The Muscle in Children With Cerebral Palsy - Longitudinal Exploration of Microscopic Muscle Structure.

NCT05497609 | Recruiting

• 1 other identifier: BTX muskel CP
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Cerebral palsy (CP) is a motor impairment due to a brain malformation or a brain lesion before the age of two. Spasticity, hypertonus in flexor muscles, dyscoordination and an impaired sensorimotor control are cardinal symptoms. The brain lesion is non-progressive, but the flexor muscles of the limbs will during adolescence become relatively shorter and shorter (contracted), forcing the joints into a progressively flexed position. This will worsen the positions of already paretic and malfunctioning arms and legs. Due to bending forces across the joints, bony malformations will occur, worsening the function even further. Since about 25 years a combination treatment with intramuscular botulinum toxin injections, braces and training has had a tremendous and increasing popularity, although lasting long-term clinical advantage is not yet proven. Muscle morphology of the biceps brachii and the gastrocnemius muscles:

• The hypothesis is that care as usual, i.e. training and splinting sessions with botulinum toxin as adjuvant treatment, will reduce (normalize) the expression of the fast fatigable myosin heavy chain MyHC IIx and increase the expression of developmental myosin, as a possible sign of growth. As the biceps in the arm is used irregularly and voluntarily, and the gastrocnemius is activated during automated gait, the adaptations of those muscles will be different. Methods: Baseline muscle biopsies: Percutaneous biopsies are taken just before the first intramuscular botulinum toxin injection is given. The doses and the intervals for the botulinum toxin treatment will follow clinical routines. Biopsies 4-6 months, 12 months and 24 months after the first botulinum toxin injection: The exact same procedure as above will be performed, but the biopsies will be taken 2 cm distant, medial or lateral, from previous biopsy sites
• Significance:. More knowledge is warranted regarding the actual molecular process in the muscle leading to a contracture, and its relation to the constant communication with the injured central nervous system. This study will give answers that could result in new, early prophylactic treatment of joint movement restrictions and motor impairment in children with CP.

Conditions

Cerebral Palsy; Muscle Contraction; Muscle Spasticity

Keywords

Cerebral Palsy; Upper Limb; Lower Limb; Muscle Biopsy; Botulinum Toxin Type A

Outcome Measures

Primary Outcomes (5)

• Muscle fiber area

  um2, square micrometers, measured on specimens

  Biopsies are collected and stored in -80° freezer and then analyzed. Analyses will take place up to 20271215

• Muscle fiber types based on myosin heavy chain isoforms

  Percentage of all fibers

  Biopsies are collected and stored in -80° freezer and then analyzed. Analyses will take place up to 20271215

• Extracellular matrix, area

  um2, square micrometers, measured on specimens

  Biopsies are collected and stored in -80° freezer and then analyzed. Analyses will take place up to 20271215

• Capillaries per fiber area

  number of capillaries/um2

  Biopsies are collected and stored in -80° freezer and then analyzed. Analyses will take place up to 20271215

• Mitochondria: NADH staining, morphology

  Scoring 1, 2, 3

  Biopsies are collected and stored in -80° freezer and then analyzed. Analyses will take place up to 20271215

Secondary Outcomes (1)

• Clinical assessment, contracture

  At 0 months, 6 months, 12 months and 24 months

Interventions

no intervention. Care as ususal OTHER

No intervention

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Children with cerebral palsy and aquired brain injury who, as a part of care as usual, gets botulinum toxin injections in muscles. Children are recruited consecutively.

You may qualify if:

• Cerebral Palsy, Aquired Brain Injury

You may not qualify if:

• Progressive neural disease

Sponsors & Collaborators

• Eva Ponten: lead

Study Sites (1)

Karolinska University Hospital

Stockholm, 17176, Sweden

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Percutaneous muscle biopsies

MeSH Terms

Conditions

Cerebral Palsy; Muscle Spasticity

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Eva M Pontén, MD PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eva M Pontén, MD PhD

CONTACT

+46706303052; eva.ponten@ki.se

Alexandra Palmcrantz

CONTACT

alexandra.palmcrantz@ki.se

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD PhD Ass Prof

Study Record Dates

• First Submitted: July 27, 2022
• First Posted: August 11, 2022
• Study Start: January 15, 2006
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): December 15, 2027
• Last Updated: August 11, 2022

Record last verified: 2022-07

Locations

SE (1)