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

This study has been completed.
Information provided by (Responsible Party):
Robert P. Frantz, Mayo Clinic Identifier:
First received: January 7, 2010
Last updated: February 3, 2012
Last verified: February 2012
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.

Pulmonary Arterial Hypertension

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Modulating Effects of Lisinopril on Sildenafil Activity in PAH (MELISSA)

Resource links provided by NLM:

Further study details as provided by Robert P. Frantz, Mayo Clinic:

Primary Outcome Measures:
  • The primary aim of the pilot study is to assess feasibility and tolerability. [ Time Frame: 32 weeks ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 24
Study Start Date: May 2008
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Participants will be randomized 2 to 1 to receive drug versus placebo.

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

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01181284

United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Principal Investigator: Robert P Frantz, MD Mayo Clinic
  More Information

Responsible Party: Robert P. Frantz, MD, Mayo Clinic Identifier: NCT01181284     History of Changes
Other Study ID Numbers: 08-001716
Study First Received: January 7, 2010
Last Updated: February 3, 2012

Keywords provided by Robert P. Frantz, Mayo Clinic:
Pulmonary Arterial Hypertension (PAH)

Additional relevant MeSH terms:
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Sildenafil Citrate
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Antihypertensive Agents
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs processed this record on September 20, 2017