S-equol for Chronic Kidney Disease

Overseen By Emily Andrews

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether S-equol, a compound derived from soy, can improve blood vessel function in women with chronic kidney disease (CKD), potentially reducing their risk of heart problems. Researchers focus on postmenopausal women because CKD affects their heart health and menstrual cycles differently than men. Participants will try both S-equol and a placebo in separate sessions to observe the effects. Women with CKD who do not require dialysis and do not have hypertension, diabetes, or other major diseases may be suitable candidates. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

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 there any evidence suggesting that S-equol is likely to be safe for humans?

Research has shown that S-equol might safely improve blood vessel health. It is being considered as an alternative to hormone replacement therapy, often used for similar health issues. Studies suggest that equol, a compound found in soy, can enhance blood vessel function by reducing oxidation and inflammation.

Although more information is needed about its effects on women with chronic kidney disease (CKD), it appears safe. Equol has been studied in other contexts, and these studies have not identified any major safety concerns, indicating that most people can tolerate it well. However, since this clinical trial is in an early stage, monitoring for any unexpected side effects remains crucial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic kidney disease?

Unlike the standard treatments for chronic kidney disease, which often include medications like ACE inhibitors or angiotensin II receptor blockers, S-equol is unique because it is derived from soy and acts as a selective estrogen receptor modulator (SERM). This means it can potentially provide kidney benefits by mimicking some positive effects of estrogen without the hormone's usual side effects. Researchers are excited about S-equol because it offers a novel approach that could complement existing therapies, potentially improving kidney function or slowing disease progression in a way current treatments do not.

What evidence suggests that S-equol might be an effective treatment for chronic kidney disease?

Research has shown that S-equol, which participants in this trial may receive, can improve heart and blood vessel health by reducing damage and swelling in the body. Previous studies found that equol helps with blood flow and lowers inflammation. These benefits might be particularly useful for women with chronic kidney disease (CKD), who often face a higher risk of heart issues. Although specific data for women with CKD is not yet available, these findings suggest that S-equol could be promising for improving their heart and blood vessel health. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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 2 Interventions

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+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07194590

Equol and Vascular Function in Women With Chronic ... Equol contributes to improvement in vascular function, mediated in part by its anti-oxidative and anti-inflammatory properties.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7481967/

Role of S-Equol, Indoxyl Sulfate, and Trimethylamine N-Oxide ... During uremia, however, the reduced renal clearance of indoxyl sulfate results in elevated circulating levels, as observed in patients with chronic kidney ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0009912014002823

Effect of whole soy and purified isoflavone daidzein on ... The aim of the study was to examine the long-term effect of commonly used whole soy foods (soy flour) and purified daidzein (one major isoflavone and the ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06128278

Acute Equol Supplementation and Vascular Function in ... Equol contributes to improvement in vascular function, mediated in part by its anti-oxidative and anti-inflammatory properties.

5. researchgate.net researchgate.net/publication/275049915_Effects_of_soy_protein_containing_isoflavones_in_patients_with_chronic_kidney_disease_A_systematic_review_and_meta-analysis

Effects of soy protein containing isoflavones in patients with ... Recent studies have demonstrated mixed results on the effects of soy intake in patients with CKD, and this have not been systematically ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0261561415000874

Effects of soy protein containing isoflavones in patients with ... Recent studies have demonstrated mixed results on the effects of soy intake in patients with CKD, and this have not been systematically analyzed.

7. reporter.nih.gov reporter.nih.gov/search/15EEC10D4C8DC5D37598B8961CAA4A01A2FFCEB861BF/project-details/11113106

Project Details This study has the potential to identify equol as a novel, safe, alternative compound to hormone replacement therapy for improving CKD-associated vascular ...