Exercise Program for Sickle Cell Disease
(SuCCESs Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Maryland, Baltimore
Disqualifiers: Neurological disorder, Lower extremity injury
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?The Sickle Cell Children's Exercise Study (SuCCESs) will explore the feasibility and effects of a moderate intensity strengthening, balance, speed, and agility intervention program in children with sickle cell disease.
Do I need to stop my current medications for the trial?
The trial information does not specify whether you need to stop taking your current medications.
Is the exercise program for sickle cell disease safe for humans?
The research articles reviewed do not provide specific safety data for the exercise program or the treatments mentioned under different names like SuCCESs, CASGEVY, exagamglogene autotemcel, or exa-cel. However, they do discuss the safety of other treatments for sickle cell disease, such as plerixafor, which was generally well-tolerated in patients.
12345How does the exercise program treatment for sickle cell disease differ from other treatments?
The exercise program for sickle cell disease is unique because it focuses on improving physical functioning and cardiopulmonary fitness through moderate endurance exercise, which is not a standard treatment for this condition. Unlike traditional medical treatments, this program involves regular exercise sessions, such as cycling, tailored to be safe and beneficial for individuals with sickle cell disease.
678910Eligibility Criteria
The SuCCESs trial is for children aged 6-17 who have been diagnosed with sickle cell disease. It's designed to see if a special exercise program can help them without causing harm.Inclusion Criteria
I am between 6 and 17 years old and have sickle cell disease.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Baseline Assessment
Participants perform baseline assessments including knee extension strength, locomotor efficiency, exercise tolerance, and rate of muscle activation
1 week
1 visit (in-person)
Treatment
Participants undergo a moderate intensity strengthening, balance, speed, and agility intervention program
6 weeks
6 visits (in-person), 12 home sessions
Post-intervention Assessment
Participants perform post-intervention assessments to measure outcomes such as knee extension strength, locomotor efficiency, exercise tolerance, and rate of muscle activation
1 week
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
This study tests a moderate intensity exercise program focused on strengthening, balance, speed, and agility in young patients with sickle cell disease to determine its safety and effectiveness.
1Treatment groups
Experimental Treatment
Group I: Physical Therapy ExerciseExperimental Treatment1 Intervention
There will be no control group and only one intervention delivered
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Maryland School of Medicine Dept. of Physical Therapy & Rehabilitation ScienceBaltimore, MD
University of Maryland, BaltimoreBaltimore, MD
Loading ...
Who Is Running the Clinical Trial?
University of Maryland, BaltimoreLead Sponsor
References
Dose-escalation study of ICA-17043 in patients with sickle cell disease. [2022]To determine the dose tolerance, safety, and pharmacokinetics of a single oral dose of ICA-17043 in patients with sickle cell disease.
Safety and efficacy of plerixafor dose escalation for the mobilization of CD34+ hematopoietic progenitor cells in patients with sickle cell disease: interim results. [2021]Gene therapy for sickle cell disease is limited by the yield of hematopoietic progenitor cells that can be harvested for transduction or gene editing. We therefore performed a phase I dose-escalation study of the hematopoietic progenitor cell mobilizing agent plerixafor to evaluate the efficacy and safety of standard dosing on peripheral blood CD34+ cell mobilization. Of 15 patients enrolled to date, only one was chronically transfused and ten were on hydroxyurea. Of eight patients who achieved a CD34+ cell concentration >30 cells/μL, six were on hydroxyurea. There was no clear dose response to increasing plerixafor dosage. There was a low rate of serious adverse events; two patients developed vaso-occlusive crises, at the doses of 80 μg/kg and 240 μg/kg. Hydroxyurea may have contributed to the limited CD34+ mobilization by affecting baseline peripheral blood CD34 counts, which correlated strongly with peak peripheral blood CD34 counts. Plerixafor administration did not induce significant increases in the fraction of activated neutrophils, monocytes, or platelets. However, increased neutrophils positive for activated β2 integrin and Mac-1 were associated with serious adverse events. In summary, plerixafor was well tolerated but did not achieve consistent CD34+ cell mobilization in this cohort of patients, most of whom were being actively treated with hydroxyurea and only one was chronically transfused. The study will continue with escalation of the dose of plerixafor and modification of hydroxyurea administration. Clinicaltrials.gov identifier: NCT02193191.
