Modulating Effects of Lisinopril on Sildenafil Activity in Pulmonary Arterial Hypertension(PAH)( MELISSA) - Full Text View

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:

Genetics Home Reference related topics: pulmonary arterial hypertension

Drug Information available for: Lisinopril Sildenafil

Genetic and Rare Diseases Information Center resources: Pulmonary Arterial Hypertension

U.S. FDA Resources

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)

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 (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.

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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


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

Keywords provided by Robert P. Frantz, Mayo Clinic:


Pulmonary Arterial Hypertension (PAH)

Additional relevant MeSH terms:


Hypertension Familial Primary Pulmonary Hypertension Vascular Diseases Cardiovascular Diseases Hypertension, Pulmonary Lung Diseases Respiratory Tract Diseases Lisinopril Sildenafil Citrate Angiotensin-Converting Enzyme Inhibitors Protease Inhibitors	Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antihypertensive Agents Cardiotonic Agents Protective Agents Physiological Effects of Drugs Vasodilator Agents Phosphodiesterase 5 Inhibitors Phosphodiesterase Inhibitors Urological Agents

ClinicalTrials.gov processed this record on June 23, 2017

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