Safety and Efficacy of Fluoxetine in Pulmonary Arterial Hypertension
Primary Purpose
Pulmonary Arterial Hypertension
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fluoxetine
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring Pulmonary Arterial Hypertension, Pulmonary Hypertension
Eligibility 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
Sites / Locations
- UT Southwestern Medical Center
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Fluoxetine
Arm Description
Fluoxetine will be added starting at 20 mg and titrated as tolerated to 80 mg daily.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT00942708
First Posted
July 19, 2009
Last Updated
May 29, 2020
Sponsor
University of Texas Southwestern Medical Center
Collaborators
National Center for Research Resources (NCRR)
1. Study Identification
Unique Protocol Identification Number
NCT00942708
Brief Title
Safety and Efficacy of Fluoxetine in Pulmonary Arterial Hypertension
Official Title
Safety and Efficacy of Fluoxetine in Pulmonary Arterial Hypertension
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
September 2009 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
August 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Texas Southwestern Medical Center
Collaborators
National Center for Research Resources (NCRR)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will evaluate the safety, tolerability and efficacy of open-label fluoxetine for three months among patients with pulmonary arterial hypertension.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
Keywords
Pulmonary Arterial Hypertension, Pulmonary Hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fluoxetine
Arm Type
Other
Arm Description
Fluoxetine will be added starting at 20 mg and titrated as tolerated to 80 mg daily.
Intervention Type
Drug
Intervention Name(s)
Fluoxetine
Other Intervention Name(s)
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
Intervention Description
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
Primary Outcome Measure Information:
Title
Change in Pulmonary Vascular Resistance (PVR) at Three Months
Description
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.
Time Frame
Change in PVR at 3 mos (Baseline - 3 months)
Secondary Outcome Measure Information:
Title
Change Between Baseline and Three Month in the QIDS-SR Depression Scale
Description
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.
Time Frame
Baseline - 3 months (median change)
Title
Change in Six Minute Walk Distance at 3 Months
Description
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.
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kelly M Chin, MD
Organizational Affiliation
UT Southwestern Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy of Fluoxetine in Pulmonary Arterial Hypertension
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