Muscle-tendon Pathology and Metabolic Dysregulation in CP

Cerebral Palsy, Spastic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06330922
• Other study ID #: 10.55776/V992
• Status: Recruiting
• Start date: March 8, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: March 2024
• Source: University of Graz
• Contact: Annika Kruse, Dr.
• Phone: 00433163802329
• Email: annika.kruse[@]uni-graz.at
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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 25 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.

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-tendon 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 information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 14 Years to 25 Years

Eligibility

Inclusion Criteria:

• spastic cerebral palsy

• mildly, moderately or severly affected (Gross Motor Function Classification System level I-IV)

• age range 14 - 25 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

Related Conditions & MeSH terms

• Cerebral Palsy
• Cerebral Palsy, Spastic
• Muscle Spasticity

Intervention

Other:
• 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.

Locations

Country	Name	City	State
Austria	Institute of Human Movement Science, Sport and Health, University of Graz	Graz

Sponsors (3)

Lead Sponsor	Collaborator
University of Graz	Karolinska Institutet, Medical University of Graz

Country where clinical trial is conducted

Austria, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Body height	cm	Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)
Other	Body weight	kg	Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)
Other	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)
Other	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)
Primary	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)
Primary	Muscle fascicle pennation angle	degrees	Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)
Primary	Passive muscle stiffness	kilopascal (kPa)	Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)
Primary	Isometric muscle strength	kg	Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)
Primary	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)
Primary	Exosome size	nanometers (nm)	Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)
Primary	Exosome content	number/ml	Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)
Primary	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)
Secondary	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)
Secondary	Pro-inflammatory cytokines	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)
Secondary	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)
Secondary	Resting blood pressure	mmHg	Group 1 & 2: baseline (T0); Group 3: baseline (T0), pre-measurement (T1, 13 weeks), post-measurement (T2, 27 weeks)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)