FUVID Study: Functional Characterization of Children With Chronic Venous Thromboembolic Disease
Study Details
Study Description
Brief Summary
This is a multi-center prospective cohort study of patients with first-episode deep venous thrombosis and pulmonary embolism.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
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), 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Diagnostic Test: Blood draw (Visit 1)
Labs will be drawn at Visit 1, also referred to as screening (within 60 days of diagnosis) with the standard of care labs drawn.
Diagnostic Test: Blood draw (Visits 2 and 3)
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.
|
| 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. The target accrual of the positive control group is based on feasibility and availability of funds and will be limited to 25 controls. |
Diagnostic Test: Blood draw (Visits 2 and 3)
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.
|
Outcome Measures
Primary Outcome Measures
- Change in exercise capacity [3 months and 12 months post-diagnosis]
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)
- Change in dyspnea on exertion (DOE) [3 months and 12 months post-diagnosis]
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
Secondary Outcome Measures
- Change in cardiac maladaptation [3 months and 12 months post-diagnosis]
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)
- Change in pulmonary/ventilatory limitations [3 months and 12 months post-diagnosis]
Measured as VE/VCO2 in participants with and without exercise intolerance during cardiopulmonary testing
- Change in muscle metabolic aberrations [3 months and 12 months post-diagnosis]
Measured by % phosphocreatine (PCr) depletion (Δ %PCr) during exercise using 31P magnetic resonance spectroscopy on 7 Tesla in participants with and without exercise intolerance
- Change in pulmonary vascular obstruction score in participants with and without exercise intolerance (Quantitative assessment) [At diagnosis, 3 months and 12 months post-diagnosis]
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.
- Change in pulmonary vascular obstruction score in participants with and without exercise intolerance (Qualitative assessment) [At diagnosis, 3 months and 12 months post-diagnosis]
Qualitative Assessment: Measured using pulmonary perfusion maps at diagnosis, 3 and 12 months post-diagnosis. Since qualitative, there are no minimum or maximum values.
- Change in calf muscle perfusion and venous flow in participants with and without exercise intolerance and between affected and non-affected extremity [3 months and 12 months post-diagnosis]
Measured using extremity arterial spin labelling on 7 Tesla MRI
- Change in dyspnea ratings using Dalhousie Pictorial Scale [3 months and 12 months post-diagnosis]
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)
- Change in dyspnea ratings using Borg Dyspnea Scale [3 months and 12 months post-diagnosis]
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)
- Change in dyspnea ratings using Dyspnoea-12 Scale [3 months and 12 months post-diagnosis]
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)
- Change in dyspnea ratings using Modified Medical Research Council Dyspnea Scale [3 months and 12 months post-diagnosis]
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)
- Change in inflammatory cytokine biomarker - High-sensitivity CRP [At diagnosis, 3 months and 12 months post-diagnosis]
Measure inflammatory cytokine biomarker high-sensitivity CRP (unit of measure: mg/L) in participants with and without exercise intolerance
- Change in inflammatory cytokine biomarkers - IL-6 and TNF [At diagnosis, 3 months and 12 months post-diagnosis]
Measure inflammatory cytokine biomarkers IL-6 and TNF-α (unit of measure: pg/mL) in participants with and without exercise intolerance
- Change in coagulation biomarker - D-dimer [At diagnosis, 3 months and 12 months post-diagnosis]
Measure coagulation biomarker D-dimer (unit of measure: ng/mL) in participants with and without exercise intolerance
- Change in coagulation biomarker - Thrombin generation [At diagnosis, 3 months and 12 months post-diagnosis]
Measure coagulation biomarker thrombin generation (unit of measure: nM·min) in participants with and without exercise intolerance
- Change in coagulation biomarker - Fibrinolysis assay [At diagnosis, 3 months and 12 months post-diagnosis]
Measure coagulation biomarker fibrinolysis assay (unit of measure: % lysis) in participants with and without exercise intolerance
Eligibility Criteria
Criteria
Inclusion Criteria:
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Ages 8 to ≤ 21 years
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Participant must be able to speak and understand English
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Be willing to participate and able to comply with the study protocol
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For participants with PE: Children with acute, radiologically confirmed pulmonary embolism (PE) with our without DVT
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For control group: Children who are prescribed physical activity restrictions for 2 up to 12 weeks following any minor outpatient surgery or, minor injury (surgery or injury is referred to as "diagnosis" hereafter)
Exclusion Criteria:
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Congenital heart disease with abnormal pulmonary circulation or with in-situ pulmonary artery thrombosis
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Chronic kidney disease
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Chronic inflammatory or an autoimmune disorder (such as systemic lupus erythematosus, juvenile rheumatoid disorder, inflammatory bowel disease, and sickle cell disease)
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A metabolic or endocrinological disorder such as diabetes mellitus or thyroid disorder
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History of or active cancer
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Pregnant
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Musculoskeletal limitations to exercise expected to be present uptil 4 months post-diagnosis
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Weight ≥ 300 lbs
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Contraindications to magnetic resonance imaging
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Frequent severe exacerbations of asthma defined by two or more bursts of systemic glucocorticoids (more than three days each) in the previous year or at least one hospitalization, intensive care unit stay or mechanical ventilation in the previous year. Patients should also be excluded if there are daily symptoms of asthma requiring daily use of short-acting bronchodilators such as albuterol or levalbuterol administration. The use of controller medications such as daily inhaled corticosteroids for mild persistent asthma is not exclusionary.
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Has any other medical condition, which in the opinion of the investigator may potentially compromise the safety or compliance of the patient or may preclude the patient's successful completion of the clinical study
Additional exclusion criteria for participants with PE:
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Prior history of DVT or PE (upper extremity, cerebral sinus venous thrombosis and abdominal thromboses encountered as a neonate are not exclusion criteria)
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Lack of anticoagulant treatment for the acute VTE due to contraindications
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Arkansas Children's Research Institute (ACRI) | Little Rock | Arkansas | United States | 72202 |
| 2 | Nationwide Children's Hospital | Columbus | Ohio | United States | 43205 |
| 3 | UT Southwestern Medical Center / Children's Medical Center | Dallas | Texas | United States | 75235 |
| 4 | Cook Children's Medical Center | Fort Worth | Texas | United States | 76104 |
Sponsors and Collaborators
- University of Texas Southwestern Medical Center
Investigators
- Principal Investigator: Ayesha Zia, MD, MSCS, University of Texas Southwestern Medical Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- STU-2020-0868