Safety and Efficacy of Fluoxetine in Pulmonary Arterial Hypertension - Full Text View

Sponsor:	University of Texas Southwestern Medical Center
Information provided by:	University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT00942708

Purpose

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

Condition	Intervention	Phase
Pulmonary Arterial Hypertension	Drug: Fluoxetine	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Safety and Efficacy of Fluoxetine in Pulmonary Arterial Hypertension

Resource links provided by NLM:

Genetics Home Reference related topics: pulmonary arterial hypertension

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Fluoxetine Fluoxetine hydrochloride

U.S. FDA Resources

Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:

The primary endpoint will be change in pulmonary vascular resistance (PVR) measured by right heart catheterization after three months of therapy. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Efficacy, Safety and tolerability endpoints will include change between baseline and three month QIDS-SR depression scale, systolic and diastolic blood pressure (systemic) and tabulation of adverse events [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	10
Study Start Date:	September 2009
Estimated Study Completion Date:	August 2011
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Fluoxetine Fluoxetine will be added starting at 20 mg and titrated as tolerated to 80 mg daily.	Drug: Fluoxetine Total dose How to take: Week 1-2 20 mg daily Week 3-4 40 mg daily Week 5-6 40 mg BID Week 7-12 40mg BID Other Names: Total dose How to take: Week 1-2 20 mg daily Week 3-4 40 mg daily Week 5-6 40 mg BID Week 7-12 40mg BID

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 three months of therapy.

Secondary endpoints

Efficacy:

Other three month catheterization variables: right atrial pressure, pulmonary arterial pressure, Fick cardiac output, pulmonary arterial oxygen saturation, pulmonary capillary wedge pressure
Six minute walk distance
WHO functional class
Brain natriuretic peptide

Safety and tolerability endpoints will include change between baseline and three 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

Eligibility

Ages Eligible for Study:	16 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Signed informed consent prior to any study-mandated procedure
PAH of the following subtypes: idiopathic PAH WHO functional class II-III
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
Age 16-75
Able to complete a six minute walk distance
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:

PAH with connective tissue disease, congenital heart disease, portal hypertension, glycogen storage disease, Gaucher's disease, hereditary hemorrhagic telangiectasia, hemoglobinopathy, myeloproliferative disorders.
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.
Systemic systolic blood pressure <100 mmHg Breastfeeding
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00942708

Contacts

Contact: Kelly M Chin, MD	214-645-6486	kelly.chin@utsouthwestern.edu
Contact: David Gallego	214-645-6489	david.gallego@utsouthwestern.edu

Locations

United States, Texas
UT Southwestern Medical Center	Recruiting
Dallas, Texas, United States, 75390
Contact: Kelly M Chin, MD 214-645-6486 kelly.chin@utsouthwestern.edu
Contact: David Gallego 214-645-6489 david.gallego@utsouthwestern.edu
Principal Investigator: Kelly M Chin, MD
Sub-Investigator: Fernando Torres, MD
Sub-Investigator: Martha S Kingman, FNP-C
Sub-Investigator: Scarlett Harden, ACNP

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Investigators

Principal Investigator:

Kelly M Chin, MD

UT Southwestern Medical Center

More Information

No publications provided

Responsible Party:	Kelly Chin, MD / Principal Investigator, UT Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT00942708 History of Changes
Other Study ID Numbers:	CTSA NIH Grant UL1-RR024982
Study First Received:	July 19, 2009
Last Updated:	March 15, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Texas Southwestern Medical Center:

Pulmonary Arterial Hypertension
Pulmonary Hypertension

Additional relevant MeSH terms:

Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Fluoxetine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012