Safety and Efficacy of Reserpine Alone and in Combination With Fluoxetine in Pulmonary Arterial Hypertension

Condition(s) targeted: Pulmonary Arterial Hypertension

Intervention: Reserpine and fluoxetine (Drug)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: University of Texas Southwestern Medical Center

Official(s) and/or principal investigator(s):
Kelly M Chin, MD, Principal Investigator, Affiliation: UT Southwestern Medical Center

Overall contact:
Kelly M Chin, MD, Phone: 214-645-6486, Email: kelly.chin@utsouthwestern.edu

This study will evaluate the safety, tolerability and efficacy of open-label reserpine for three months followed by reserpine plus fluoxetine for three months among patients with pulmonary arterial hypertension.

Official title: Safety and Efficacy of Reserpine Alone and in Combination With Fluoxetine in Pulmonary Arterial Hypertension

Study design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study

Primary outcome: The primary endpoint will be change in pulmonary vascular resistance (PVR) measured by right heart catheterization after six months of therapy.

Secondary outcome: Efficacy, Safety and tolerability endpoints will include change between baseline, three month and six month QIDS-SR depression scale, systolic and diastolic blood pressure (systemic) and tabulation of adverse events

Detailed description: Idiopathic pulmonary arterial hypertension (PAH) is a life-threatening disorder of uncertain cause that leads to progressive right heart failure and death. Average survival has improved from about 2. 8 years in the early 1990s to approximately 5-7 years with current treatments, but most patients will still die of their disease. Two classes of oral medications are approved for use in PAH: endothelin-1 antagonists, and phosphodiesterase-5 inhibitors. Both improve walk distance and symptoms in PAH, but most patients still have continued dyspnea, fatigue and significant elevations in pulmonary pressures. Those who remain severely impaired are generally started on a continuous intravenous prostacyclin. For those who are less ill but still symptomatic, few options are available.

Primary endpoint: the primary endpoint will be change in pulmonary vascular resistance (PVR) measured by right heart catheterization after six months of therapy.

Secondary endpoints

Efficacy:

- Other 6 month catheterization variables: right atrial pressure, pulmonary arterial

pressure, Fick cardiac output, pulmonary arterial oxygen saturation, pulmonary capillary wedge pressure

- 3 month catheterization variables

- Six minute walk distance

- WHO functional class

- Brain natriuretic peptide

Safety and tolerability endpoints will include change between baseline, three month and six month QIDS-SR depression scale, systolic and diastolic blood pressure (systemic) and tabulation of adverse events to include but not limited to:

- Death

- Hospitalization

- Symptomatic hypotension

- Gastrointestinal side effects

- Depression

Minimum age: 16 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Signed informed consent prior to any study-mandated procedure

2. PAH of the following subtypes: idiopathic PAH WHO functional class II-III

3. Catheterization within one week showing mPAP >=25, wedge or LV end diastolic pressure ≤15, and PVR > 4 wood units, and baseline fick cardiac output results available

4. Age 16-75

5. Able to complete a six minute walk distance

6. Women of childbearing potential*: negative serum pre-treatment pregnancy test + consistently and correctly uses a reliable method of contraception** Oral approved PAH therapy for >3 months with no change in dose for > 1 month

Exclusion Criteria:

1. PAH with connective tissue disease, congenital heart disease, portal hypertension, glycogen storage disease, Gaucher's disease, hereditary hemorrhagic telangiectasia, hemoglobinopathy, myeloproliferative disorders.

2. Moderate to severe obstructive or restrictive lung disease: forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 70% and FEV1 < 60% of predicted value

after bronchodilator administration. - or- total lung capacity (TLC) < 60% of

predicted.

3. Systemic systolic blood pressure <100 mmHg Breastfeeding

4. Significant liver, renal or other medical disease preventing completion of the study procedures or with life expectancy <12 months, or any other acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements

Kelly M Chin, MD, Phone: 214-645-6486, Email: kelly.chin@utsouthwestern.edu

UT Southwestern Medical Center, Dallas, Texas 75390, United States

Starting date: September 2009
Ending date: September 2010
Last updated: July 20, 2009