Exercise Intolerance and Skeletal Muscle Bioenergetics in Children With Deep Venous Thrombosis

University of Texas Southwestern Medical Center5 enrolled

Overview

This is a prospective cohort study of 30 patients who are 8-21 years of age with venous thromboembolism (VTE)- either lower extremity deep venous thrombosis (DVT) or pulmonary embolism (PE).

Participants will be in three groups- those with lower extremity DVT, those with PE, or those with both lower extremity DVT and PE. Patients will have blood drawn for thrombin generation assay, thromboelastography assay, and thromboinflammatory panel in addition to standard of care labs for diagnosis of VTE and management of anticoagulation. The patients will then fill out questionnaires on quality of life and level of exercise at their first outpatient visit 4 weeks after diagnosis. At approximately 3-6 months after diagnosis, patients will undergo two days of testing for the research study. All patients will have exercise testing using bicycle ergometry to measure global aerobic fitness. They will once again fill out questionnaires about their quality of life and level of physical activity. After a 24 hour rest period, DVT patients will undergo 31P-MR Spectroscopy and non-invasive spin labeling MRI to provide data on skeletal muscle bioenergetics (phosphocreatine metabolism), and lymphatic and venous flow respectively in the affected leg compared to the unaffected leg. This will allow each patient to be his or her own control. After these research procedures, patients will continue to receive standard of care treatment for their VTE in the Bleeding and Thrombosis clinic.

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Deep Vein Thrombosis Pulmonary Embolism

Interventions

Magnetic Resonance ImagingOTHER

A. Phosphorous 31 MR Spectroscopy to evaluate skeletal muscle metabolism via measurement of depletion and recovery of phosphocreatine (PCr) B. Non-invasive arterial spin labeling MRI to evaluate lymphatic flow velocities and venous flow

Bicycle ErgometryOTHER

To measure peak VO2 as a representation of global aerobic fitness

Lab PanelOTHER

A. Inflammatory lab panel (IL-6, IL-8, TNF alpha, P-selectin, high sensitivity CRP, IL-6 receptor, TNF R1/R2) drawn at diagnosis B. Thrombin Generation Assay to measure hypercoagulability and Thromboelastography prior to initiating anticoagulation

Eligibility

Sex: ALLMin age: 8 YearsMax age: 21 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age 8- ≤ 21 years old AND * Lower extremity deep venous thrombosis OR * Lower extremity deep venous thrombosis AND pulmonary embolism OR * Pulmonary Embolism Exclusion Criteria: * Contraindications to exercise, such as post-surgical patients with cast immobility or fractures * Patients unable to follow instructions/commands at baseline due to developmental delay * Patients with congenital heart disease and abnormal pulmonary circulation/perfusion * Contraindications to undergoing magnetic resonance imaging

Locations (1)

UT Southwestern Medical Center / Children's Medical Center

Dallas, Texas, United States

Outcomes

Primary Outcomes

Phosphocreatine Depletion and Recovery

Phosphocreatine (PCr) will be measured at baseline, during performance of submaximal exercise to fatigue and then at rest in the 31 P MR Spectroscopy Scan.

Time frame: 31P MR Spectroscopy will be performed one time between 3-6 months after diagnosis.

Assessment for Venous Occlusion

Arterial spin labeling MRI will be utilized to examine venous flow in bilateral lower extremities to assess for venous occlusion.

Time frame: Arterial Spin labeling MRI will be performed one time between 3-6 months after diagnosis.

Assessment of Lymphatic flow

Arterial spin labeling MRI will be utilized to assess lymphatic flow in bilateral lower extremities to assess for adequate lymphatic drainage.

Time frame: Arterial Spin labeling MRI will be performed one time between 3-6 months after diagnosis

Inflammatory markers

A custom blood assay will be used to assess inflammation at the time of the thrombotic event. Assay will include measurements of IL-6, IL-8, TNF-alpha, CRP, IL-10, IL-6 receptor, TNF alpha receptors.

Time frame: Diagnosis to 4 weeks.

Coagulation markers

Thrombin generation assay (TGA) will be used to assess hypercoagulability, and thromboelastography will be used to assess fibrinolysis. These will be drawn at the time of the thrombotic event.

Time frame: Diagnosis to 4 weeks.

Secondary Outcomes

Exercise Intolerance

Participants will undergo Cardiopulmonary Exercise testing to assess maximal aerobic fitness.

Time frame: Pulmonary embolism patients will undergo this testing at 4-6 weeks after diagnosis. Deep venous thrombosis only patients will undergo testing at 3 months.

Data from ClinicalTrials.gov

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