Fluoxetine in Pulmonary Arterial Hypertension (PAH) Trial

NCT03638908 | Completed Phase 2 Results DMC

• 2 other identifiers: NIKK23STU 082013-045
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline and Week 24

Secondary Outcomes (1)

• 5-HIAA (HYDROXYINDOLE ACETIC ACID) Level

  Baseline and Week 24

Other Outcomes (8)

• Markers of Platelets and Endothelial Activation in PAH.

  Baseline and Week 24

• Exercise Capacity

  baseline and 24

• Functional Class

  baseline and 24

Study Arms (1)

Fluoxetine

OTHER

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

Drug: Fluoxetine

Interventions

Fluoxetine DRUG

Fluoxetine

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Fluoxetine

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Kelly Chin, MD
• Organization: UTSouthwestern medical center

kelly.chin@utsouthwestern.edu

2146456493

Study Officials

• Kelly Chin, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2018
• First Posted: August 20, 2018
• Study Start: November 1, 2013
• Primary Completion: May 1, 2017
• Study Completion: December 1, 2018
• Last Updated: June 26, 2020
• Results First Posted: October 7, 2019

Record last verified: 2020-06

Locations

US (1)