Low Systemic/High Local Exercise Load in Peds SCD

Sickle Cell Anemia in Children Clinical Trial

Official title:

Low Systemic/High Local Exercise Load in Pediatric Sickle Cell Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06387758
• Other study ID #: UMMC-IRB-2022-473
• Status: Recruiting
• Phase: N/A
• Start date: September 19, 2023
• Est. completion date: June 30, 2025

Study information

• Verified date: April 2024
• Source: University of Mississippi Medical Center
• Contact: Cynthia W Karlson, PhD
• Phone: 6019842723
• Email: ckarlson[@]umc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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).

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Anemia in Children

Intervention

Behavioral:
• Low systemic strength training
Low systemic strength training. Youth will complete exercise training for 45 minutes. Eight specific exercises will be performed to target all major muscle groups: calf raises, handgrip, squats, seated row, chest press, plank, low bac extension, and crunches (Table 1). Each exercise involves contractions with moderate load but with an extended duration of up to five minutes.16,17 During each exercise session, youth will have a 5-minute warm up, 5-minute cool down, and be allowed to take rest breaks as needed (minimum 30 seconds). Youth will initially progress by decreasing the number of rest periods and then increasing load. Youth will be provided a 2 lb medicine ball, resistance weight bands, Thera Putty, and a Yoga mat for home exercises. Youth will keep this home exercise equipment.
• Moderate systemic exercise
Youth assigned to the moderate systemic exercise load group will perform whole-body aerobic exercise at 40-59% of heart rate reserve (HRR) for 45 minutes.76,111 Youth will complete moderate systemic aerobic exercise by walking at a brisk pace and swinging their arms as they walk. Exercise personnel will supervise a 5-minute warm up and 5-minute cool down via videoconferencing and remain on the phone with youth at all times during the walking exercise session. Youth will exercise until the prescribed duration is achieved or until fatigue at which point they will either reduce the intensity or stop until they recover. All training intensities will be based around HRR so it is individualized (not exceeding 59% of HRR). Youth unable to meet the initial training requirements will be slowly progressed over the 8 weeks.

Locations

Country	Name	City	State
United States	University of Mississippi Medical Center	Jackson	Mississippi

Sponsors (2)

Lead Sponsor	Collaborator
University of Mississippi Medical Center	University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

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* Note: There are 112 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Demographics and medical history (parents)	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.	through study completion, an avg. of 10 weeks
Primary	Pediatric Pain Questionnaire	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.	through study completion, an avg. of 10 weeks
Primary	Functional Disability Inventory	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	through study completion, an avg. of 10 weeks
Primary	NIH PROMIS 2582	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).	through study completion, an avg. of 10 weeks
Primary	Heart Rate Variability	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.	through study completion, an avg. of 10 weeks
Primary	Heart Rate	Vital Signs measured will include heart rate (Phillips Healthcare; Netherlands).	through study completion, an avg. of 10 weeks
Primary	Blood Pressure	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.	through study completion, an avg. of 10 weeks
Primary	Bruininks-Oseretsky Test of Motor Proficiency	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.	through study completion, an avg. of 10 weeks
Primary	American Thoracic Society 6-minute walk test	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.	through study completion, an avg. of 10 weeks
Primary	Actigraphy	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	through study completion, an avg. of 10 weeks
Primary	Daily diaries	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.	through study completion, an avg. of 10 weeks
Primary	Biomarkers	Utilizing the UMMC Immunology Biomarker Core under senior mentor Dr. Marshall, we will measure inflammatory IL-6, TNF-a, 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-a 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.	pre- 2 weeks
Primary	Medical Chart Review	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.	pre- 2 weeks