LCZ 696 for Type 2 Diabetes

Overseen By Lynn Harstad

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Oral hypoglycemics, Insulin

Must not be taking: Loop diuretics

Disqualifiers: Heart failure, Myocardial infarction, Stroke, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called LCZ 696 (also known as Entresto, a combination of sacubitril and valsartan) for individuals with type 2 diabetes. Researchers aim to determine if this treatment can prevent heart problems in people with diabetes, particularly those at risk of developing heart failure. Participants will receive either the actual treatment or a placebo (a pill with no active ingredients) to compare effects. This trial suits individuals with type 2 diabetes who are on diabetes medication and can walk a fair distance without becoming breathless. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking a loop diuretic. You must also be on at least one diabetes medication for at least 6 months.

Is there any evidence suggesting that LCZ 696 is likely to be safe for humans?

Research has shown that LCZ 696, also known as sacubitril/valsartan, has been tested in various situations. In past studies, most participants tolerated sacubitril/valsartan well. Common side effects included low blood pressure, kidney issues, and high potassium levels. Angioedema, or swelling under the skin, was a specific concern but occurred rarely.

For individuals with type 2 diabetes, studies in diabetic rats indicated that sacubitril/valsartan improved heart function and other health markers more effectively than some other treatments.

Overall, while possible side effects exist, previous studies have demonstrated the treatment's safety for ongoing research. These are important considerations for those thinking about joining a trial. It is crucial to consult a doctor to understand the risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for type 2 diabetes?

Unlike the standard treatments for type 2 diabetes, which typically include medications like metformin and insulin that primarily focus on managing blood sugar levels, LCZ 696 offers a novel approach. LCZ 696 is an investigational drug that combines two components to both lower blood pressure and potentially benefit heart function, which is particularly important for diabetic patients who often face cardiovascular risks. Researchers are excited about LCZ 696 because it targets the heart and kidney protective pathways, offering potential advantages beyond traditional glucose control. This dual action could lead to improved outcomes for people with type 2 diabetes, addressing not just blood sugar but also enhancing cardiovascular health.

What evidence suggests that LCZ 696 might be an effective treatment for type 2 diabetes?

In this trial, participants will receive either LCZ 696, also known as sacubitril/valsartan, or a placebo. Research has shown that LCZ 696 might help manage diabetes by improving blood sugar control. Specifically, studies found that this treatment lowered HbA1c levels, which measure long-term blood sugar, in people with diabetes. LCZ 696 also demonstrated protective effects on blood vessels in diabetic models, suggesting it may offer more benefits than some current treatments like valsartan. Overall, these findings suggest that LCZ 696 could be effective for people with type 2 diabetes, especially those at risk for heart problems. ^{6 7 8 9 10}

Who Is on the Research Team?

Horng H Chen

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults with Type 2 diabetes who may or may not have early heart muscle dysfunction but no symptoms of heart failure. They must be on diabetes medication for at least 6 months and able to walk a certain distance. People with severe kidney issues, recent serious heart conditions, extreme blood levels (like potassium), or other health problems that could affect the study can't join.

Inclusion Criteria

I have type 2 diabetes.

I can walk more than 450 meters in 6 minutes, or less if due to hip/knee pain.

My heart pumps well and I've never had heart failure.

Exclusion Criteria

In the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any reason

Your HbA1C level is higher than 9% when you join the study.

Your blood sodium levels are very low (< 125 mEq/dL) or very high (> 160 mEq/dL).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Consent and Initial Assessment

Participants meet with study coordinator to review consent form, perform a 6-minute walk, receive diet instructions, and undergo initial lab tests and physical exam.

1 day

1 visit (in-person)

Treatment Phase 1

Participants undergo baseline assessments, receive either oral placebo or ARNI, and undergo saline infusion with repeated clearances and monitoring.

1 day

1 visit (in-person)

Washout and Crossover

Participants undergo a washout period before the crossover study.

