Safety and Efficacy of Fluoxetine in Pulmonary Arterial Hypertension

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00942708
• Collaborator: National Center for Research Resources (NCRR) (NIH)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 23
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Arterial Hypertension	Drug: Fluoxetine	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy of Fluoxetine in Pulmonary Arterial Hypertension
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Pulmonary Vascular Resistance (PVR) at Three Months [Change in PVR at 3 mos (Baseline - 3 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

1. Change Between Baseline and Three Month in the QIDS-SR Depression Scale [Baseline - 3 months (median change)]

   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.

2. Change in Six Minute Walk Distance at 3 Months [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UT Southwestern Medical Center	Dallas	Texas	United States	75390

Sponsors and Collaborators

• University of Texas Southwestern Medical Center
• National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: Kelly M Chin, MD, UT Southwestern Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT00942708
• Other Study ID Numbers: STU 052009-009; UL1RR024982
• First Posted: Jul 21, 2009
• Last Update Posted: Jun 2, 2020
• Last Verified: May 1, 2020

• Keywords provided by University of Texas Southwestern Medical Center: Pulmonary Arterial Hypertension; Pulmonary Hypertension
• Additional relevant MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension; Fluoxetine

Study Results

Participant Flow

Arm/Group Title	Fluoxetine
Arm/Group Description	In this single arm study, participants begin fluoxetine at 20 mg daily. If tolerated, the dose is increased every 2 weeks as follows: Starting dose: 20 mg daily (week 1-2) Next dose: 40 mg daily (week 3-4) Next dose: 40 mg twice daily (week 5-12) If unable to tolerate uptitration, participants may remain at a lower dose.
Period Title: Overall Study
STARTED	6
COMPLETED	5
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Fluoxetine
Arm/Group Description	Fluoxetine will be added starting at 20 mg and titrated as tolerated to 80 mg daily. Fluoxetine: : Week 1-2 20 mg daily Week 3-4 40 mg daily Week 5-12 40 mg BID
Overall Participants	6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.2 (11.2)
Sex: Female, Male (Count of Participants)
Female	5 83.3%
Male	1 16.7%

Outcome Measures

1. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fluoxetine
Arm/Group Description	Fluoxetine will be started at 20 mg and increased every 2 weeks as tolerated to 80 mg daily. Week 1-2 20 mg daily Week 3-4 40 mg daily Week 5-12 40 mg twice daily
Measure Participants	5
Mean (Standard Deviation) [Wood units]	-0.49 (0.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fluoxetine
	Comments
	Type of Statistical Test	Other
	Comments	Single group evaluation of change in PVR between 12 weeks and baseline (T-test for one group, 2-sided, p<0.05 considered significant)
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	t-test, 1 sided
	Comments

2. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fluoxetine
Arm/Group Description	Fluoxetine will be added starting at 20 mg and titrated as tolerated to 80 mg daily
Measure Participants	5
Median (Full Range) [units on a scale]	1

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All patients completing the 12 week study were analyzed

Arm/Group Title	Fluoxetine
Arm/Group Description	Fluoxetine will be started at 20 mg and increased every 2 weeks as tolerated to 80 mg daily. Week 1-2 20 mg daily Week 3-4 40 mg daily Week 5-12 40 mg twice daily
Measure Participants	5
Mean (Standard Deviation) [meters]	10 (48)

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Fluoxetine
Arm/Group Description	Fluoxetine will be added starting at 20 mg and titrated as tolerated to 80 mg daily. Fluoxetine: Week 1-2 20 mg daily Week 3-4 40 mg daily Week 5-12 40mg BID
All Cause Mortality
	Fluoxetine
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Serious Adverse Events
	Fluoxetine
	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)
Cardiac disorders
Chest pain or tightness	1/6 (16.7%)	1
Product Issues
Line malfunction	1/6 (16.7%)	6
Other (Not Including Serious) Adverse Events
	Fluoxetine
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Cardiac disorders
Syncope	1/6 (16.7%)	1
Lightheadedness	1/6 (16.7%)	1
Chest pain	1/6 (16.7%)	1
Gastrointestinal disorders
Nausea	2/6 (33.3%)	2
Heartburn	1/6 (16.7%)	1
Diarrhea	1/6 (16.7%)	1
Indigestion	1/6 (16.7%)	1
Reflux	1/6 (16.7%)	1
Infections and infestations
Cold	1/6 (16.7%)	1
Nervous system disorders
Drowsiness	1/6 (16.7%)	1
Shaking	1/6 (16.7%)	1
Yawning	1/6 (16.7%)	1
Lack of concentration	1/6 (16.7%)	1
Psychiatric disorders
Nervousness	1/6 (16.7%)	1
Anxiety	1/6 (16.7%)	1
Respiratory, thoracic and mediastinal disorders
Shortness of breath	1/6 (16.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.