Successful hematopoietic stem cell mobilization and apheresis collection using plerixafor alone in sickle cell patients. [2021]Novel therapies for sickle cell disease (SCD) based on genetically engineered autologous hematopoietic stem and progenitor cells (HSPCs) are critically dependent on a safe and effective strategy for cell procurement. We sought to assess the safety and efficacy of plerixafor when used in transfused patients with SCD for HSC mobilization. Six adult patients with SCD were recruited to receive a single dose of plerixafor, tested at lower than standard (180 µg/kg) and standard (240 µg/kg) doses, followed by CD34+ cell monitoring in peripheral blood and apheresis collection. The procedures were safe and well-tolerated. Mobilization was successful, with higher peripheral CD34+ cell counts in the standard vs the low-dose group. Among our 6 donors, we improved apheresis cell collection results by using a deep collection interface and starting apheresis within 4 hours after plerixafor administration. In the subjects who received a single standard dose of plerixafor and followed the optimized collection protocol, yields of up to 24.5 × 106 CD34+ cells/kg were achieved. Interestingly, the collected CD34+ cells were enriched in immunophenotypically defined long-term HSCs and early progenitors. Thus, we demonstrate that plerixafor can be employed safely in patients with SCD to obtain sufficient HSCs for potential use in gene therapy.
Emerging disease-modifying therapies for sickle cell disease. [2020]Sickle cell disease afflicts millions of people worldwide and approximately 100,000 Americans. Complications are myriad and arise as a result of complex pathological pathways 'downstream' to a point mutation in DNA, and include red blood cell membrane damage, inflammation, chronic hemolytic anemia with episodic vaso-occlusion, ischemia and pain, and ultimately risk of cumulative organ damage with reduced lifespan of affected individuals. The National Heart, Lung, and Blood Institute's 2014 evidence-based guideline for sickle cell disease management states that additional research is needed before investigational curative therapies will be widely available to most patients with sickle cell disease. To date, sickle cell disease has been cured by hematopoietic stem cell transplantation in approximately 1,000 people, most of whom were children, and significantly ameliorated by gene therapy in a handful of subjects who have only limited follow-up thus far. During a timespan in which over 20 agents were approved for the treatment of cystic fibrosis by the Food and Drug Administration, similar approval was granted for only two drugs for sickle cell disease (hydroxyurea and L-glutamine) despite the higher prevalence of sickle cell disease. This trajectory appears to be changing, as the lack of multimodal agent therapy in sickle cell disease has spurred engagement among many in academia and industry who, in the last decade, have developed new drugs poised to prevent complications and alleviate suffering. Identified therapeutic strategies include fetal hemoglobin induction, inhibition of intracellular HbS polymerization, inhibition of oxidant stress and inflammation, and perturbation of the activation of the endothelium and other blood components (e.g. platelets, white blood cells, coagulation proteins) involved in the pathophysiology of sickle cell disease. In this article, we present a crash-course review of disease-modifying approaches (minus hematopoietic stem cell transplant and gene therapy) for patients with sickle cell disease currently, or recently, tested in clinical trials in the era following approval of hydroxyurea.
Advances in the Treatment of Sickle Cell Disease. [2019]Sickle cell disease (SCD) is a monogenic disorder that afflicts approximately 100,000 Americans and millions of people worldwide. It is characterized by hemolytic anemia, vaso-occlusive crises, relentless end-organ injury, and premature death. Currently, red blood cell transfusion and hydroxyurea are the major disease-modifying therapies available for SCD. Hematopoetic stem cell transplant is curative, but barriers to treatment are substantial and include a lack of suitable donors, immunologic transplant rejection, long-term adverse effects, prognostic uncertainty, and poor end-organ function, which is especially problematic for older patients. Gene therapy to correct the βs point mutation is under investigation as another curative modality. Deeper insights into the pathophysiology of SCD have led to the development of novel agents that target cellular adhesion, inflammation, oxidant injury, platelets and/or coagulation, vascular tone, and hemoglobin polymerization. These agents are in preclinical and clinical trials. One such agent, L-glutamine, decreases red blood cell oxidant injury and is recently US Food and Drug Administration approved to prevent acute pain episodes of SCD in patients 5 years of age or older. The purpose of this review is to describe the currently established therapies, barriers to curative therapies, and novel therapeutic agents that can target sickle cell hemoglobin polymerization and/or its downstream sequelae. A PubMed search was conducted for articles published up to May 15, 2018, using the search terms sickle cell disease, novel treatments, hematopoietic stem cell transplantation, and gene therapy. Studies cited include case series, retrospective studies, prospective clinical trials, meta-analyses, online abstracts, and original reviews.
