Sickle Cell Pro-Inflammatory Response to Interval Training Study

Status:	Recruiting
Conditions:	Anemia
Therapuetic Areas:	Hematology
Healthy:	No
Age Range:	10 - 21
Updated:	9/2/2018
Start Date:	January 2, 2018
End Date:	December 2022
Contact:	Robert Liem, MD
Email:	rliem@luriechildrens.org
Phone:	312-227-4842

The Pro-Inflammatory Effects of Acute Exercise in Children With Sickle Cell Anemia

Recommendations for exercise prescription currently do not exist for individuals with sickle
cell anemia (SCA) despite the known impact that SCA-related complications has on physical
functioning and fitness. A major barrier to increasing physical activity in SCA is the
concern that the well-described inflammatory effects of exercise could precipitate or
exacerbate complications such as vaso-occlusive pain or airway bronchoconstriction (i.e.
exercise-induced asthma). Although the investigator's preliminary data suggest that
increasing physical activity may be beneficial rather than harmful in children with SCA, the
pro-inflammatory effects associated with repeated bouts of moderate to vigorous exercise
remain poorly understood in this population. The long term goal is to address the safety and
health impact of regular exercise in children with SCA. This proposal would help establish
the safety of moderate to vigorous intensity exercise in children with SCA and importantly,
will inform the design of future clinical trials focused on exercise training as a
transformative strategy to improve fitness and overall well-being in this population.

The investigator's plan to evaluate the effect of acute exercise and exercise intensity on
circulating systemic pro-inflammatory mediators and airway bronchoconstriction in SCA. The
investigators hypothesize that regular exercise at moderate to vigorous intensity is safe for
children with SCA and do not precipitate SCA-related symptoms. In this multicenter study, 70
non-asthmatic children with SCA and 70 controls without SCA will first undergo a maximal
cardiopulmonary exercise test (CPET), then be randomized to an exercise challenge by
controlled intensity interval training (CIIT) at either moderate or vigorous intensity (8
exercise bouts at 50% or 70% peak workload, respectively). The Investigator's Aims are to: 1)
Determine the influence of exercise intensity on the acute inflammatory response to exercise,
defined by an increase in soluble vascular cell adhesion molecule (VCAM) and other adhesion
molecules, and 2) Define the effect of moderate to vigorous exercise on forced expiratory
volume in 1 second (FEV1) and acute bronchoconstriction in children with SCA. The
investigators will also explore exercise- induced changes in gene and microRNA expression in
peripheral blood mononuclear cells, tissue oxygenation during exercise by near infrared
spectroscopy as well as the role of hyperventilation in bronchoconstriction using eucapnic
voluntary hyperventilation testing in a subset of participants.

Inclusion Criteria:

- Provide signed and dated informed consent form

- Willing to comply with all study procedures and be available for the duration of the
study

- Male or female, aged 10 years to 21 years old

- Diagnosis of hemoglobin SS or S/Beta0 thalassemia confirmed by hemoglobin
electrophoresis

Exclusion Criteria:

- Inability to perform CPET due to physical limitation (e.g. severe hip osteonecrosis or
stroke)

- Enrollment on chronic transfusion program

- History of exercise-induced arrhythmia or syncope

- Diagnosis of asthma, defined as physician diagnosis or use of daily asthma medications

- Known exercise-induced bronchoconstriction, defined as physician diagnosis by exercise
challenge test

- History of any cardiac diagnosis precluding exercise testing, unless cleared by a
cardiologist

- Anything that would place the individual at increased risk or preclude the
individual's full compliance with or completion of the study

We found this trial at

sites

Columbia University Medical Center

630 W 168th St
New York, New York

212-305-2862