Fluoxetine in Pulmonary Arterial Hypertension (PAH) Trial

Phase 2

Completed

• Conditions: Pulmonary Arterial Hypertension
• Interventions: Drug: Fluoxetine

• Registration Number: NCT03638908
• Lead Sponsor: University of Texas Southwestern Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-11
• Primary Completion: 2017-05
• Study First Submitted: 2018-07-12
• Study First Submitted QC: 2018-08-17
• Study First Posted: 2018-08-20
• Study Completion: 2018-12
• Results First Submitted: 2019-01-15
• Results First Submitted QC: 2019-09-13
• Results First Posted: 2019-10-07
• Status Verified: 2020-06
• Last Update Submitted: 2020-06-24
• Last Update Posted: 2020-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

1. 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
2. Age 16-80
3. WHO Functional Class II or III
4. Right Heart Catheterization within 3 weeks of study entry with mPAP ≥ 25 mmHg, wedge ≤ 15 mmHg, and PVR ≥ 3 Wood units.
5. Contraception use, (-) urine pregnancy test, not breast feeding (women of childbearing potential)
6. 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

7. WHO Functional Class IV or listed for lung transplant

8. Moderate or greater obstructive lung disease: FEV1/FVC <70% and FEV1 <60%

9. 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)

10. 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%

11. Depression

12. Severe liver, renal or other medical or physical disease preventing completion of the study procedures

13. Use of antidepressants within 3 months

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fluoxetine	Fluoxetine	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

Primary Outcome Measures

Name	Time	Method
Pulmonary Vascular Resistance (PVR)	Baseline and Week 24	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

Name	Time	Method
5-HIAA (HYDROXYINDOLE ACETIC ACID) Level	Baseline and Week 24	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

Trial Locations

Locations (1)

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States