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| Name | Class |
|---|---|
| Medical University of Graz | OTHER |
| Karolinska Institutet | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1: healthy individuals (cross-sectional study) | Typically developed adolescents and young adults will be recruited and measured once within the cross-sectional study. | ||
| Group 2: mildly affected individuals with cerebral palsy (cross-sectional study) | Mildly affected adolescents and young adults will be recruited and measured once within the cross-sectional study. | ||
| Group 3: moderately and severely affected individuals with cerebral palsy (cross-sectional study) | The 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cardiorespiratory fitness training | Other | Cardiorespiratory fitness training will be performed two times a week for one hour in small groups (4-5 people). The training will be conducted outdoors at track and field facilities with at least two coaches. |
| Measure | Description | Time Frame |
|---|---|---|
| Muscle fascicle length and muscle thickness | cm | Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| Muscle fascicle pennation angle | degrees | Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| Passive muscle stiffness | kilopascal (kPa) | Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| Isometric muscle strength | kg | Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| Muscle tissue oxygenation | Tissue saturation index (TSI) | Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| Exosome size | nanometers (nm) | Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| Exosome content | number/ml | Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Metabolic parameters | Glucose, C-peptide, free fatty acids, cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein in mmol/l | Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| Pro-inflammatory cytokines |
| Measure | Description | Time Frame |
|---|---|---|
| Body height | cm | Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| Body weight | kg |
Inclusion Criteria:
Exclusion Criteria:
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The patient selection is based on the inclusion and exclusion criteria from the patient pool of the local clinic for Orthopaedics and Traumatology. In addition, other interested persons/families will be informed about the study via other clinics, (pediatric orthopedic) elective medical practices, rehabilitation centers and physiotherapy facilities within the city and the surrounding area.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Annika Kruse, Dr. | Contact | 00433163802329 | annika.kruse@uni-graz.at | |
| Martin Svehlik, Dr. med. | Contact | 004331638514129 | martin.svehlik@medunigraz.at |
| Name | Affiliation | Role |
|---|---|---|
| Annika Kruse, Dr. | Institute of Human Movement Science, Sport and Health, University of Graz | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Human Movement Science, Sport and Health, University of Graz | Recruiting | Graz | 8010 | Austria |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12198474 | Background | Bell KJ, Ounpuu S, DeLuca PA, Romness MJ. Natural progression of gait in children with cerebral palsy. J Pediatr Orthop. 2002 Sep-Oct;22(5):677-82. | |
| 27188686 | Background | Graham HK, Rosenbaum P, Paneth N, Dan B, Lin JP, Damiano DL, Becher JG, Gaebler-Spira D, Colver A, Reddihough DS, Crompton KE, Lieber RL. Cerebral palsy. Nat Rev Dis Primers. 2016 Jan 7;2:15082. doi: 10.1038/nrdp.2015.82. |
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Open access to research data on which the research publications are based will be provided following the Criteria for Open Research Data presented by the Austrian Science fund (FWF). If data can be shared (i.e., anonymisation can be ensured), it will be deposited under the Creative Commons (CC BY) licence.
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Research data on which future papers are based will be made available shortly after publication.
Individual participant data (IPD) will be provided under the CC BY licence.
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| ID | Term |
|---|---|
| D002547 | Cerebral Palsy |
| D009128 | Muscle Spasticity |
| ID | Term |
|---|---|
| D001925 | Brain Damage, Chronic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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Where applicable, serum and plasma
|
| Micro ribonucleic acid (RNA) cargo | expression level | Group 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 |
| Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| Resting, mean, and peak heart rate | beats/min | 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) |
| Resting blood pressure | mmHg | Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| Distance covered | m | 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) |
| Peak oxygen uptake (VO2peak), Peak ventilation (VEpeak) | l/min | 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) |
| Peak respiratory frequency | breaths/min | 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) |
| Respiratory exchange ratio | peak carbon dioxide production (VCO2peak)/VO2peak | 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) |
| VEpeak/VO2peak | ratio | 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) |
| VEpeak/VCO2peak | ratio | 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) |
| Perceived exertion | 6-20 Borg Scale | 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) |
| Well-being and quality of life | Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD™) questionnaire | Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| Total physical activity, time spent in different intensities | min | Group 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) |
| Passive range of motion (sagittal plane) of hip, knees, ankles | degrees | Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| Step count | number | Group 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) |
| Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| Body mass index (BMI) | Body height and weight will be combined to calculate the BMI in kg/m^2 | Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| Modified Ashworth Scale Score of the Plantar flexors | number | Group 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks) |
| 16978459 | Background | Narayanan UG, Fehlings D, Weir S, Knights S, Kiran S, Campbell K. Initial development and validation of the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD). Dev Med Child Neurol. 2006 Oct;48(10):804-12. doi: 10.1017/S0012162206001745. |
| 24708559 | Background | Nooijen CF, Slaman J, Stam HJ, Roebroeck ME, Berg-Emons RJ; Learn2Move Research Group. Inactive and sedentary lifestyles amongst ambulatory adolescents and young adults with cerebral palsy. J Neuroeng Rehabil. 2014 Apr 3;11:49. doi: 10.1186/1743-0003-11-49. |
| 26853808 | Background | Verschuren O, Peterson MD, Balemans AC, Hurvitz EA. Exercise and physical activity recommendations for people with cerebral palsy. Dev Med Child Neurol. 2016 Aug;58(8):798-808. doi: 10.1111/dmcn.13053. Epub 2016 Feb 7. |
| 33679586 | Background | Howard JJ, Herzog W. Skeletal Muscle in Cerebral Palsy: From Belly to Myofibril. Front Neurol. 2021 Feb 18;12:620852. doi: 10.3389/fneur.2021.620852. eCollection 2021. |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009122 | Muscle Hypertonia |
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |