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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Robert P. Frantz, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01181284
First received: January 7, 2010
Last updated: February 3, 2012
Last verified: February 2012
History of Changes
  Purpose

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.


Condition
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:

U.S. FDA Resources

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • The primary aim of the pilot study is to assess feasibility and tolerability. [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Demonstrate tolerability of long-acting angiotensin-converting enzyme inhibitor (ACEI) therapy in this patient cohort [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Demonstrate whether ACEI in PAH pts on sildenafil reduces N-BNP levels, a marker of disease severity [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Obtain exploratory data regarding whether ACEI in PAH pts on sildenafil improves functional class and 6 minute walk distance. [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]

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)
Groups/Cohorts
Lisinopril
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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.

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

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

No publications provided

Responsible Party: Robert P. Frantz, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01181284     History of Changes
Other Study ID Numbers: 08-001716, MELISSA
Study First Received: January 7, 2010
Last Updated: February 3, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
Pulmonary Arterial Hypertension (PAH)

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Lisinopril
Sildenafil
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
 Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors

ClinicalTrials.gov processed this record on June 18, 2013