Safety and Efficacy of Fluoxetine in Pulmonary Arterial Hypertension

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

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Fluoxetine

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

• Six minute walk distance
• QIDS-SR depression scale

Safety and tolerability endpoints will include a tabulation of adverse events to include but not limited to:

• Death
• Hospitalization
• Symptomatic hypotension
• Gastrointestinal side effects
• Depression

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pulmonary Vascular Resistance (PVR) at Three Months	PVR will be measured by right heart catheterization at baseline and 3 months. Change in PVR will be determined by baseline value minus 3 month value.	Change in PVR at 3 mos (Baseline - 3 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change Between Baseline and Three Month in the QIDS-SR Depression Scale	The Quick Inventory of Depressive Symptomatology Self Report (QIDS-SR) depression scale is a questionnaire completed by the patient. Lower scores are better. Scoring can be interpreted as 7 or less: normal, 8-12: mild depression, 13-16 moderate depression, 17-20 moderate to severe depression and >20 severe depression. Results here show the median change between baseline and 3 months, making a positive change in score indicative of improvement. Total minimum score is 0 and the maximum is 27.	Baseline - 3 months (median change)
Change in Six Minute Walk Distance at 3 Months	Six minute walk distance will be measured at baseline and after 3 months of fluoxetine. Change in walk distance (mean and SD) will be reported by taking subtracting baseline values from result at 3 months.	3 months

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: Kelly M Chin, MD, UT Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: July 19, 2009
• First Submitted That Met QC Criteria: July 20, 2009
• First Posted (Estimate): July 21, 2009

Study Record Updates

• Last Update Posted (Actual): June 2, 2020
• Last Update Submitted That Met QC Criteria: May 29, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; Pulmonary Arterial Hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Fluoxetine
• Other Study ID Numbers: STU 052009-009; UL1RR024982 (U.S. NIH Grant/Contract)