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Fluoxetine in Pulmonary Arterial Hypertension (PAH) Trial (PAH)

Primary Purpose

Pulmonary Arterial Hypertension

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Fluoxetine

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension

Eligibility Criteria

16 Years - 80 Years (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

WHO Group I PAH subtypes of idiopathic PAH and PAH associated with drugs / toxins, connective tissue disease, repaired congenital heart disease and unrepaired atrial septal defect
Age 16-80
WHO Functional Class II or III
Right Heart Catheterization within 3 weeks of study entry with mPAP ≥ 25 mmHg, wedge ≤ 15 mmHg, and PVR ≥ 3 Wood units.
Contraception use, (-) urine pregnancy test, not breast feeding (women of childbearing potential)
One or more approved PAH therapies for ≥ 3 months, no change in dose for 1 month (endothelin-1 antagonist, phosphodiesterase-5 inhibitor, prostacyclin / prostacyclin analog). Novel approved therapies in one of the three existing classes will also be acceptable as background therapy if they become available during the course of the study; other medication classes are excluded
Exclusion Criteria:
WHO Functional Class IV or listed for lung transplant
Moderate or greater obstructive lung disease: FEV1/FVC <70% and FEV1 <60%
Moderate or greater restrictive lung disease: TLC or FVC <60% (if 50-60%: OK if TLC or FVC ≥50% + PFT stable x1 year + CT with no more than mild lung disease)
Other cause for pulmonary hypertension: all other WHO group I diseases (including but not limited to liver disease, HIV), and WHO Groups II-V (i.e. left heart disease, lung disease, chronic PE and miscellaneous causes)24.
1. High probability VQ or positive CTA
2. Left ventricular ejection fraction <40%
Depression
Severe liver, renal or other medical or physical disease preventing completion of the study procedures
Use of antidepressants within 3 months

Sites / Locations

UT Southwestern Medical Center

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Fluoxetine

Arm Description

Dosing will be Week 1-4: 20 mg daily Week 5-8: 40 mg daily Week 9-12: 60 mg daily Week 13-24: 80 mg daily

Outcomes

Primary Outcome Measures

Pulmonary Vascular Resistance (PVR)

Change in PVR between baseline and follow-up will be utilized. PVR is calculated as [(Pulmonary Artery mean - wedge) / Fick Cardiac Output]. Fick CO will be used in computing PVR over thermodilution because Fick appears to have greater precision (but not accuracy). The calculation of PVR above is measured in woods unit. Change is derived by getting the difference between baseline and week 24 PVR (Week 24 minus Baseline). mean is then computed by getting the average of the change

Secondary Outcome Measures

5-HIAA (HYDROXYINDOLE ACETIC ACID) Level

Urine for spot urine 5-HIAA will be collected at baseline and Week 24. Subjects will be on diet restriction 72 hours prior to urine collection. Sample will be the first morning urine on the visit day. Sample will be brought to site and then sent to affiliate outside laboratory for processing. 5HIAA results are expressed as a ratio to creatinine excretion in the unit "mg/g creatinine" Change 5-HIAA is derived by getting the difference between baseline and week 24 5HIAA results (Week 24 minus Baseline). mean is then computed by getting the average of the change

Full Information

NCT ID

NCT03638908

First Posted

July 12, 2018

Last Updated

June 24, 2020

Sponsor

University of Texas Southwestern Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT03638908

Brief Title

Fluoxetine in Pulmonary Arterial Hypertension (PAH) Trial

Acronym

PAH

Official Title

A Phase 2, Open-label, Clinical Trial of Fluoxetine, a Selective Serotonin Reuptake Inhibitor, in the Treatment of Pulmonary Arterial Hypertension

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Completed

Study Start Date

November 2013 (undefined)

Primary Completion Date

May 2017 (Actual)

Study Completion Date

December 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Texas Southwestern Medical Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This protocol describes an open-label phase 2 clinical trial of fluoxetine in PAH looking at change in pulmonary vascular resistance (PVR) as the primary endpoint. In this open-label clinical trial, 18 patients with pulmonary arterial hypertension will be given fluoxetine for 24 weeks. A Right Heart Catheterization will be performed at baseline and 24 weeks. Change in PVR will be the primary endpoint; other hemodynamic endpoints, quality of life, QIDS-SR depression scale, functional class and six-minute walk distance will also be evaluated. Primary Hypothesis: Fluoxetine treatment for 24 weeks will lead to significantly lower pulmonary vascular resistance in 18 patients with PAH in patients treated in an open-label clinical trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pulmonary Arterial 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

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Fluoxetine

Arm Type

Other

Arm Description

Dosing will be Week 1-4: 20 mg daily Week 5-8: 40 mg daily Week 9-12: 60 mg daily Week 13-24: 80 mg daily

Intervention Type

Drug

Intervention Name(s)

Fluoxetine

Primary Outcome Measure Information:

Title

Pulmonary Vascular Resistance (PVR)

Description

Time Frame

Baseline and Week 24

Secondary Outcome Measure Information:

Title

5-HIAA (HYDROXYINDOLE ACETIC ACID) Level

Description

Time Frame

Baseline and Week 24

Other Pre-specified Outcome Measures:

Title

Markers of Platelets and Endothelial Activation in PAH.

