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

Pulmonary Embolism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04294849
• Other study ID #: STU-2019-1406
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 6, 2020
• Est. completion date: June 30, 2024

Study information

• Verified date: November 2023
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Other:
• Magnetic Resonance Imaging
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 Ergometry
To measure peak VO2 as a representation of global aerobic fitness
• Lab Panel
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

Behavioral:
• Questionnaires
A. Dalhousie Dyspnea Scale B. Godin Leisure Time Exercise Questionnaire C. Pediatric Venous Quality of Life Questionnaire

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center / Children's Medical Center	Dallas	Texas

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	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.	31P MR Spectroscopy will be performed one time between 3-6 months after diagnosis.
Primary	Assessment for Venous Occlusion	Arterial spin labeling MRI will be utilized to examine venous flow in bilateral lower extremities to assess for venous occlusion.	Arterial Spin labeling MRI will be performed one time between 3-6 months after diagnosis.
Primary	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.	Arterial Spin labeling MRI will be performed one time between 3-6 months after diagnosis
Primary	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.	Diagnosis to 4 weeks.
Primary	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.	Diagnosis to 4 weeks.
Secondary	Exercise Intolerance	Participants will undergo Cardiopulmonary Exercise testing to assess maximal aerobic fitness.	Pulmonary embolism patients will undergo this testing at 4-6 weeks after diagnosis. Deep venous thrombosis only patients will undergo testing at 3 months.
Secondary	Godin Leisure Time Activity Questionnaire	Patients will be asked to fill out a questionnaire to determine levels of physical activity for comparison at different time points throughout treatment.	Questionnaire to be filled out to assess activity at baseline, then one month after diagnosis, and 3-6 months after diagnosis.
Secondary	Pediatric Venous Quality of Life Questionnaire	Questionnaire to determine quality of life in various areas including school, leisure time, home, and relationships with peers.	Participants will be asked to fill this questionnaires 4 weeks after diagnosis, and 3-6 months after diagnosis.
Secondary	OSA-18 Sleep Apnea Questionnaire	Patients will be asked to complete this questionnaire to assess sleep quality and screen for obstructive sleep apnea.	Participants will be asked to fill out this questionnaire at one month post diagnosis.
Secondary	PHQ-9 Questionnaire	Participants will fill out this questionnaire to screen for depression.	Participants will be asked to fill this questionnaire one month after diagnosis.