1 week

Treatment Phase 2

Participants undergo the same procedures as Treatment Phase 1, receiving the alternate medication.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LCZ 696
• Placebos

Trial Overview The study is testing LCZ 696, a drug that might prevent worsening of heart function in diabetics compared to a placebo (a dummy pill). Participants will either receive LCZ 696 or the placebo to see if it helps manage their condition without causing further complications.

How Is the Trial Designed?

Group I: LCZ 696 Active Control 2 Interventions

1st Experimental Arm will be 1 capsule of LCZ 696 given orally, one time

Group II: Placebos Placebo Group 1 Intervention

Control Intervention will be 1 Placebo Capsule given orally, one time

LCZ 696 is already approved in United States, European Union for the following indications:

Approved in United States as Entresto for:

• Heart failure with reduced ejection fraction (NYHA Class II-IV)

Approved in European Union as Entresto for:

• Heart failure with reduced ejection fraction (NYHA Class II-IV)

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10053359/

The impact of sacubitril/valsartan on outcome in patients ... Data have shown that the HbA1c levels in patients with diabetes mellitus could be impacted by sacubitril/valsartan. A possible positive effect in diabetes ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11374559/

LCZ696, an Angiotensin Receptor-Neprilysin Inhibitor ... Our findings suggest that LCZ696 has a vascular protective effect in a diabetic model and highlight that it may be more effective than valsartan.

3. novartis.com novartis.com/us-en/news/media-releases/new-analysis-shows-novartis-entresto-improves-glycemic-control-reduced-ejection-fraction-heart-failure-patients-diabetes

New analysis shows Novartis Entresto improves glycemic ... Entresto lowered HbA1c levels – a measure of average blood glucose levels for the past two to three months – after one year of treatment for HF, and this effect ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S193317111730147X

Pharmacokinetic, pharmacodynamic, and antihypertensive ... Recent studies have shown the LCZ-696 to be very effective in patients with hypertension, including severe hypertension as well as HF.10, 15, 17, 18, 19, 20, 21 ...

5. researchgate.net researchgate.net/publication/368376183_Theuse_of_LCZ-696SacubitrilValsartan_and_SGLT2inhibitors_A_Real_World_Experience_in_a_Rural_African_Patient_with_Heart_Failure_with_Reduced_Ejection_Fraction_HFrEF_A_Case_Series

(PDF) Theuse of LCZ-696(Sacubitril/Valsartan) and ... A reduction of 52% was observed in HFrEF patients, whereas a reduction of 28.7% was observed in HFmrEF pateints. Sacubitril/valsartan reduced ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11357838/

Safety Outcomes After Sacubitril/Valsartan Initiation in a ... Primary safety outcomes will include discontinuation of sacubitril/valsartan, incidence of angioedema, hyperkalemia, AKI, hypotension, and ...

7. diabetesjournals.org diabetesjournals.org/diabetes/article/67/8/1616/16981/Vascular-and-Neural-Complications-in-Type-2

Vascular and Neural Complications in Type 2 Diabetic Rats The results demonstrated efficacy of sacubitril/valsartan in improving vascular and neural function was superior to valsartan alone. In the ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0753332222007715

Sacubitril/valsartan combination enhanced cardiac ... Results. Sacubitril/valsartan administration to diabetic rats resulted in improvement of metabolic changes more than valsartan alone. Also, sacubitril/valsartan ...

9. cdt.amegroups.org cdt.amegroups.org/article/view/19895/html

Sacubitril/valsartan: a cardiovascular drug with pluripotential ... After an 8-week follow-up, sacubitril/valsartan decreased the clinic BP by 14.2/7.5 mmHg compared to olmesartan of 10.0/4.5 mmHg and the 24-hour ABP by 4.3/2.3 ...

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36479630/

The impact of sacubitril/valsartan on outcome in patients ... Data have shown that the HbA1c levels in patients with diabetes mellitus could be impacted by sacubitril/valsartan. A possible positive effect ...