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This is a multi-center prospective cohort study of patients with first-episode deep venous thrombosis and pulmonary embolism.
Subjects will be identified from the clinical setting and approached to participate in this observational study where participants will be enrolled at 3 different sites and referred from several more sites and have: cardiopulmonary exercise testing and pulmonary function testing at The Institute of Exercise and Environmental Medicine (IEEM), UTSW Exercise Facility, Cardiac MRI and MRI for pulmonary perfusion at Children's Medical Center and MR Spectroscopy and MR for Muscle Perfusion at the Advanced Imaging Research Center (AIRC) performed in Dallas over a 3 day research visit at week 12 and Month 12. Blood is collected for biomarkers at these visits and multiple questionnaires are completed by participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Participants with Pulmonary Embolism | The target accrual is based on the primary endpoint (exercise intolerance and dyspnea on exertion). To achieve adequate power and precision in the primary analysis, the target enrollment is 80 children. Both males and females of all races and ethnic groups are eligible for this study. |
| |
| Control Group | A positive control group that has not had pulmonary embolism (PE) but is prescribed physical activity restrictions expected to produce a similar deconditioning effect as patients with PE will be enrolled from UT Southwestern only (cohort 1) or children who are no prescribed physical activity restrictions and are otherwise considered healthy (cohort 2). The target accrual of the positive control group is based on feasibility and availability of funds and will be limited to 25 controls. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood draw (Visit 1) | Diagnostic Test | Labs will be drawn at Visit 1, also referred to as screening (within 60 days of diagnosis) with the standard of care labs drawn. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in exercise capacity | Measured objectively by peak oxygen uptake (VO2) as a percent predicted based on ml/min/kg of lean body mass during cardiopulmonary exercise testing (CPET) | 3 months and 12 months post-diagnosis |
| Change in dyspnea on exertion (DOE) | measured using Borg questionnaire and defined as a mean difference of > 1 between those with and without exercise intolerance at the end of the warm-up and submaximal work rates during CPET | 3 months and 12 months post-diagnosis |
| Measure | Description | Time Frame |
|---|---|---|
| Change in cardiac maladaptation | Measured as ventriculo-arterial coupling ratio in response to exercise (change in Ea/Emax from rest to peak intensity exercise) during exercise cardiac magnetic resonance imaging (MRI) | 3 months and 12 months post-diagnosis |
| Change in pulmonary/ventilatory limitations |
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Inclusion Criteria:
Exclusion Criteria:
Additional exclusion criteria for participants with PE:
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Study population will include children (defined as persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted), and patients (defined as individuals in a clinical setting with whom there is a treatment relationship).
Participants must meet the eligibility criteria in order to participate in this trial.
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| Name | Affiliation | Role |
|---|---|---|
| Ayesha Zia, MD, MSCS | University of Texas Southwestern Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Arkansas Childrens Research Institute (ACRI) | Little Rock | Arkansas | 72202 | United States | ||
| Johns Hopkins All Childrens Hospital |
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| Label | URL |
|---|---|
| FUVID Website | View source |
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Research Biomarkers: blood for inflammatory markers, thrombin generation and fibrinolysis assays are required for all participants. Research Blood for DNA/RNA only collected for those participants who consent to genetic material.