Description

About 20ml blood will be obtained for plasma and serum at Baseline and Week 24. This will be placed in a red-top tube (serum, at least 1 ml) and blue-top tube. For the plasma tests, a plasma volume of 750 microL is required. Samples will be sent together, as a batch of 50 is required, on dry ice via overnight courier. Plasma will be obtained by drawing blood into a blue-top citrated tube, inverting the tube 6 times, and then centrifuging at 2000g for 10 minutes. The platelet poor plasma will be drawn off, and then re-centrifuged for 10 minutes before freezing.

Time Frame

Baseline and Week 24

Title

Exercise Capacity

Description

Exercise capacity will be measure using the 6-minute walk test. Data collected at baseline and 24 were analyzed. The test will follow the ATS guidelines for 6MWT at all time.

Time Frame

baseline and 24

Title

Functional Class

Description

Functional class will be measured using the WHO functional class assessment. This is graded from WHO FC I to FC IV. Assessment will be completed by an investigator on the study at every visit.

Time Frame

baseline and 24

Title

Quick Inventory of Depressive Symptomatology

Description

Patient reported outcome will be assessed using the Quick Inventory of Depressive Symptomatology (16-Item) (Self-Report) (QIDS-SR16) completed at baseline, week 12 and Week 24; baseline and week 24 reported. Each question is scored from minimum of 0 to a maximum of 3; total score ranges from 0 to 42. With zero being better outcome and 42 being severe outcome

Time Frame

baseline and Week 24.

Title

Patient Global Impression of Severity - Symptoms (PGIS)

Description

PGIS questionnaire will be administered for global assessment of severity. This questionnaire is categorical and measures outcome from "none" being best outcome to "severe" being the worst outcome

Time Frame

baseline

Title

Clinician Global Impression of Severity - Symptoms (CGIS)

Description

Global assessment of severity will be determined using Clinician global impression of severity - symptoms (CGIS). This questionnaire is categorical and measures outcome from "none" being best outcome to "severe" being the worst outcome

Time Frame

Week 12 and Week 24.

Title

Short Form 36

Description

Patient reported outcome will also be assessed using SF-36 completed at baseline, Week 12 and Week 24. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. The eight sections are: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health

Time Frame

baseline, Week 12 and Week 24.

Title

Clinician Global Impression of Change (CGI-change)

Description

CGI-change questionnaire will be completed for global assessment of severity. This questionnaire is categorical and measures outcome from "very much better" being best outcome to "very much worse" being the worst outcome

Time Frame

Weeks 12 and 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

16 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: WHO Group I PAH subtypes of idiopathic PAH and PAH associated with drugs / toxins, connective tissue disease, repaired congenital heart disease and unrepaired atrial septal defect Age 16-80 WHO Functional Class II or III Right Heart Catheterization within 3 weeks of study entry with mPAP ≥ 25 mmHg, wedge ≤ 15 mmHg, and PVR ≥ 3 Wood units. Contraception use, (-) urine pregnancy test, not breast feeding (women of childbearing potential) One or more approved PAH therapies for ≥ 3 months, no change in dose for 1 month (endothelin-1 antagonist, phosphodiesterase-5 inhibitor, prostacyclin / prostacyclin analog). Novel approved therapies in one of the three existing classes will also be acceptable as background therapy if they become available during the course of the study; other medication classes are excluded Exclusion Criteria: WHO Functional Class IV or listed for lung transplant Moderate or greater obstructive lung disease: FEV1/FVC <70% and FEV1 <60% Moderate or greater restrictive lung disease: TLC or FVC <60% (if 50-60%: OK if TLC or FVC ≥50% + PFT stable x1 year + CT with no more than mild lung disease) Other cause for pulmonary hypertension: all other WHO group I diseases (including but not limited to liver disease, HIV), and WHO Groups II-V (i.e. left heart disease, lung disease, chronic PE and miscellaneous causes)24. High probability VQ or positive CTA Left ventricular ejection fraction <40% Depression Severe liver, renal or other medical or physical disease preventing completion of the study procedures Use of antidepressants within 3 months

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kelly 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

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Fluoxetine in Pulmonary Arterial Hypertension (PAH) Trial

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