Identification of Heritable CTEPH

Identification and Molecular Characterization of Heritable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Some patients who have blood clots come down with a life-threatening condition known as Chronic Thromboembolic Pulmonary Hypertension (CTEPH), which is high blood pressure only in the arteries of the lungs. This study seeks to understand more about the genetics causes of CTEPH by obtaining blood samples and examining family histories.

Study Overview

• Status: Recruiting
• Conditions: Chronic Thromboembolic Pulmonary Hypertension
• Intervention / Treatment: Other: Blood Draw

Detailed Description

This project proposes to identify a cohort of Utah patients with CTEPH, and to perform a comprehensive analysis of family history and CTEPH risk factors in these patients, and in controls with acute pulmonary embolism (PE) and pulmonary arterial hypertension (PAH). Detailed family history interviews will be performed with all patients, and all enrolled patients will provide a blood sample for thrombophilia testing and for gene sequencing with the goal of identifying novel genetic variants that contribute to CTEPH risk.

• Study Type: Observational
• Enrollment (Anticipated): 260

Contacts and Locations

Study Locations

• United States
  • Utah
    • Murray, Utah, United States, 84107
      • Recruiting
      • Intermountain Medical Center
      • Principal Investigator: Mark Dodson, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with CTEPH will be recruited and enrolled at Intermountain Healthcare, also from outside of Intermountain Healthcare, for example at the University of Utah (following IRB approval there) and at national conferences.

Description

Inclusion Criteria:

• CTEPH cohort:

  1. Confirmed CTEPH based on having undergone PEA surgery.
  2. Strongly suspected CTEPH based on right heart catheterization data showing mPAP>26 and PCWP<15, and imaging demonstrating chronic thromboembolic disease (either ventilation/perfusion scan, CT pulmonary angiography, or conventional pulmonary angiography).

• PE cohort:

  1. PE diagnosed by CT pulmonary angiography or ventilation/perfusion scan within the preceding 24 months.
  2. No evidence of PH at the time of enrollment (based on absence of dyspnea, exertional chest pain, or exertional presyncope on history, lack of physical exam findings of PH or right heart failure, and lack of signs of PH on objective data including echocardiography and/or right heart catheterization).
  3. No evidence of chronic thromboembolic disease at the time of enrollment (based on chronic appearing thrombus on CT pulmonary angiography or conventional pulmonary angiography, or based on prior high probability ventilation/perfusion scan showing a similar pattern of perfusion defects).

• PAH cohort:

  1. Diagnosis of group 1 PAH.
  2. Prior normal or low probability ventilation/perfusion scan.
  3. No reported history of prior VTE events.
  4. If available, all prior evaluations for VTE (including CT pulmonary angiography and Doppler ultrasound exams) must also be negative.

Exclusion Criteria:

• Under the age of 18

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Chronic Thromboembolic Pulmonary Hypertension (CTEPH)	Other: Blood Draw
Pulmonary Embolism (PE)	Other: Blood Draw
Pulmonary Arterial Hypertension (PAH)	Other: Blood Draw

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rates of family history of VTE in relatives of CTEPH patients compared to PE and PAH patients in Intermountain populations	through study completion, approximately 18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Characteristics of familial and, apparently, sporadic CTEPH in Intermountain populations	through study completion, approximately 18 months
Estimates of prevalence of familial CTEPH in Intermountain populations	through study completion, approximately 18 months
Heritability and penetrance patterns of familial CTEPH	through study completion, approximately 18 months
Discovery and validation of genetic polymorphisms present in familial CTEPH patients	through study completion, approximately 18 months
Identification of gene pathways that may be relevant to the development of CTEPH after actue PE	through study completion, approximately 18 months

Collaborators and Investigators

• Sponsor: Intermountain Health Care, Inc.
• Investigators: Principal Investigator: Mark Dodson, MD, Intermountain Health Care, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 25, 2013
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: May 24, 2018
• First Submitted That Met QC Criteria: July 5, 2018
• First Posted (ACTUAL): July 9, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 18, 2022
• Last Update Submitted That Met QC Criteria: October 17, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary
• Other Study ID Numbers: 1024723

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No