| Blood draw (Visits 2 and 3) | Diagnostic Test | Labs will be drawn at Visit 2 (12 weeks post-diagnosis with a range of 10-16 weeks) and Visit 3 (12 months ± 30 days) for research purposes only and will be collected at Children's Medical Center and processed at UT Southwestern Medical Center. |
|
Measured as VE/VCO2 in participants with and without exercise intolerance during cardiopulmonary testing |
| 3 months and 12 months post-diagnosis |
| Change in muscle metabolic aberrations | Measured by % phosphocreatine (PCr) depletion (Δ %PCr) during exercise using 31P magnetic resonance spectroscopy on 7 Tesla in participants with and without exercise intolerance | 3 months and 12 months post-diagnosis |
| Change in pulmonary vascular obstruction score in participants with and without exercise intolerance (Quantitative assessment) | Quantitative Assessment: Measured using Qanadli Index scale (range 0-40; 0=minimum score and 40=maximum score) at pulmonary embolism diagnosis and 3 months post-diagnosis. | At diagnosis, 3 months and 12 months post-diagnosis |
| Change in pulmonary vascular obstruction score in participants with and without exercise intolerance (Qualitative assessment) | Qualitative Assessment: Measured using pulmonary perfusion maps at diagnosis, 3 and 12 months post-diagnosis. Since qualitative, there are no minimum or maximum values. | At diagnosis, 3 months and 12 months post-diagnosis |
| Change in calf muscle perfusion and venous flow in participants with and without exercise intolerance and between affected and non-affected extremity | Measured using extremity arterial spin labelling on 7 Tesla MRI | 3 months and 12 months post-diagnosis |
| Change in dyspnea ratings using Dalhousie Pictorial Scale | Measured at rest, fatigue, and post-exercise in participants with and without exercise intolerance Dalhousie Pictorial Scale measuring Dyspnea and Perceived Exertion (minimum score=4; maximum score=28; higher score means worse dyspnea) | 3 months and 12 months post-diagnosis |
| Change in dyspnea ratings using Borg Dyspnea Scale | Measured at rest, fatigue, and post-exercise in participants with and without exercise intolerance Borg Dyspnea Scale (minimum score=0; maximum score=10; higher score means worse dyspnea) | 3 months and 12 months post-diagnosis |
| Change in dyspnea ratings using Dyspnoea-12 Scale | Measured at rest, fatigue, and post-exercise in participants with and without exercise intolerance Dyspnoea-12 Scale (minimum score=0; maximum score=36; higher score means worse dyspnea) | 3 months and 12 months post-diagnosis |
| Change in dyspnea ratings using Modified Medical Research Council Dyspnea Scale | Measured at rest, fatigue, and post-exercise in participants with and without exercise intolerance Modified Medical Research Council Dyspnea Scale (minimum score=0; maximum score=4; higher score means worse dyspnea) | 3 months and 12 months post-diagnosis |
| Change in inflammatory cytokine biomarker - High-sensitivity CRP | Measure inflammatory cytokine biomarker high-sensitivity CRP (unit of measure: mg/L) in participants with and without exercise intolerance | At diagnosis, 3 months and 12 months post-diagnosis |
| Change in inflammatory cytokine biomarkers - IL-6 and TNF | Measure inflammatory cytokine biomarkers IL-6 and TNF-α (unit of measure: pg/mL) in participants with and without exercise intolerance | At diagnosis, 3 months and 12 months post-diagnosis |
| Change in coagulation biomarker - D-dimer | Measure coagulation biomarker D-dimer (unit of measure: ng/mL) in participants with and without exercise intolerance | At diagnosis, 3 months and 12 months post-diagnosis |
| Change in coagulation biomarker - Thrombin generation | Measure coagulation biomarker thrombin generation (unit of measure: nM·min) in participants with and without exercise intolerance | At diagnosis, 3 months and 12 months post-diagnosis |
| Change in coagulation biomarker - Fibrinolysis assay | Measure coagulation biomarker fibrinolysis assay (unit of measure: % lysis) in participants with and without exercise intolerance | At diagnosis, 3 months and 12 months post-diagnosis |
| St. Petersburg |
| Florida |
| 33701 |
| United States |
| Emory University / Children's Heathcare Atlanta | Atlanta | Georgia | 30329 | United States |
| Ann & Robert H. Lurie Children's Hospital of Chicago | Chicago | Illinois | 60611 | United States |
| Boston Children's Hospital | Boston | Massachusetts | 02115 | United States |
| Central Michigan University | Mount Pleasant | Michigan | 48859 | United States |
| Childrens Mercy Hospital | Kansas City | Missouri | 64108 | United States |
| Cincinnati Childrens Hospital | Cincinnati | Ohio | 45229 | United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | 73104 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19146 | United States |
| UT Southwestern Medical Center / Children's Medical Center | Dallas | Texas | 75235 | United States |
| Cook Childrens Medical Center | Fort Worth | Texas | 76104 | United States |
| Texas Children's Hospital | Houston | Texas | 77030 | United States |
| ID | Term |
|---|---|
| D020246 | Venous Thrombosis |
| D011655 | Pulmonary Embolism |
| ID | Term |
|---|---|
| D013927 | Thrombosis |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D004617 | Embolism |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
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