Empagliflozin for Arterial Stiffness

(ERASE-Aging Trial)

Overseen By Andrea Atkins, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of Missouri-Columbia

Must not be taking: Hormone replacement, Nitrate medications

Disqualifiers: Diabetes, Cardiovascular disease, Cancer, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called empagliflozin to determine if it can reduce arterial stiffening, a condition where arteries become less flexible with age. The trial compares empagliflozin to a placebo (a non-active pill) to assess its effectiveness over 12 weeks. It seeks participants aged 60 to 80 who show signs of arterial stiffening and maintain a stable blood pressure medication routine. This trial might be a good fit for those who meet these criteria. As a Phase 2, Phase 3 trial, the research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering a chance to contribute to significant advancements in treatment.

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 must have a stable anti-hypertensive medication regimen for at least 90 days if you are using such medications.

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

Research has shown that empagliflozin is generally safe for people. Studies have found that it can improve blood vessel health and lower blood pressure, suggesting good tolerance. In individuals with type 1 diabetes, empagliflozin has been linked to better blood vessel health without major side effects.

Although these studies did not specifically focus on older adults, they suggest that the treatment may be safe. The FDA has approved empagliflozin for other conditions, indicating it has passed safety checks for those uses. Based on this, the treatment appears well-tolerated, but consulting a doctor before joining any trial is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Empagliflozin is unique because it targets arterial stiffness by acting as a sodium-glucose cotransporter-2 (SGLT2) inhibitor, a mechanism not commonly used for this condition. While most treatments for arterial stiffness focus on lowering blood pressure or cholesterol, empagliflozin works by reducing the amount of sugar reabsorbed in the kidneys, which can also lead to improved vascular function. Researchers are excited about empagliflozin because it offers a novel approach that could improve heart health in patients who might not respond well to traditional therapies.

What evidence suggests that empagliflozin might be an effective treatment for arterial stiffness?

Research shows that empagliflozin, which participants in this trial may receive, can make blood vessels more flexible and less stiff. One study found that it improved blood vessel flexibility and reduced resistance, aiding blood flow. Another study showed that after 12 weeks of treatment, empagliflozin significantly enhanced blood vessel flexibility in people with type 2 diabetes. Additionally, a study comparing empagliflozin to a placebo confirmed these benefits, suggesting it might help various groups. These findings suggest that empagliflozin could reduce the stiffening of blood vessels associated with aging. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for men and women aged 60-80 who experience arterial stiffness as they age. Participants must be able to consent, have a specific measure of arterial stiffness (carotid femoral PWV >9.5 m/s), and if taking blood pressure medication, it should be stable for at least 90 days.

Inclusion Criteria

My heart to leg artery pulse speed is over 9.5 m/s.

I am capable of understanding and agreeing to the study's procedures.

My blood pressure medication has not changed in the last 90 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 10mg of Empagliflozin or placebo daily for 12 weeks

12 weeks

Visits at baseline, week 4, week 8, and week 12

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Empagliflozin

Trial Overview The study tests whether Empagliflozin (10mg daily) can reduce arterial stiffening associated with aging compared to a placebo. It's a randomized controlled trial involving 80 participants over the course of 12 weeks.

How Is the Trial Designed?

Group I: Empagliflozin Experimental Treatment 1 Intervention

10mg Empagliflozin daily for 12 weeks

Group II: Placebo Placebo Group 1 Intervention

10mg Placebo daily for 12 weeks

Empagliflozin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in United States as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease
• Cardiovascular risk reduction

Approved in Canada as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction
• Chronic kidney disease

Approved in Japan as Jardiance for:

• Type 2 diabetes mellitus
• Heart failure with reduced ejection fraction

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Published Research Related to This Trial

Empagliflozin (Jardiance) is now approved for reducing the risk of cardiovascular death and hospitalization in adults with heart failure, even in those without diabetes, highlighting its expanded therapeutic use.

Healthcare providers, including nurses and nurse practitioners, should closely monitor patients for potential adverse effects, particularly fluid deficits, to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes Drug Now Approved for Heart Failure. Aschenbrenner, DS.[2023]

In a study of 58 patients with type 2 diabetes, empagliflozin significantly improved arterial stiffness, as shown by reductions in central systolic blood pressure and pulse pressure after 6 weeks of treatment compared to placebo.

The improvement in arterial stiffness was linked to changes in inflammatory markers (hsCRP) and blood pressure, suggesting that empagliflozin may exert its vascular benefits through anti-inflammatory mechanisms rather than changes in glucose metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How does empagliflozin improve arterial stiffness in patients with type 2 diabetes mellitus? Sub analysis of a clinical trial. Bosch, A., Ott, C., Jung, S., et al.[2020]

Empagliflozin effectively lowers blood sugar levels in patients with type 2 diabetes by inhibiting glucose reabsorption in the kidneys, resulting in an average reduction of HbA1c by approximately 0.8% without causing hypoglycemia, except in those already on insulin or sulphonylureas.

