Combination Blood Pressure Therapy for High Blood Pressure

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Vanderbilt University Medical Center

Must be taking: Antihypertensives

Must not be taking: ACE inhibitors, NEPi, Lithium

Disqualifiers: Secondary hypertension, Cardiovascular disease, Diabetes, 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: Unknown

4 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to test the hypothesis that combined angiotensin receptor blockade (ARB)/neprilysin (NEP) inhibition potentiates the effects of exogenous bradykinin, substance P, and brain natriuretic peptide (BNP) on forearm blood flow or endothelial tissue-type plasminogen activator (t-PA) release compared to ARB alone. A secondary goal is to determine if there is an interactive effect of ARB/NEP inhibition and dipeptidyl peptidase 4 (DPP4) inhibition on responses to these peptides.

Are You a Good Fit for This Trial?

This trial is for adults with high blood pressure who've been on medication for at least six months or have certain levels of untreated blood pressure. Women must be postmenopausal, surgically sterilized, or using birth control. People can't join if they have a history of severe allergies to related drugs, low blood pressure, significant lung disorders, type 1 diabetes, very poor kidney function, recent steroid therapy or drug trials participation.

Inclusion Criteria

For female subjects, status post-surgical sterilization

I have high blood pressure that hasn't been treated, measured over 130 mmHg three times.

I have been postmenopausal for at least one year.

Exclusion Criteria

I have a serious lung condition.

I haven't had a serious brain condition like a stroke or seizure in the last 6 months.

My type 2 diabetes is not well-managed, with a HgbA1c over 9%.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3-4 weeks

Multiple visits for blood pressure monitoring

Treatment Phase 1

Participants receive valsartan or LCZ696 for four weeks, followed by intra-arterial infusions of bradykinin, substance P, and BNP

4 weeks

In-person visits for drug administration and monitoring

Washout

Participants undergo a three-week washout period before switching treatments

3 weeks

Treatment Phase 2

Participants receive the alternate drug (LCZ696 or valsartan) for four weeks, followed by intra-arterial infusions of bradykinin, substance P, and BNP

4 weeks

In-person visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BNP
• Bradykinin
• LCZ696
• Sitagliptin
• Substance P
• Valsartan

Trial Overview The study tests whether combining an angiotensin receptor blocker (Valsartan) and neprilysin inhibitor (LCZ696) affects forearm blood flow and tissue response better than the blocker alone. It also looks at how adding a DPP4 inhibitor (Sitagliptin) changes these effects when exposed to bradykinin, substance P, and BNP.

How Is the Trial Designed?

Group I: valsartan then LCZ696 Active Control 6 Interventions

After four-week treatment with valsartan, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin. Then, after three-week washout and four week therapy with LCZ696, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin.

Group II: LCZ696 then valsartan Active Control 6 Interventions

After four-week treatment with LCZ696, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin. Then, after three-week washout and four week therapy with valsartan, participants will receive intra-arterial infusions of bradykinin, substance P, and BNP in the presence and absence of sitagliptin.

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+