Modulating Effects of Lisinopril on Sildenafil Activity in Pulmonary Arterial Hypertension(PAH)( MELISSA) (MELISSA)
This study has been completed.
Sponsor:
Mayo Clinic
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
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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:
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 (Adult, Senior) |
| 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
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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
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 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by 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 Sildenafil Citrate Lisinopril 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 |
ClinicalTrials.gov processed this record on September 28, 2016