Low Systemic/High Local Exercise Load in Peds SCD
- Conditions
- Sickle Cell Anemia in Children
- Interventions
- Behavioral: Low systemic strength trainingBehavioral: Moderate systemic exercise
- Registration Number
- NCT06387758
- Lead Sponsor
- University of Mississippi Medical Center
- Brief Summary
This research study wants to learn about what kind of exercise is best for kids with sickle cell disease. Participating children will have a small amount of blood drawn one time at the beginning of the study. Children will then complete some questionnaires that measure pain, physical function, and emotions (depression, anxiety) and complete some tests that measure physical fitness at the beginning and end of the study. Children will be randomized to either a home-based telehealth (1) walking or (2) strengthening exercise program that lasts for 8-weeks, 3-x week, for 45 minutes each session. Children's participation will last up to 10 weeks.
- Detailed Description
Overview: The current pilot study is a randomized behavioral exercise intervention.
Procedures:
Study Phase I: Families (n=60) will complete a baseline research visit. Youth will then be randomized to one of the exercise groups and complete one instructional exercise session, in person, at the UMMC Center for Integrative Health (CIH). After the instructional exercise session youth will complete a 3-day home ambulatory monitoring protocol. Study Phase II: Youth will then complete an 8-week Telehealth home exercise protocol. Youth will complete a 3-day ambulatory monitoring protocol during weeks 4 and 8. Youth will return to the UMMC CIH within one week of completing the exercise protocol to repeat questionnaires and clinical assessment. Parents will also repeat questionnaires.
Study Phase I:
Baseline Research Visit: Once enrolled, the RA will obtain parent contact information and contact information for two other relations. Youth and their parent will complete questionnaires using REDCap electronic data collection on Apple iPads (10 minutes). Questionnaires will include items on demographics, pain, physical functioning, and negative emotions (due to depression and negative affect being among the most robust predictors of pain in youth with SCD11,63,112,113). Blood draw: A blood sample will be collected (10 minutes) for the purpose of measuring baseline inflammatory markers. Every effort will be made to collect blood during scheduled clinical blood draws and using topical lidocaine cream. Clinical and Physical fitness assessment: Next, an Actigraph GT9X-BT device will be placed on youth's wrist to monitor HRV for the duration of the baseline research visit. Youth will then complete clinical and physical fitness assessments (30 minutes; detailed below).
Exercise Intervention: Randomization. Sixty numbers will be randomly assigned to either the low systemic strength training or the moderate systemic exercise groups in a 2:1 manner using the Microsoft Excel 2013 RANDBETWEEN1,2 function. Randomization order will be password protected and unlocked just prior to the instructional exercise session. However, of note, if families indicate that they do not have a safe environment to complete the moderate systemic exercise intervention (i.e., do not have a safe place to walk outside), then the youth participant will be assigned to the low systemic strength training group. The next eligible participant will be assigned to the moderate systemic exercise group to fulfill that randomization. Instructional Exercise Session. Youth will perform one 45-minute exercise session in-person at the UMMC CIH center. Prior to beginning exercise, exercise personnel will educate youth and parents regarding safe exercise (e.g., staying hydrated, moderate exercise levels) and potential adverse events75 (e.g., fatigue, muscle soreness; see Protections against risks, Exercise Sessions for more detail). At 5 minutes before exercise; 10, 20, 30, and 40 minutes during exercise, and 5 minutes after exercise pain intensity (primary outcome) and HRV (secondary outcome) will be obtained. 3-day Ambulatory Monitoring. Following the instructional exercise session, youth will partake in 3 consecutive days of actigraphy ambulatory monitoring and complete three days of pain diary. An actigraph is worn like a watch on the wrist of your non-dominant hand and measures physical activity, sleep, and heart-rate through light and movement and heartrate variability through a heart rate monitor. Daily diary pain intensity and actigraphy-derived HRV at 24-hours will be collected and contribute toward Aim 1: Hypotheses 1a and 1b. To reduce participant burden, wrist-worn Actigraphy devices will be returned via standard mail in a padded envelope.10
Study Phase II:
8-Week Telehealth Exercise Protocol. Using a within- and between-subject design, youth will serve as their own control (pre-post) and will complete 8-weeks (3 times per week; 45-minute sessions) of either (1) low systemic strength training or (2) moderate systemic exercise training. After the instructional exercise session, all exercise sessions will be completed at the home and supervised by study exercise personnel via Telehealth. A parent must also be present in the home during each exercise session. If a parent is not present, the exercise session will be rescheduled. Exercise personnel will record exercise adverse events at each session. All adverse events will be immediately reported to the medical director and PI.
3-day Ambulatory Monitoring. During week 4 and week 8 of the Telehealth exercise protocol, youth will partake in 3 consecutive days of daily diary and actigraphy ambulatory monitoring. Wrist-worn actigraphy devices will be returned via standard mail in a padded envelope and/or at the follow-up visit.
Follow-Up Visit. Families will return to the UMMC CIH within 1 week of completing the 8-week Telehealth exercise protocol. Youth will repeat questionnaires on pain (primary outcome, Aim 2) and assessment of HRV and physical fitness (secondary outcomes, Aim 2). Parents will also repeat questionnaires.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
- youth 12 to 17 years old
- diagnosed with SCD genotype SS, SC, beta-plus thalassemia, or beta-zero thalassemia
- has daily access to an Internet enabled device (e.g., smart phone, IPad) A parent (≥21 years old) will also be recruited for each youth participant.
