Tamoxifen Therapy to Treat Pulmonary Arterial Hypertension

NCT03528902 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 180241
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  24 weeks

Secondary Outcomes (3)

• Six Minute Walk Test Distance (6MWTD)

  24 weeks

• Quality of Life Will be Assessed Using the SF36 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks.

  24 weeks

• Quality of Life Will be Assessed Using emPHasis-10 Questionnaire. This Will be Administered at Baseline and 12 and 24 Weeks.

  24 weeks

Other Outcomes (2)

• Plasma BNP

  24 weeks

• HgbA1c

  24 weeks

Study Arms (2)

Tamoxifen

EXPERIMENTAL

20 mg po TID for 24 weeks

Drug: Tamoxifen

Placebo

PLACEBO COMPARATOR

Placebo arm

Drug: Placebo Oral Tablet

Interventions

Tamoxifen DRUG

Tamoxifen 20 mg po daily for 24 weeks.

Tamoxifen

Placebo Oral Tablet DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Lung Diseases

Interventions

Tamoxifen

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hypertension, Pulmonary; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Research Programs Manager
• Organization: Vanderbilt University Medical Center

ph_research@vumc.org

615-322-4703

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Model Details: 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.

Study Record Dates

• First Submitted: March 21, 2018
• First Posted: May 18, 2018
• Study Start: October 1, 2018
• Primary Completion: June 14, 2023
• Study Completion: June 14, 2023
• Last Updated: December 5, 2024
• Results First Posted: December 5, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: 2 years after study completion.
• Access Criteria: Criteria include: * detailed written description of the project for which the data would be used. * acknowledge in any publication resulting from the data, the source of the data, crediting the program support. * agree to submit all papers or reports submitted for publication to the PI for review prior to submission.

Locations

US (1)