Modulating Effects of Lisinopril on Sildenafil Activity in Pulmonary Arterial Hypertension(PAH)( MELISSA)

Completed

• Conditions: Pulmonary Arterial Hypertension

• Registration Number: NCT01181284
• Lead Sponsor: Mayo Clinic

Brief Summary

Patients with pulmonary arterial hypertension(PAH) suffer from chronic shortness of breath, and have impaired survival related to progressive right ventricular failure. Abnormal vasoreactivity to nitric oxide(NO) plays a role in the pathophysiology of PAH. Phosphodiesterase Type 5 Inhibitor (PDE5 inhibitors) sildenafil have been shown to be beneficial in PAH, but extent of benefit is variable.

Detailed Description

The broad aim of this investigation is to determine whether the modulating effect of angiotensin converting enzyme inhibition on vascular smooth muscle responsiveness to the nitric oxide pathway that we have observed in an animal model of Congestive Heart Failure(CHF) can be exploited in humans with PAH. Furthermore, we have identified a group of genes TAO kinase I, IL-10, Rho kinase, Raf1, bile acid coenzyme A and Fmr1 that are modulated by long-acting angiotensin-converting enzyme inhibitor (ACEI) in our animal model, and therefore may also be modulated by ACEI in patients with PAH

Study Timeline

• Study Start: 2008-05
• Study First Submitted: 2010-01-07
• Study First Submitted QC: 2010-08-12
• Study First Posted: 2010-08-13
• Primary Completion: 2011-07
• Study Completion: 2011-07
• Status Verified: 2012-02
• Last Update Submitted: 2012-02-03
• Last Update Posted: 2012-02-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Age 18-75
• World Health Organization (WHO) Group I PAH with prior documentation of peripheral vascular resistance (PVR) > 3 WU and wedge(PCW) 16 or less.
• WHO Functional Class I-III
• 6 minute walk distance 150-575 meters
• Women of child bearing potential must have a negative pregnancy test and be using effective contraception
• Receiving therapy with phosphodiesterase-5 inhibitor for PAH (sildenafil or tadalafil) for at least 3 months and with stable dose for at least 30 days
• If already receiving therapy with endothelin receptor antagonists must have been on therapy for at least 3 months and on stable dose for at least 30 days

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Exclusion Criteria

• Allergy or intolerance to captopril or other angiotensin converting enzyme inhibitors
• Systemic systolic blood pressure less than 100 mm Hg
• Therapy with prostanoids (iloprost, treprostinil, epoprostenol) within preceding 3 months
• Pregnant or breast feeding
• Creatinine > 2.0 mg/dl
• Potassium > 5.0 meq/dl
• Unable to provide informed consent
• TLC or VC <60% predicted
• Untreated obstructive sleep apnea
• LVEF < 40%
• Hb < 10 mg/dL

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary aim of the pilot study is to assess feasibility and tolerability.	32 weeks

Secondary Outcome Measures

Name	Time	Method
Demonstrate tolerability of long-acting angiotensin-converting enzyme inhibitor (ACEI) therapy in this patient cohort	32 weeks
Demonstrate whether long-acting angiotensin-converting enzyme inhibitor (ACEI) in Pulmonary Arterial Hypertension (PAH) pts on sildenafil modifies regulation of the genes.	32 weeks
Demonstrate whether ACEI in PAH pts on sildenafil reduces N-BNP levels, a marker of disease severity	32 weeks
Demonstrate whether ACEI in PAH pts on sildenafil has an effect on pulmonary gas exchange parameters (exhaled NO, Dm, Vc, DLCO).	32 weeks
Obtain exploratory data regarding whether ACEI in PAH pts on sildenafil improves functional class and 6 minute walk distance.	32 weeks

Trial Locations

Locations (1)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States