- non-English speaking due to lack of available written translation services for informed consent and questionnaires
- cognitive impairment (e.g., moderate to profound intellectual disability) that precludes study completion
- medical condition (e.g., hypertension, bone fracture) that precludes completing exercise safely (determined by study medical director Dr. McNaull).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Low systemic strength training Low systemic strength training 8-week (3 times per week; 45-minute sessions) home-based telehealth strengthening exercise program Moderate systemic exercise Moderate systemic exercise 8-week (3 times per week; 45-minute sessions) home-based telehealth walking protocol
- Primary Outcome Measures
Name Time Method Pediatric Pain Questionnaire through study completion, an avg. of 10 weeks The Pediatric Pain Questionnaire (PPQ, youth and parent version) is well-validated and consists of two 100 mm visual analogue scale items that measure present pain intensity and worst pain in the past week. One question of pain frequency will be added (0 = not at all to 6 = daily pain). The present pain intensity item will measure pain intensity during exercise sessions.
NIH PROMIS 2582 through study completion, an avg. of 10 weeks The NIH PROMIS 2582 (youth and parent-proxy) includes 25-items on physical function mobility, anxiety, depression, fatigue, peer relations, pain interference, and pain intensity. Items are scored on a 5-point Likert scale and converted to standard T-scores; except pain intensity (10-point numeric rating scale).
Blood Pressure through study completion, an avg. of 10 weeks Vital Signs measured will include blood pressure (BP). Systolic and diastolic blood pressure will be measured following a 5-minute rest period, three times (1 minute apart) in the non-dominant arm using automated oscillometric measurement and an appropriate-sized cuff.
Bruininks-Oseretsky Test of Motor Proficiency through study completion, an avg. of 10 weeks Physical fitness will be assessed using the well-validated Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition (4-21 years) to measure upper-limb and bilateral coordination, balance, running speed and agility, and strength.86,87 Aerobic endurance will be measured using American Thoracic Society 6-minute walk test guidelines. Dr. Daniels will train exercise personnel and the study RA in clinical assessment to proficiency and review 30% of data for research fidelity.
Biomarkers pre- 2 weeks Utilizing the UMMC Immunology Biomarker Core under senior mentor Dr. Marshall, we will measure inflammatory IL-6, TNF-α, and CRP biomarker18-21 levels. 10 mL whole blood samples will be collected in heparinized tubes.96-98 Plasma samples will be rapidly obtained by centrifugation and will be stored at -80◦C in a research freezer until batch analyzed. Inflammatory marker IL-6 and TNF-α concentrations will be analyzed using Luminex® assay kits. We will examine CRP and using antibody-sandwich ELISA (Assaypro LLC, St. Charles, MO). Standard laboratory and assay measurement limits, normal and cut-off age values will be used to define absolute and high values.
Demographics and medical history (parents) through study completion, an avg. of 10 weeks Parent name, address, email, social media contact information, child age, gender, diagnosis, prescribed medication dose and frequency, grade in school, parent marital status, parent education, and family income.
American Thoracic Society 6-minute walk test through study completion, an avg. of 10 weeks Aerobic endurance will be measured using American Thoracic Society 6-minute walk test guidelines. Dr. Daniels will train exercise personnel and the study RA in clinical assessment to proficiency and review 30% of data for research fidelity.
Heart Rate Variability through study completion, an avg. of 10 weeks HRV for both Phase I and II will be recorded using the Actigraph GT9X-BT device capable of collecting R-R intervals, and in accordance with established guidelines.22 Time Domain measures will include the standard deviation of normal RR intervals (SDNN, reflects sympathetic activity), and the square root of the mean squared differences between normal adjacent R-R intervals (RMSSD, reflects parasympathetic activity). Spectral analysis of HRV will be derived via a 1024-point linear fast Fourier transformation using a Hamming window. The resultant power density spectrum will be analyzed for total power (0.00-0.40 Hz), LF (0.04-0.15 Hz), and HF (0.15-0.40 Hz). LF and HF will be further normalized (LFNU and HFNU) to quantify sympathovagal balance.
Actigraphy through study completion, an avg. of 10 weeks Objective recordings of daily HRV will be assessed with an Actigraph GT9X-BT device and computed using the ActiLife 6 software package. The watch-like device is worn on the non-dominant wrist.92 Wrist actigraphy has been validated in both healthy children and children with chronic pain.92-95
Medical Chart Review pre- 2 weeks The following variables will be extracted from youth's electronic health record: date of birth, diagnoses, prescribed medications, complications, blood laboratory results over the past year, height and weight at last clinic visits, and number of emergency room visits and hospitalizations for pain during past three years. Complications and pain-related visits/hospitalizations will determine SCD disease severity. A potential concern in this study is the broad age range of 12-17 year olds, with children's changing immune system and differences in pubertal Tanner stage potentially impacting their physiological response to exercise. Thus, age and estimated pubertal Tanner stage will be examined as possible covariates. Pubertal status according to Tanner Stage criteria will be estimated by the pediatric hematologist/nurse practitioner at a regular office visit. All practitioners have appropriate training in pediatric examination.
Functional Disability Inventory through study completion, an avg. of 10 weeks The Functional Disability Inventory (FDI, youth and parent version)79 is a 15-item well-validated scale assessing difficulty in physical and psychosocial functioning due to physical health (0 = no trouble to 4 = impossible).80,81
Heart Rate through study completion, an avg. of 10 weeks Vital Signs measured will include heart rate (Phillips Healthcare; Netherlands).
Daily diaries through study completion, an avg. of 10 weeks Diary items are derived from the above questionnaires, created in REDCap, take less than 3 minutes to answer, and will be completed once in the evening at a specified time. A diary link will be texted or emailed to the participant's smartphone or computer. Diary items will include: pain duration (pain start and stop time), pain intensity (100 mm visual analogue scale), daily mood (e.g., worried, sad), pain medications, and functional disability. All diary information will be immediately encrypted in REDCap.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States