Clinical trial NCT03638908: Fluoxetine in Pulmonary Arterial Hypertension (PAH) Trial
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2018-08-20
Enrollment: 8
Sex: ALL
Minimum age (years): 16
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pulmonary Vascular Resistance (PVR)
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: 5-HIAA (HYDROXYINDOLE ACETIC ACID) Level
timeFrame: Baseline and Week 24
Other outcomes:
measure: Markers of Platelets and Endothelial Activation in PAH.
timeFrame: Baseline and Week 24
measure: Exercise Capacity
timeFrame: baseline and 24
measure: Functional Class
timeFrame: baseline and 24
measure: Quick Inventory of Depressive Symptomatology
timeFrame: baseline and Week 24.
measure: Patient Global Impression of Severity - Symptoms (PGIS)
timeFrame: baseline
measure: Clinician Global Impression of Severity - Symptoms (CGIS)
timeFrame: Week 12 and Week 24.
measure: Short Form 36
timeFrame: baseline, Week 12 and Week 24.
measure: Clinician Global Impression of Change (CGI-change)
timeFrame: Weeks 12 and 24
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Kelly Chin, MD
role: PRINCIPAL_INVESTIGATOR
References: