Sickle Cell DiseaseSPRINTSNCT03653676
Sickle Cell Pro-Inflammatory Response to Interval Training Study
An observational study of Sickle Cell Disease, run by Ann & Robert H Lurie Children's Hospital of Chicago at 3 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 10 to 21 yearsHealthy volunteers can take part
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Exercise Test (CIIT)
- How many people
- 110 participants
- Where
- 3 sitesUnited States
- Study dates
- 2 Jan 2018to 17 Mar 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 21 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: This study will plan to enroll a total of 70 non-asthmatic subjects with SCA and 70 controls without SCA across all sites. Male or female, aged 10 years to 21 years old. Diagnosis of hemoglobin SS or S/Beta0 thalassemia confirmed by hemoglobin electrophoresis. Children and young adults on hydroxyurea are eligible but must be at steady state at time of enrollment, defined as stable dosing for at least 2 months, without anticipated changes in dose during study participation. Race and age-matched controls without SCA or sickle cell trait will be recruited among friends, relatives, siblings or individuals from similar communities to minimize confounding socio-demographic variables that may impact baseline fitness. Controls will be required to be 10 through 21 years of age.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Illinois at Chicago
Chicago, Illinois, 60608
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Sickle Cell Disease
- Being tested
- Exercise Test (CIIT)
- Keywords
- Sickle Cell Anemia, Sickle Cell Disease, Exercise, Fitness, Asthma, Inflammation
- Medical subject headings
- Anemia, Sickle Cell, Motor Activity, Asthma, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exercise Test (CIIT)Other
The CIIT exercise test will consist of 8 bouts (2 minute each) of constant workload cycling with rest periods (1 minute each) in between each bout of exercise. Subjects and controls will be randomized to either a moderate intensity or vigorous intensity, defined as 50% or 70% of the maximal workload achieved on the maximal cardiopulmonary exercise test (CPET).
| Study group | Role | What they receive |
|---|---|---|
| Subjects with SCA | Children and adolescents with SCA confirmed by hemoglobin analysis randomized to either moderate or vigorous intensity exercise test (CIIT) Receives: Other: Exercise Test (CIIT) | |
| Controls without SCA | Children and adolescents without SCA or sickle cell trait randomized to either moderate or vigorous intensity exercise test (CIIT) Receives: Other: Exercise Test (CIIT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biomarker- VCAM-1
Change in soluble vascular cell adhesion molecule VCAM-1 in ng/mL
Measured: Through study completion, approximately 2 years
Secondary outcomes (19)
Biomarker - ICAM-1
Change in intercellular adhesion molecule-1 in ng/mL
Measured: Through study completion, approximately 2 years
Biomarker - PECAM-1
Change in platelet endothelial cell adhesion molecule-1 in ng/mL
Measured: Through study completion, approximately 2 years
Biomarker - L-selectin
Change in L-selectin in ng/mL
Measured: Through study completion, approximately 2 years
Biomarker - E-selectin
Change in E-selectin in ng/mL
Measured: Through study completion, approximately 2 years
Biomarker - P-selectin
Change in P-selectin in ng/mL
Measured: Through study completion, approximately 2 years
Biomarker - IL-6
Change in interleukin-6 in pg/mL
Measured: Through study completion, approximately 2 years
Exercise spirometry
Forced expiratory volume in 1 second (FEV1 mesured in % of normal predicted value)
Measured: Through study completion, approximately 2 years
Near infrared spectroscopy (NIRS) - total oxygen saturation
Near infrared spectroscopy (NIRS) derived measurements (total oxygen saturation (StO2) in the pre-frontal cortex and vastus lateralis muscle) in %
Measured: Through study completion, approximately 2 years
Near infrared spectroscopy (NIRS) - oxygenated hemoglobin
Near infrared spectroscopy (NIRS) derived measurements (oxygenated hemoglobin in the pre-frontal cortex and vastus lateralis muscle) in %
Measured: Through study completion, approximately 2 years
Near infrared spectroscopy (NIRS) - deoxygenated hemoglobin
Near infrared spectroscopy (NIRS) derived measurements (deoxygenated hemoglobin in the pre-frontal cortex and vastus lateralis muscle) in %
Measured: Through study completion, approximately 2 years
Genomic studies
Gene and microRNA expression in mononuclear cells measured by fold change
Measured: Through study completion, approximately 2 years
Asthma risk screening - ISAAC questionnaire
International Study of Asthma and Allergies in Childhood (ISAAC) screening questionnaire for rhinitis and eczema based on yes/no responses and point system to determine severity of condition (e.g. for rhinitis, 0 to 3 points (most severe); for eczema, 0 to 4 points (most severe)).
Measured: Through study completion, approximately 2 years
Asthma risk screening - FeNO measurement
Exhaled nitric oxide (FeNO) in ppb)
Measured: Through study completion, approximately 2 years
Asthma risk screening - Urinary Leukotrienes
Urine leukotriene (LTE4) in pg/mg)
Measured: Through study completion, approximately 2 years
Eucapnic voluntary hyperventilation (EVH) spirometry
Forced expiratory volume in 1 second (FEV1 in % of normal predicted value) will be taken after EVH at 5, 10, 15, and 30 minutes to assess exercise induced bronchoconstriction in a subset of participants.
Measured: Through study completion, approximately 2 years
Adverse events
Safety outcomes including number of cardiopulmonary complications, vaso-occlusive pain or other adverse events related to exercise and EVH reported as incidence (number and %).
Measured: Through study completion, approximately 2 years
Patient reported physical functioning - fatigue
NIH PROMIS questionnaire for fatigue using appropriate raw summed and T scores with higher scores indicating worse fatigue (pediatric - raw 0 to 40, T score 30.3 to 84; parent proxy - raw 0 to 40, T score 34 to 85; adult - raw 8 to 40, T score 33.1 to 77.8)
Measured: Through study completion, approximately 2 years
Patient reported physical functioning - mobility
NIH PROMIS questionnaire for mobility using appropriate raw summed, scale or T scores with higher scores indicating better mobility (pediatric - raw 0 to 32, T-score 15.2 to 58.5; adult - raw 8 to 40, T-score 20.9 to 59.7; parent proxy - raw 0 to 32, scale 14 to 56)
Measured: Through study completion, approximately 2 years
Patient reported physical activity level
NHANES physical activity questionnaire for frequency of moderate versus vigorous physical activity in number of days in typical week (range 0 to 7 days with higher number indicating more days spent in moderate or vigorous activity) and time spent in typical day (0 to > 2 hours with higher number indicating more hours spent in moderate or vigorous activity)
Measured: Through study completion, approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2018
- Study start2 Jan 2018
- Primary completion17 Mar 2023
- Study completion17 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ann & Robert H Lurie Children's Hospital of Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- University of Illinois at Chicago, St. Jude Children's Research Hospital, Columbia University, University of California, Irvine
- Responsible party
- Principal investigator, Robert I. Liem, Ann & Robert H Lurie Children's Hospital of Chicago
- Investigators
- Robert Liem, MD, Principal investigator, Ann and Robert H. Lurie Childrens Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03653676
- Sponsor's protocol ID
- 2017-881
- Acronym
- SPRINTS
- Status last verified
- Dec 2024
- First submitted
- 2 Jan 2018
- Last updated
- 18 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cohen RT, Hankins JS, Ness KK, Hsu LL, Baynard T, Tang A, Radom-Aizik S, Guerrero K, Rodeghier M, Liem RI. Acute Exercise Challenge and Airway Dynamics in Youth With Sickle Cell Anemia: A Multicenter Study. Am J Hematol. 2026 Mar;101(3):418-426. doi: 10.1002/ajh.70170. Epub 2025 Dec 20.
PubMed 41422377
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Pro-Inflammatory Effects of Acute Exercise in Children With Sickle Cell Anemia
- ClinicalTrials.gov ID
- NCT03653676
- Acronym / sponsor ID
- SPRINTS / 2017-881
- Conditions
- Sickle Cell Disease
- Keywords
- Sickle Cell Anemia, Sickle Cell Disease, Exercise, Fitness, Asthma, Inflammation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Ann & Robert H Lurie Children's Hospital of ChicagoUniversity, hospital or other
- Collaborators
- University of Illinois at Chicago, St. Jude Children's Research Hospital, Columbia University, University of California, Irvine
- Study start
- 2 Jan 2018 (actual)
- Primary completion
- 17 Mar 2023 (actual)
- Study completion
- 17 Mar 2023 (actual)
- First posted
- 31 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Subjects with SCA | – | Other: Exercise Test (CIIT)Children and adolescents with SCA confirmed by hemoglobin analysis randomized to either moderate or vigorous intensity exercise test (CIIT) |
| Controls without SCA | – | Other: Exercise Test (CIIT)Children and adolescents without SCA or sickle cell trait randomized to either moderate or vigorous intensity exercise test (CIIT) |
Who may qualify
- Ages
- 10 to 21 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- This study will plan to enroll a total of 70 non-asthmatic subjects with SCA and 70 controls without SCA across all sites. Male or female, aged 10 years to 21 years old. Diagnosis of hemoglobin SS or S/Beta0 thalassemia confirmed by hemoglobin electrophoresis. Children and young adults on hydroxyurea are eligible but must be at steady state at time of enrollment, defined as stable dosing for at least 2 months, without anticipated changes in dose during study participation. Race and age-matched controls without SCA or sickle cell trait will be recruited among friends, relatives, siblings or individuals from similar communities to minimize confounding socio-demographic variables that may impact baseline fitness. Controls will be required to be 10 through 21 years of age.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exercise Test (CIIT)The CIIT exercise test will consist of 8 bouts (2 minute each) of constant workload cycling with rest periods (1 minute each) in between each bout of exercise. Subjects and controls will be randomized to either a moderate intensity or vigorous intensity, defined as 50% or 70% of the maximal workload achieved on the maximal cardiopulmonary exercise test (CPET). | Other | Controls without SCA, Subjects with SCA |
Primary outcome
Biomarker- VCAM-1
Time frame: Through study completion, approximately 2 years
Change in soluble vascular cell adhesion molecule VCAM-1 in ng/mL
19 secondary outcomes
Biomarker - ICAM-1
Time frame: Through study completion, approximately 2 years
Biomarker - PECAM-1
Time frame: Through study completion, approximately 2 years
Biomarker - L-selectin
Time frame: Through study completion, approximately 2 years
Biomarker - E-selectin
Time frame: Through study completion, approximately 2 years
Biomarker - P-selectin
Time frame: Through study completion, approximately 2 years
Biomarker - IL-6
Time frame: Through study completion, approximately 2 years
Exercise spirometry
Time frame: Through study completion, approximately 2 years
Near infrared spectroscopy (NIRS) - total oxygen saturation
Time frame: Through study completion, approximately 2 years
Near infrared spectroscopy (NIRS) - oxygenated hemoglobin
Time frame: Through study completion, approximately 2 years
Near infrared spectroscopy (NIRS) - deoxygenated hemoglobin
Time frame: Through study completion, approximately 2 years
Genomic studies
Time frame: Through study completion, approximately 2 years
Asthma risk screening - ISAAC questionnaire
Time frame: Through study completion, approximately 2 years
Asthma risk screening - FeNO measurement
Time frame: Through study completion, approximately 2 years
Asthma risk screening - Urinary Leukotrienes
Time frame: Through study completion, approximately 2 years
Eucapnic voluntary hyperventilation (EVH) spirometry
Time frame: Through study completion, approximately 2 years
Adverse events
Time frame: Through study completion, approximately 2 years
Patient reported physical functioning - fatigue
Time frame: Through study completion, approximately 2 years
Patient reported physical functioning - mobility
Time frame: Through study completion, approximately 2 years
Patient reported physical activity level
Time frame: Through study completion, approximately 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2024.
- Derived from this study: PubMed 41422377Cohen RT, Hankins JS, Ness KK, Hsu LL, Baynard T, Tang A, Radom-Aizik S, Guerrero K, Rodeghier M, Liem RI. Acute Exercise Challenge and Airway Dynamics in Youth With Sickle Cell Anemia: A Multicenter Study. Am J Hematol. 2026 Mar;101(3):418-426. doi: 10.1002/ajh.70170. Epub 2025 Dec 20.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Liem, MD principal investigator
Ann and Robert H. Lurie Childrens Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cell Disease, run by Ann & Robert H Lurie Children's Hospital of Chicago at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Biomarker- VCAM-1 (time frame: Through study completion, approximately 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03653676, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2024.