Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension (T3PAH)
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|ClinicalTrials.gov Identifier: NCT03528902|
Recruitment Status : Recruiting
First Posted : May 18, 2018
Last Update Posted : January 18, 2020
|Condition or disease||Intervention/treatment||Phase|
|Hypertension Pulmonary Arterial Hypertension Familial Primary Pulmonary Hypertension Primary Pulmonary Hypertension Lung Diseases Tamoxifen Estrogen Receptor Antagonist Hormone Antagonists Estrogens||Drug: Tamoxifen Drug: Placebo Oral Tablet||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Single-center, randomized, double-blind, placebo-controlled Phase II study of 24 subjects with PAH. Eligible subjects will be randomized to treatment with a 1:1 ratio using a permuted-block randomization algorithm.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension|
|Actual Study Start Date :||October 1, 2018|
|Estimated Primary Completion Date :||June 30, 2022|
|Estimated Study Completion Date :||June 30, 2023|
20 mg po TID for 24 weeks
Tamoxifen 20 mg po daily for 24 weeks.
Placebo Comparator: Placebo
Drug: Placebo Oral Tablet
- Transthoracic echocardiogram (ECHO)-based change in the Tricuspid Annular Plane Systolic Excursion (TAPSE) measurement [ Time Frame: 24 weeks ]
Transthoracic echocardiograms (ECHOs) will be performed to measure the TAPSE value prior to Intervention at Week 0, as well as at the end of the study intervention (Week 24). The primary outcome measure will be the change in TAPSE, determined by echocardiogram, from Week 0 to Week 24.
About TAPSE: Tricuspid annular plane systolic excursion (TAPSE) is a parameter of global right ventricular function which describes apex-to-base shortening of the ventricle. It is obtained by transthoracic echocardiogram, which can be performed on a resting subject without sedation in the outpatient setting. TAPSE correlates closely with the right ventricular ejection fraction, and has been determined to be both highly specific and easy to measure.
- Six minute walk test distance (6MWTD) [ Time Frame: 24 weeks ]
Change in 6MWTD from Week 0 to Week 24. The 6-minute walk test distance (6MWTD) is a widely accepted measure of exercise capacity and functional status. The 6MWTD is a clinical and research test obtained in a standardized manner according to American Thoracic Society (ATS) Guidelines.
Briefly, the 6MWT is a sub-maximal exercise test on flat ground that is used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity over time.
- Quality of life will be assessed using the SF36 questionnaire. This will be administered at baseline and 12 and 24 weeks. [ Time Frame: 24 weeks ]
Change in score from Week 0 to Week 24.
Specifically, Quality of life will be assessed using two different accepted questionnaires for pulmonary hypertension patients, the SF36 and emPHasis-10 questionnaires. These will be administered at baseline and 12 and 24 weeks.
- Quality of life will be assessed using emPHasis-10 questionnaire. This will be administered at baseline and 12 and 24 weeks. [ Time Frame: 24 weeks ]Change in score from Week 0 to Week 24.
- Plasma BNP [ Time Frame: 24 weeks ]Change in Plasma BNP levels will be assessed from Week 0 to Week 24 during the study. These measurements are made from the plasma, and will require a blood draw from the research participant.
- HgbA1c [ Time Frame: 24 weeks ]Change in hemoglobin A1c (HgbA1c) levels will be assessed from Week 0 to Week 24 during the study. These measurements are made from the plasma, and will require a blood draw from the research participant.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03528902
|Contact: Shannon Cordell, RNemail@example.com|
|Contact: Alisha Lindsey, RRT, MSHAfirstname.lastname@example.org|
|United States, Tennessee|
|Vanderbilt University Medical Center||Recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: Shannon Cordell, RN 615-343-8277 email@example.com|
|Contact: Errine Garnett, MS 615-343-4252 firstname.lastname@example.org|
|Principal Investigator: Eric D Austin, MD, MSc|
|Principal Investigator: James E Loyd, MD|
|Sub-Investigator: Anna R Hemnes, MD|
|Sub-Investigator: Evan Brittain, MD, MSc|