Feasibility and safety of home exercise training in children with sickle cell anemia. [2017]Exercise guidelines do not exist for individuals with sickle cell anemia (SCA) despite the impact of disease-related complications on physical functioning. Thirteen subjects (mean 15.1 ± 2.8 years old) with SCA were prescribed three exercise sessions/week for 12 weeks on a stationary bicycle placed at home. In total, 77% of subjects completed 89% of prescribed sessions without exercise-related adverse events, thus meeting feasibility and safety criteria. Adherence to prescribed duration and target heart rate during training decreased during the second half of the study. Future trials are warranted to further evaluate training benefits associated with regular exercise in children with SCA.
Moderate-intensity endurance-exercise training in patients with sickle-cell disease without severe chronic complications (EXDRE): an open-label randomised controlled trial. [2018]Exercise could be a triggering factor for vaso-occlusive crises in patients with sickle-cell disease. We aimed to investigate whether a patient-adapted training programme of moderate endurance exercise could be safe and beneficial for patients with sickle-cell disease.
The Sickle Cell Pro-Inflammatory Response to Interval Testing Study (SPRINTS) in children and young adults with sickle cell anemia - Study design and methodological strategies. [2021]The impact of sickle cell anemia (SCA) and its complications on physical functioning and cardiopulmonary/aerobic fitness in affected individuals is significant. Although limited data support the safety of maximal cardiopulmonary exercise testing (CPET) for children and adults with SCA, the safety of submaximal moderate and high intensity, and longer duration, exercise in this population is not clear. The Sickle Cell Pro-Inflammatory Response to Interval Testing Study (SPRINTS) is a multicenter, randomized, prospective trial. SPRINTS leverages unique collaborations between investigators in pediatric hematology and exercise science to evaluate the impact of exercise intensity on the acute phase inflammatory response to exercise and changes in airway dynamics in children and young adults with SCA. Here we describe the study design and methodological strategies employed in SPRINTS, including an exercise challenge that mimics real-life patterns of childhood physical activity, characterized by multiple moderate and high intensity brief bouts of exercise interspersed with rest periods. Primary outcomes comprise pre- and post-exercise biomarkers of inflammation and endothelial dysfunction and spirometry. Secondary outcomes include assessment of physical activity and functioning, genomic studies and near-infrared spectroscopy measurements to assess tissue oxygenation status during exercise. SPRINTS aims to enroll 70 subjects with SCA and 70 matched, healthy controls. We anticipate that data from SPRINTS will address gaps in our understanding of exercise responses and safety in SCA and support the future development of evidence-based, exercise prescription guidelines in this population.
Evaluation of functional capacity for exercise in children and adolescents with sickle-cell disease through the six-minute walk test. [2022]To evaluate lung functional capacity (FC) for physical exercise in children and adolescents with sickle cell disease (SCD) through the six-minute walk test (6MWT).
An evaluation of cardiopulmonary endurance and muscular strength in adults living with sickle cell disease. [2022]There have been limited investigations into exercise in sickle cell disease (SCD). In the general population, health is reflected in general physical fitness. It is unclear if the same associations are seen in people with SCD. Here, we report a cross-sectional assessment of two important measures of physical fitness, muscle strength and cardiorespiratory endurance, in adults with SCD. A total of 29 adults with SCD (aged 24-62 years; 72% female) completed cardiopulmonary and muscular strength testing using a cycle ergometer and an isokinetic dynamometer. Adults with SCD had lower median values for cardiorespiratory endurance (the median [interquartile range, IQR] peak oxygen uptake [VO2 ] 16.1 [6.3] vs. 42.65 [11.3] ml/kg/min, p < 0.001) and knee strength (median [IQR] flexor torque 26.91[22.5] vs. 55.6 [22.7] Nm, p < 0.001) compared to controls and predicted values. Interestingly, there was a very positive association between muscular strength and peak VO2 values for adults with SCD (r = 0.53, p = 0.003) suggesting these values may be useful in determining cardiopulmonary health.