Combination Blood Pressure Therapy for High Blood Pressure

Recruiting in Palo Alto (17 mi)

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Waitlist Available

Sponsor: Vanderbilt University Medical Center

No Placebo Group

Prior Safety Data

Trial Summary

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.

Research Team

Eligibility Criteria

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.

See 3 more

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%.

See 26 more

Treatment Details

Interventions

BNP (Natriuretic Peptide)
Bradykinin (Kinins)
LCZ696 (Angiotensin Receptor Blocker/Neprilysin Inhibitor)
Sitagliptin (Dipeptidyl Peptidase 4 Inhibitor)
Substance P (Neuropeptide)
Valsartan (Angiotensin Receptor Blocker)

Trial OverviewThe 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.

Participant Groups

2Treatment groups

Active Control

Group I: valsartan then LCZ696Active Control6 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 valsartanActive Control6 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.