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Muscle-tendon Pathology and Metabolic Dysregulation in CP

Recruiting
Conditions
Cerebral Palsy, Spastic
Interventions
Other: Cardiorespiratory fitness training
Registration Number
NCT06330922
Lead Sponsor
University of Graz
Brief Summary

The main aim of this project is to gain knowledge about the muscle-tendon pathology of moderately to severely affected young people with cerebral palsy and their risk for cardiometabolic diseases and chronic inflammation. Furthermore, it will be investigated whether there are associations between the existing pathophysiology as well as inactivity and muscle function, cardiometabolic risk factors and inflammation. Moreover, the potential of the target group for adaptation of its muscular, cardiorespiratory, and endocrine system will be investigated.

The study parameters will be determined in adolescents and young adults aged 14 to 30 years with moderate to severe spastic cerebral palsy and compared with those of their less severely affected and healthy peers (cross-sectional study). In addition, the more affected individuals will participate in a 12-week training intervention (longitudinal study) performed with special tricycles (i.e., Frame Runners).

To measure the study parameters, ultrasound, strength tests, near-infrared spectroscopy, blood analyses, and spiroergometry will be used. The fitness training will be performed two times a week for 12 weeks with the Frame Runners.

Detailed Description

Background: Spastic cerebral palsy (CP) is a neuro-developmental disorder in children. Although the initial brain injury is not progressive, muscle pathology, a leading sign in affected individuals, is an on-going process. Individuals with CP are less physically active compared to their typically developing (TD) peers and severely affected individuals are most sedentary. Therefore, increased muscle wasting, decreased muscle function and cardiorespiratory fitness, metabolic dysregulation, and chronic low-grade inflammation might exist in the latter group. However, information is scarce and the role of muscle-tendon pathology and physical inactivity remains to be elucidated. Finally, it is unknown whether their tissues and organs may still adapt to health-inducing stimuli.

Objectives: The main project aims are 1) to enhance our understanding of spastic muscle-tendon pathology, risk of cardiometabolic disease, and chronic inflammation likely present in young people with more severe spastic CP, and 2) to uncover the relationship of muscle-tendon alterations and physical inactivity on muscle function and metabolism as well as cardiometabolic risk factors and systemic inflammation. Moreover, the potential for adaptation of their muscular, cardiorespiratory, and endocrine system will be investigated.

Methods: A cross-sectional study will be performed to compare severely impaired adolescents and young adults with spastic CP, their mildly affected CP and TD peers. The former group will further participate in a 12-week cardiorespiratory fitness training with Frame Runners. Muscle properties will be examined using ultrasound and shear wave elastography, and muscle function and metabolism with dynamometry and near infrared spectroscopy. Blood samples will be analyzed assessing metabolic parameters, and pro-inflammatory cytokines. Cardiorespiratory fitness will be investigated using the 6-Minute Frame Running Test and gas exchange analysis. Physical activity will be evaluated with accelerometers and activity diaries. Mental well-being and quality of life will be assessed by use of the CPCHILD™ questionnaire.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
50
Inclusion Criteria
  • spastic cerebral palsy
  • mildly, moderately or severly affected (Gross Motor Function Classification System level I-IV)
  • age range 14 - 30 years
  • ability to accept and follow verbal instructions
  • strong communication skills
  • sufficient vision (visual function that enables safe movement with reference to people and obstacles)
  • less than 15 hours of experience with the Frame Runners; healthy peers in the same age range
Exclusion Criteria
  • other forms of cerebral palsy
  • orthopaedic surgery in the last 12 months
  • Botulinum toxin application in the last 6 months

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Group 3: moderately and severely affected individuals with cerebral palsy (cross-sectional study)Cardiorespiratory fitness trainingThe results of the baseline assessment (T0) of the adolescents and young adults with moderate to severe cerebral palsy will be compared with group 1 and group 2. After the baseline assessment (T0) also used for the group comparison (see description above), group 3 enters a 12-week control period following daily routines. After the 12 weeks, the individuals will be assessed (T1) and will then start with the 12-week cardiorespiratory fitness training. The final assessment (T2) will terminate study participation of group 3.
Primary Outcome Measures
NameTimeMethod
Exosome sizeGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)

nanometers (nm)

Micro ribonucleic acid (RNA) cargoGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)

expression level

Passive muscle stiffnessGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)

kilopascal (kPa)

Isometric muscle strengthGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)

kg

Muscle tissue oxygenationGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)

Tissue saturation index (TSI)

Exosome contentGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)

number/ml

Muscle fascicle pennation angleGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)

degrees

Muscle fascicle length and muscle thicknessGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)

cm

Secondary Outcome Measures
NameTimeMethod
Peak respiratory frequencyGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), measurement after 6 weeks of training (T1_6weeks, 20 weeks), post-measurement (T2, 27 weeks)

breaths/min

VEpeak/VO2peakGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), measurement after 6 weeks of training (T1_6weeks, 20 weeks), post-measurement (T2, 27 weeks)

ratio

Step countGroup 1 & 2: within 1 week between familiarisation and baseline (T0); Group 3: within 1 week after baseline (T0), within 1 week after post-measurement (T2, 28 weeks)

number

Resting, mean, and peak heart rateGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), measurement after 6 weeks of training (T1_6weeks, 20 weeks), post-measurement (T2, 27 weeks)

beats/min

VEpeak/VCO2peakGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), measurement after 6 weeks of training (T1_6weeks, 20 weeks), post-measurement (T2, 27 weeks)

ratio

Total physical activity, time spent in different intensitiesGroup 1 & 2: within 1 week between familiarisation and baseline (T0); Group 3: within 1 week after baseline (T0), within 1 week after post-measurement (T2, 28 weeks)

min

Metabolic parametersGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)

Glucose, C-peptide, free fatty acids, cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein in mmol/l

Pro-inflammatory cytokinesGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)

e.g., Interleukin 6, tumor necrosis factor alpha in pg/ml

Resting blood pressureGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)

mmHg

Distance coveredGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), measurement after 6 weeks of training (T1_6weeks, 20 weeks), post-measurement (T2, 27 weeks)

m

Peak oxygen uptake (VO2peak), Peak ventilation (VEpeak)Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), measurement after 6 weeks of training (T1_6weeks, 20 weeks), post-measurement (T2, 27 weeks)

l/min

Respiratory exchange ratioGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), measurement after 6 weeks of training (T1_6weeks, 20 weeks), post-measurement (T2, 27 weeks)

peak carbon dioxide production (VCO2peak)/VO2peak

Perceived exertionGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), measurement after 6 weeks of training (T1_6weeks, 20 weeks), post-measurement (T2, 27 weeks)

6-20 Borg Scale

Well-being and quality of lifeGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)

Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD™) questionnaire

Passive range of motion (sagittal plane) of hip, knees, anklesGroup 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)

degrees

Trial Locations

Locations (1)

Institute of Human Movement Science, Sport and Health, University of Graz

🇦🇹

Graz, Austria

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