FUVID Study: Functional Characterization of Children With Chronic Venous Thromboembolic Disease

Pulmonary Embolism Clinical Trial

Official title:

FUVID Study: A Multi-center, Prospective Study Evaluating Exercise Intolerance and Dyspnea on Exertion in Patients Following First-episode Deep Venous Thrombosis and Pulmonary Embolism

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04583878
• Other study ID #: STU-2020-0868
• Status: Recruiting
• Start date: December 22, 2020
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: University of Texas Southwestern Medical Center
• Contact: Ayesha Zia, MD, MSCS
• Phone: 214-456-7000
• Email: Ayesha.Zia[@]utsouthwestern.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a multi-center prospective cohort study of patients with first-episode deep venous thrombosis and pulmonary embolism.

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), 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 125
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 21 Years

Eligibility

Inclusion Criteria:

• Ages 8 to = 21 years
• Participant must be able to speak and understand English
• Be willing to participate and able to comply with the study protocol
• For participants with PE: Children with acute, radiologically confirmed pulmonary embolism (PE) with our without DVT
• For control group: Cohort 1: 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) Cohort 2: Children who are not prescribed physical activity restrictions and are otherwise considered to be healthy.

Exclusion Criteria:

• Congenital heart disease with abnormal pulmonary circulation or with in-situ pulmonary artery thrombosis
• Chronic kidney disease
• Chronic inflammatory or an autoimmune disorder (such as systemic lupus erythematosus, juvenile rheumatoid disorder, inflammatory bowel disease, and sickle cell disease)
• A metabolic or endocrinological disorder such as diabetes mellitus or thyroid disorder
• History of or active cancer
• Pregnant
• Musculoskeletal limitations to exercise expected to be present uptil 4 months post-diagnosis
• Weight = 300 lbs
• Contraindications to magnetic resonance imaging
• 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.
• 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:

• Prior history of DVT or PE (upper extremity, cerebral sinus venous thrombosis and abdominal thromboses encountered as a neonate are not exclusion criteria)
• Lack of anticoagulant treatment for the acute VTE due to contraindications

Related Conditions & MeSH terms

• Deep Venous Thrombosis
• Embolism
• Pulmonary Embolism
• Thrombosis
• Venous Thrombosis

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	UT Southwestern Medical Center / Children's Medical Center	Dallas	Texas
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Texas Children's Hospital	Houston	Texas
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Arkansas Children's Research Institute (ACRI)	Little Rock	Arkansas
United States	Central Michigan University	Mount Pleasant	Michigan
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Secondary	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
Secondary	Change in pulmonary/ventilatory limitations	Measured as VE/VCO2 in participants with and without exercise intolerance during cardiopulmonary testing	3 months and 12 months post-diagnosis
Secondary	Change in muscle metabolic aberrations	Measured by % phosphocreatine (PCr) depletion (? %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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in inflammatory cytokine biomarkers - IL-6 and TNF	Measure inflammatory cytokine biomarkers IL-6 and TNF-a (unit of measure: pg/mL) in participants with and without exercise intolerance	At diagnosis, 3 months and 12 months post-diagnosis
Secondary	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
Secondary	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
Secondary	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

External Links

•   FUVID Website