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

Pulmonary Arterial Hypertension Clinical Trial

— MELISSA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01181284
• Other study ID #: 08-001716
• Secondary ID: MELISSA
• Status: Completed
• Phase: N/A
• First received: January 7, 2010
• Last updated: February 3, 2012
• Start date: May 2008
• Est. completion date: July 2011

Study information

• Verified date: February 2012
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Hypertension
• Pulmonary Arterial Hypertension

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary aim of the pilot study is to assess feasibility and tolerability.		32 weeks	No
Secondary	Demonstrate tolerability of long-acting angiotensin-converting enzyme inhibitor (ACEI) therapy in this patient cohort		32 weeks	No
Secondary	Demonstrate whether long-acting angiotensin-converting enzyme inhibitor (ACEI) in Pulmonary Arterial Hypertension (PAH) pts on sildenafil modifies regulation of the genes.		32 weeks	No
Secondary	Demonstrate whether ACEI in PAH pts on sildenafil reduces N-BNP levels, a marker of disease severity		32 weeks	No
Secondary	Demonstrate whether ACEI in PAH pts on sildenafil has an effect on pulmonary gas exchange parameters (exhaled NO, Dm, Vc, DLCO).		32 weeks	No
Secondary	Obtain exploratory data regarding whether ACEI in PAH pts on sildenafil improves functional class and 6 minute walk distance.		32 weeks	No