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

NCT01181284 | Completed

• 2 other identifiers: 08-001716MELISSA
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary Arterial Hypertension (PAH)

Outcome Measures

Primary Outcomes (1)

• The primary aim of the pilot study is to assess feasibility and tolerability.

  32 weeks

Secondary Outcomes (5)

• 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

Study Arms (1)

Lisinopril

Participants will be randomized 2 to 1 to receive drug versus placebo.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants will be currently diagnosed with Pulmonary Arterial Hypertension (PAH). Lisinopril versus placebo will be added to participants already recieving a stable dose of Sildenafil.

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Robert P Frantz, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 7, 2010
• First Posted: August 13, 2010
• Study Start: May 1, 2008
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: February 7, 2012

Record last verified: 2012-02

Locations

US (1)