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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Deep Vein Thrombosis; Pulmonary Embolism
• Intervention / Treatment: Other: Magnetic Resonance Imaging; Other: Bicycle Ergometry; Other: Lab Panel; Behavioral: Questionnaires

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75235
      • UT Southwestern Medical Center / Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Venous Thromboembolism Arm; This will be a cohort of patients age 8- ≤ 21 years old with objectively diagnosed DVT and/or PE.

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; Other: Bicycle Ergometry; To measure peak VO2 as a representation of global aerobic fitness; Other: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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
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.
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.
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.

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Ayesha Zia, MD, University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2020
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: February 13, 2020
• First Submitted That Met QC Criteria: March 2, 2020
• First Posted (Actual): March 4, 2020

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Pulmonary Embolism
• Other Study ID Numbers: STU-2019-1406

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No