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

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ClinicalTrials.gov Identifier: NCT01181284
Recruitment Status : Completed
First Posted : August 13, 2010
Last Update Posted : February 7, 2012
Sponsor:
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
Change History
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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
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
Removed Location Countries  
 
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