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

• ClinicalTrials.gov Identifier: NCT01181284
• Recruitment Status: Completed
• First Posted: August 13, 2010
• Last Update Posted: February 7, 2012
• Sponsor: Mayo Clinic
• Information provided by (Responsible Party): Robert P. Frantz, Mayo Clinic

Tracking Information

• First Submitted Date: January 7, 2010
• First Posted Date: August 13, 2010
• Last Update Posted Date: February 7, 2012
• Study Start Date: May 2008
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 12, 2010): The primary aim of the pilot study is to assess feasibility and tolerability. [ Time Frame: 32 weeks ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 12, 2010)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Modulating Effects of Lisinopril on Sildenafil Activity in Pulmonary Arterial Hypertension(PAH)( MELISSA)
• Official Title: Modulating Effects of Lisinopril on Sildenafil Activity in PAH (MELISSA)
• 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 Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• 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.
• Condition: Pulmonary Arterial Hypertension
• Intervention: Not Provided

Study Groups/Cohorts

Lisinopril

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 12, 2010): 24
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: July 2011
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01181284
• Other Study ID Numbers: 08-001716; MELISSA
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Robert P. Frantz, Mayo Clinic
• Study Sponsor: Mayo Clinic
• Collaborators: Not Provided

Investigators

• Principal Investigator: Robert P Frantz, MD; Mayo Clinic

• PRS Account: Mayo Clinic
• Verification Date: February 2012