Muscle-tendon Pathology and Metabolic Dysregulation in CP

Официальное название

Muscle-tendon Pathology, Metabolic Dysregulation and Chronic Inflammation in Adolescents and Young Adults With Moderate to Severe Spastic Cerebral Palsy

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое Cardiorespiratory fitness training
  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.

Первичные конечные точки

• Muscle fascicle length and muscle thickness [Срок оценки: Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)]
• Muscle fascicle pennation angle [Срок оценки: Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)]
• Passive muscle stiffness [Срок оценки: Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)]
• Isometric muscle strength [Срок оценки: Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)]
• Muscle tissue oxygenation [Срок оценки: Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)]
• Exosome size [Срок оценки: Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)]
• Exosome content [Срок оценки: Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)]
• Micro ribonucleic acid (RNA) cargo [Срок оценки: Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)]

Вторичные конечные точки (12)

• Metabolic parameters [Срок оценки: Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)]
• Pro-inflammatory cytokines [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)]
• Distance covered [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)]

Критерии участия

Критерии включения

• 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

Критерии исключения

• other forms of cerebral palsy
• orthopaedic surgery in the last 12 months
• Botulinum toxin application in the last 6 months

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

Австрия · 1 центр

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

Публикации

• 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. PMID 12198474
• 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. PMID 27188686
• 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. PMID 16978459
• 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. PMID 24708559
• 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. PMID 26853808
• 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. PMID 33679586

Идентификаторы

NCT: NCT06330922 · 10.55776/V992

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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