In addition to improving glycemic control, empagliflozin promotes weight loss (about 2 kg) and lowers blood pressure (systolic by approximately 4 mm Hg), while also providing cardiovascular protection, as demonstrated in the EMPA-REG OUTCOME trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EMPAGLIFLOZIN (JARDIANCE) :Nw SGLT2 COTRANSPORTER INHIBITOR FOR TREATING TYPE 2 DIABETES]. Scheen, AJ.[2022]

In the EMPEROR-Reduced study involving over 3700 participants with chronic heart failure and reduced ejection fraction, empagliflozin significantly reduced the risk of hospitalization for heart failure complications (13.2% vs. 18.3% for placebo) over an average of 16 months.

Empagliflozin also showed a lower incidence of serious kidney problems (1.6% vs. 3.1% for placebo), indicating its potential safety and efficacy in managing heart failure, although it was associated with a higher rate of genital tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. Zannad, F., Macari, S.[2023]

A study involving 60 healthy Chinese subjects demonstrated that the test formulation of empagliflozin is bioequivalent to the brand-name drug Jardiance, showing similar pharmacokinetic properties under both fasting and fed conditions.

Both formulations of empagliflozin were generally well tolerated, indicating a good safety profile for the drug in the tested populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Safety, and Bioequivalence of Two Empagliflozin Formulations after Single Oral Administration under Fasting and Fed Conditions in Healthy Chinese Subjects: An Open-label Randomized Single-dose Two-sequence, Two-treatment, Two-period Crossover Study. Chen, G., Zhang, D., Du, A., et al.[2021]

In the EMPA-REG OUTCOME trial involving 7020 patients with type 2 diabetes and atherosclerotic cardiovascular disease, empagliflozin significantly reduced the risk of major adverse cardiovascular events by 22% compared to placebo, indicating its efficacy in lowering cardiovascular complications.

Empagliflozin also led to a 42% reduction in hospital admissions for heart failure and an 17% reduction in all-cause hospital admissions, demonstrating its potential to improve overall patient outcomes in this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of empagliflozin on first and recurrent clinical events in patients with type 2 diabetes and atherosclerotic cardiovascular disease: a secondary analysis of the EMPA-REG OUTCOME trial. McGuire, DK., Zinman, B., Inzucchi, SE., et al.[2022]

Empagliflozin (Jardiance®) is an effective treatment for type 2 diabetes (T2D) that works by inhibiting the sodium glucose cotransporter-2 (SGLT2), and it also offers cardioprotective and renoprotective benefits, making it particularly suitable for patients with cardiovascular disease (CVD) and chronic kidney disease (CKD).

While empagliflozin is generally well-tolerated and easy to administer, it does have some side effects and contraindications that need to be considered, highlighting the importance of evaluating its benefits against potential risks in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dual role of empagliflozin: Cardio renal protection in T2DM patients. Shafiq, A., Mahboob, E., Samad, MA., et al.[2022]

Empagliflozin (Jardiance) has been associated with a significant reduction in cardiovascular mortality among patients with type 2 diabetes and established cardiovascular disease, although the exact mechanism for this benefit is not yet understood.

There is uncertainty regarding whether empagliflozin may also increase the risk of fractures, a concern raised with another SGLT2 inhibitor, canagliflozin (Invokana), and all SGLT2 inhibitors are noted to have only modest effectiveness in managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGLT2 inhibitors: new reports. [2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40430228/

Empagliflozin Leads to Faster Improvement in Arterial ... Dapagliflozin has shown rapid effects on arterial stiffness, but there is limited evidence of empagliflozin's acute effects, especially in type ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1504720

Empagliflozin, Cardiovascular Outcomes, and Mortality in ... Empagliflozin also has favorable effects on markers of arterial stiffness and vascular resistance, visceral adiposity, albuminuria, and plasma ...

3. academic.oup.com academic.oup.com/eurheartj/article/45/Supplement_1/ehae666.3301/7839087

Empaglifozin modifies the arterial stiffness in type-2 diabetic ... Empagliflozin treatment significantly decreased HbA1c after 12 weeks of treatment (7.9±0.78 vs 7.04±1.09%, P < 0.008.). After 12 weeks' ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24475922/

The effect of empagliflozin on arterial stiffness and heart ... Conclusions: Empagliflozin is associated with a decline in arterial stiffness in young type 1 diabetes mellitus subjects. The underlying ...

5. cardiab.biomedcentral.com cardiab.biomedcentral.com/articles/10.1186/s12933-019-0839-8

How does empagliflozin improve arterial stiffness in patients ... Most recently we have shown that empagliflozin improves arterial stiffness in a double blind, placebo controlled, crossover clinical trial ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5057299/

Effects of empagliflozin on blood pressure and markers of ... Empagliflozin reduced BP and had favourable effects on markers of arterial stiffness and vascular resistance. Keywords: cardiovascular disease, phase III study, ...

7. cardiab.biomedcentral.com cardiab.biomedcentral.com/articles/10.1186/1475-2840-13-28

The effect of empagliflozin on arterial stiffness and heart rate ... Empagliflozin is associated with a decline in arterial stiffness in young type 1 diabetes mellitus subjects.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03639545

The Effects of Empagliflozin on Arterial Wall Characteristics In patients with type 1 diabetes, favorable effects of empagliflozin on the reduction of arterial wall stiffness and blood pressure reduction ...

9. ahajournals.org ahajournals.org/doi/10.1161/circulationaha.117.028268

Empagliflozin and Clinical Outcomes in Patients With Type ... This is supported by evidence that empagliflozin reduces arterial stiffness and cardiac workload, which may be a consequence of reduced blood ...