NCT03528902

Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Vanderbilt University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The main purpose of this clinical trial is to examine the feasibility and effects of tamoxifen in subjects with pulmonary arterial hypertension (PAH). The study will evaluate how well the drug is tolerated, and its impact on functional condition and selected biomarkers. Changes in tricuspid annular plane systolic excursion (TAPSE) and other parameters determined by transthoracic echocardiography will be evaluated as well as changes in additional metrics such as six minute walk test distance, quality of life assessments, and hormone levels.

Detailed description

Pulmonary arterial hypertension (PAH) is characterized by progressive loss of function by the pulmonary vascular bed due to a variety of factors including obliterative vascular lesions, vasoconstriction, and thrombotic occlusion of the pulmonary arteries. Ultimately, right-sided heart failure ensues with severe limitation of exercise and eventual progression to death or lung transplantation. While there are multiple FDA-approved therapies for PAH representing 3 major pathways of interest, no treatments are curative, and have additional limitations including high expense, multiple side effects, and dosing inconveniences. The strongest established risk factor for the progressively fatal disease pulmonary arterial hypertension (PAH) is female sex (\~3:1 female:male ratio). We and others have found higher circulating estrogen levels, and enhanced estrogen signaling, in PAH patients. Preclinical work by our group and others supports the concept that anti-estrogen therapy, is effective for both prevention and treatment in PAH. Recent and ongoing clinical studies are underway to assess these approaches in humans, including a recent study demonstrating the safety of estrogen reduction in postmenopausal women. Tamoxifen is the most commonly used selective estrogen receptor modulator (SERM). Due to its extensive use in humans for over three decades, it has an excellent safety profile and its long-term sequelae are well characterized. Furthermore, it is a generic drug which has been FDA-approved for treatment and prevention of breast cancer, particularly those with estrogen receptor-positive neoplasms. To help to determine whether tamoxifen may be a safe and effective treatment for PAH in women and men, we will conduct a single-center, randomized, double-blind, placebo-controlled Phase II study of subjects with PAH. All subjects will also be treated with background standard of care therapy at the discretion of their PAH care physician.

Conditions

• Hypertension
• Pulmonary Arterial Hypertension
• Familial Primary Pulmonary Hypertension
• Primary Pulmonary Hypertension
• Lung Diseases
• Tamoxifen
• Estrogen Receptor Antagonist
• Hormone Antagonists
• Estrogens

Interventions

Type	Name	Description
DRUG	Tamoxifen	Tamoxifen 20 mg po daily for 24 weeks.
DRUG	Placebo Oral Tablet	Placebo

Timeline

• Start date: 2018-10-01
• Primary completion: 2023-06-14
• Completion: 2023-06-14
• First posted: 2018-05-18
• Last updated: 2024-12-05
• Results posted: 2024-12-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study