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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

January 7, 2010
February 3, 2012
May 2008
July 2011   (final data collection date for primary outcome measure)
The primary aim of the pilot study is to assess feasibility and tolerability. [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01181284 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Modulating Effects of Lisinopril on Sildenafil Activity in Pulmonary Arterial Hypertension(PAH)( MELISSA)
Modulating Effects of Lisinopril on Sildenafil Activity in PAH (MELISSA)

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.

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

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Not Provided
Probability Sample

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.

Pulmonary Arterial Hypertension
Not Provided
Lisinopril
Participants will be randomized 2 to 1 to receive drug versus placebo.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
24
July 2011
July 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01181284
08-001716, MELISSA
No
Robert P. Frantz, Mayo Clinic
Mayo Clinic
Not Provided
Principal Investigator: Robert P Frantz, MD Mayo Clinic
Mayo Clinic
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP