HypertensionPhase 2T3PAHNCT03528902
Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension
A Phase 2 study testing Tamoxifen in people with Hypertension and Pulmonary Arterial Hypertension, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertension, Pulmonary Arterial Hypertension, Familial Primary Pulmonary Hypertension
- What is being tested?
- Tamoxifen
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2018to 14 Jun 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Previous documentation of mean pulmonary artery pressure greater than or equal to 25 mm Hg with a pulmonary capillary wedge pressure (or left ventricular end-diastolic pressure) less than or equal to15 mm Hg and PVR greater than or equal to 3 WU at any time before study entry, consistent Group 1 PAH classified by accepted international classification.
- Diagnosis of PAH which is idiopathic, heritable, drug- or toxin-induced, or associated with connective tissue disease.
- Age 18 years and older.
- WHO Functional Class I, II, or III status.
- Ability to perform a six minute walk test without significant limitations in musculoskeletal function or coordination, with distance greater than or equal to 150m and less than or equal to 550m.
- Informed consent.
Who cannot join
- Current treatment with estrogen, progesterone, or any form of sex hormone therapy.
- Current treatment with anti-sex hormone therapy (e.g., anastrozole, fulvestrant, tamoxifen, leuprolide acetate (luporon) or other centrally-acting hormone agents.
- WHO Functional Class IV status.
- History of, or current, breast, uterine, ovarian, or testicular cancer.
- Current pregnancy, or prior pregnancy within 3 months of enrollment.
- Initiation of PAH therapy (prostacyclin analogues, endothelin-1 receptor antagonists, phosphodiesterase-5 inhibitors, riociguat, selexipag) within three months of enrollment; the dose must be stable for at least three months prior to Baseline Visit. Of note, PAH therapy, including diuretics, which is stopped and then restarted or has dose changes which are not related to initiation and up titration will be allowed within 3 months prior to the Baseline Visit, and during the trial for subjects.
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- History of thromboembolic event.
- Hospitalized or acutely ill.
- Renal failure (creatinine over 2.0).
- Hypercalcemia.
- Severe osteoporosis (t score < -2.0 OR t score < -2.5 if on bone modifying treatment).
- Current or recent (< 3 months) chronic heavy alcohol consumption.
- Enrollment in a clinical trial or concurrent use of another investigational drug (non FDA approved) or device therapy within 30 days of screening visit.
- Enrollment in any pharmacologic clinical trial within one month of screening.
- Due to potential drug interactions with tamoxifen, subjects using bosentan (CYP3A4) or selexipag (CYP2C8) will be excluded.
- Due to the concerns of pregnancy during PAH and with tamoxifen use, subjects will be excluded who do not use at least two forms of contraception (e.g., IUD plus the use of a barrier contraceptive method).
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
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.
Read the 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
- Being tested
- Tamoxifen, Placebo Oral Tablet
- Medical subject headings
- Hypertension, Pulmonary Arterial Hypertension, Familial Primary Pulmonary Hypertension, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TamoxifenDrug
Tamoxifen 20 mg po daily for 24 weeks.
Placebo Oral TabletDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Tamoxifen | Experimental | 20 mg po TID for 24 weeks Receives: Drug: Tamoxifen |
| Placebo | Placebo comparator | Placebo arm Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Transthoracic Echocardiogram (ECHO)-Based Change in the Tricuspid Annular Plane Systolic Excursion (TAPSE) Measurement
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.
Measured: 24 weeks
Secondary outcomes (3)
Six Minute Walk Test Distance (6MWTD)
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.
Measured: 24 weeks
Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 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 questionnaires. These will be administered at baseline and 12 and 24 weeks. Note that all items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.
Measured: 24 weeks
Quality of Life Will be Assessed Using emPHasis-10 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks.
This will be administered at baseline and 12 and 24 weeks. Change in score from Week 0 to Week 24 will be reported. emPHasis-10 scores range from 0 to 50, higher scores indicate worse quality of life
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2018
- Study start1 Oct 2018
- Primary completion14 Jun 2023
- Study completion14 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eric Austin, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03528902
- Sponsor's protocol ID
- 180241
- Acronym
- T3PAH
- Status last verified
- Nov 2024
- First submitted
- 21 Mar 2018
- Last updated
- 5 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Since the data that will be produced involves patients with a disease process that is much in need of new treatment options and the investigators agree that data sharing is essential for expedited translation of research results into patient treatment options. A detailed data sharing plan is in place and available upon request. In brief: It is our plan to make data available at the time it is accepted for publication of the main findings from the final dataset through the use of a data enclave of our own design that would restrict our Data Analyst from sharing any information that would breach participant confidentiality. Potential researchers will contact the PI to discuss specific needs and how the data will be utilized. A formal approval process is in place to evaluate and complete such requests.
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT03528902
- Acronym / sponsor ID
- T3PAH / 180241
- Conditions
- Hypertension, Pulmonary Arterial Hypertension, Familial Primary Pulmonary Hypertension, Primary Pulmonary Hypertension, Lung Diseases, Tamoxifen
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- 1 Oct 2018 (actual)
- Primary completion
- 14 Jun 2023 (actual)
- Study completion
- 14 Jun 2023 (actual)
- First posted
- 18 May 2018 (actual)
- Results
- Posted 5 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Tamoxifen | Experimental | Drug: Tamoxifen20 mg po TID for 24 weeks |
| Placebo | Placebo comparator | Drug: Placebo Oral TabletPlacebo arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Previous documentation of mean pulmonary artery pressure greater than or equal to 25 mm Hg with a pulmonary capillary wedge pressure (or left ventricular end-diastolic pressure) less than or equal to15 mm Hg and PVR greater than or equal to 3 WU at any time before study entry, consistent Group 1 PAH classified by accepted international classification.
- Diagnosis of PAH which is idiopathic, heritable, drug- or toxin-induced, or associated with connective tissue disease.
- Age 18 years and older.
- WHO Functional Class I, II, or III status.
- Ability to perform a six minute walk test without significant limitations in musculoskeletal function or coordination, with distance greater than or equal to 150m and less than or equal to 550m.
Key exclusion criteria (16 listed)
- Current treatment with estrogen, progesterone, or any form of sex hormone therapy.
- Current treatment with anti-sex hormone therapy (e.g., anastrozole, fulvestrant, tamoxifen, leuprolide acetate (luporon) or other centrally-acting hormone agents.
- WHO Functional Class IV status.
- History of, or current, breast, uterine, ovarian, or testicular cancer.
- Current pregnancy, or prior pregnancy within 3 months of enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TamoxifenTamoxifen 20 mg po daily for 24 weeks. | Drug | Tamoxifen |
| Placebo Oral TabletPlacebo | Drug | Placebo |
Primary outcome
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.
3 secondary outcomes
Six Minute Walk Test Distance (6MWTD)
Time frame: 24 weeks
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Since the data that will be produced involves patients with a disease process that is much in need of new treatment options and the investigators agree that data sharing is essential for expedited translation of research results into patient treatment options. A detailed data sharing plan is in place and available upon request. In brief: It is our plan to make data available at the time it is accepted for publication of the main findings from the final dataset through the use of a data enclave of our own design that would restrict our Data Analyst from sharing any information that would breach participant confidentiality. Potential researchers will contact the PI to discuss specific needs and how the data will be utilized. A formal approval process is in place to evaluate and complete such requests.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tamoxifen in people with Hypertension and Pulmonary Arterial Hypertension, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Transthoracic Echocardiogram (ECHO)-Based Change in the Tricuspid Annular Plane Systolic Excursion (TAPSE) Measurement (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2024.