in terms of reproductive development.

Both enantiomers caused hyperplasia (an increase in the number of cells) in uterine tissue, but while the effect of R-(+)equol was temporary, S-(-)equol led to prolonged changes, suggesting different biological actions between the two forms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of perinatal exposure to equol enantiomers on reproductive development in rodents. Brown, NM., Lindley, SL., Witte, DP., et al.[2021]

S-equol, derived from soy isoflavone daidzein, is rapidly absorbed in both rats and monkeys, showing pharmacokinetic properties that support its development for treating vasomotor symptoms in postmenopausal women.

The studies indicate that S-equol has a low potential for uterotropic effects, as it did not significantly alter uterine weight or morphology in animal models, suggesting it may be a safe option for women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicokinetics and lack of uterotropic effect of orally administered S-equol. Schwen, RJ., Nguyen, L., Plomley, JB., et al.[2014]

In a study of 1,345 postmenopausal women, those who produced equol (28.1% of participants) had a significantly lower prevalence of metabolic syndrome (METS) compared to non-producers (6.6% vs 10.9%).

The analysis indicated that equol production is associated with a reduced risk of METS, with an odds ratio of 0.60, suggesting that equol may play a protective role against metabolic disorders in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between equol production and metabolic syndrome in Japanese women in their 50s-60s. Takahashi, A., Kokubun, M., Anzai, Y., et al.[2022]

Three genotoxicity studies on S-equol, a compound derived from soy isoflavones, showed no evidence of genotoxic activity or cytotoxicity, even at high concentrations, indicating its safety for further development.

The studies adhered to Good Laboratory Practices and included various tests, confirming that S-equol does not exhibit genotoxic effects, which supports its potential as a safe therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotoxicity assessment of S-equol in bacterial mutation, chromosomal aberration, and rodent bone marrow micronucleus tests. Schwen, R., Jackson, R., Proudlock, R.[2012]

Equol significantly inhibits apoptosis in human umbilical vein endothelial cells (HUVECs) when exposed to oxidized low-density lipoprotein (OX-LDL), suggesting a protective effect against cell death.

The mechanism of action involves equol reducing superoxide production and increasing nitric oxide levels, which may lower the harmful effects of reactive oxygen species (ROS) associated with OX-LDL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of equol on oxidized low-density lipoprotein-induced apoptosis in endothelial cells. Kamiyama, M., Kishimoto, Y., Tani, M., et al.[2019]

References

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

Impact of perinatal exposure to equol enantiomers on reproductive development in rodents. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Toxicokinetics and lack of uterotropic effect of orally administered S-equol. [2014]

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

Association between equol production and metabolic syndrome in Japanese women in their 50s-60s. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Genotoxicity assessment of S-equol in bacterial mutation, chromosomal aberration, and rodent bone marrow micronucleus tests. [2012]

5. Japan pubmed.ncbi.nlm.nih.gov

Effects of equol on oxidized low-density lipoprotein-induced apoptosis in endothelial cells. [2019]