Effect of Botulinum Toxin on Muscles of Children With Cerebral Palsy

NCT02853240 | Completed

• 2 other identifiers: 69HCL15_05402016-001610-24
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Cerebral palsy (CP) is a group of non-progressive motor dysfunction but often changing, secondary to injury or brain abnormalities that occur in early stages of development. In children with CP, the brain injury lead to a delayed motor development in the first weeks, associated with muscular spasticity. Drug treatments include oral treatments (baclofen and tizanidine) and injectable treatments like Botox (intramuscular injection) and neurolysis with alcohol or phenol (local injection into the nerve). Regarding botulinum toxin, there is no study questioning its effectiveness. However, no publication on the pathophysiology of human muscle of the CP child after toxin injection was found. The action of the toxin on the neuromuscular junction (NMJ) and muscle structure is unknown in children with CP. The primary objective of this study is to describe structural abnormalities of the CP child's muscle following multiple toxin injections in terms of NMJ fragmentation and axonal sprouting. Secondary objectives: To evaluate the relationship between:

• The severity of the motor impairment and muscle structural abnormalities.
• The clinical measure of spasticity and muscle structural abnormalities.
• To compare the structure spastic muscles with toxin injections and spastic muscle without toxin injections For muscles with multiple toxin injections, assessing the relationship between :
• The number of toxin injections and muscle structural abnormalities.
• The date of the first injection and muscle structural abnormalities.
• The total dose of injected toxin in the muscle and its structural abnormalities.
• The nature of the product injected in the muscle and its structural abnormalities. This innovative study will improve the knowledge on the effects of long-term botulinum toxin injections on the muscle (and therefore its safety in usual care), on the spastic muscle NMJ of CP children, on the pathophysiology of the CP child's muscle. All the visits all acts will be performed according to usual patient follow-up. Only a biopsy will be performed in addition, taken from an injected muscle during a planned operation. A biopsy may also be performed on a muscle without toxin injection if the act is made possible by the planned surgery. No biopsy will be made on a muscle that would not require surgery.

Conditions

Cerebral Palsy

Keywords

Cerebral palsy; children; muscle spasticity; botulinum toxin injection

Outcome Measures

Primary Outcomes (2)

• Presence of neuromuscular junctions fragmentation (both qualitative and quantitative).

  The biopsy is performed at the same time of a scheduled general anesthesia surgery (multisite surgery). The biopsy is 2 to 3 mm x 10 mm. It is a simple and quick gesture, usually practiced by surgeon

  6 months maximum (time of surgery)

• Presence of axonal sprouting (qualitative).

  6 months maximum (time of surgery)

Secondary Outcomes (7)

• Proportion of muscles with neuromuscular junctions fragmentation (both qualitative and quantitative) and/or axonal sprouting (qualitative) according to patient's GMFCS grade (1 to 5).

  6 months maximum (time of surgery)

• Proportion of muscles with neuromuscular junctions fragmentation (both qualitative and quantitative) and/or axonal sprouting (qualitative) according to Ashworth score.

  6 months maximum (time of surgery)

• Proportion of muscles with neuromuscular junctions fragmentation (both qualitative and quantitative) and/or axonal sprouting (qualitative) according to Tardieu score.

  6 months maximum (time of surgery)

• Proportion of muscles with neuromuscular junctions fragmentation (both qualitative and quantitative) and/or axonal sprouting (qualitative) according to the number of toxin injections in the muscle.

  6 months maximum (time of surgery)

• Proportion of muscles with neuromuscular junctions fragmentation (both qualitative and quantitative) and/or axonal sprouting (qualitative) according to the delay (in months) since the first toxin injection in the muscle

  6 months maximum (time of surgery)

Study Arms (1)

Children with spastic CP receiving toxin injections

EXPERIMENTAL

Children with spastic cerebral palsy receiving toxin injections

Procedure: Muscle biopsy

Interventions

Muscle biopsy PROCEDURE

A biopsy (specifically done for the study) of a muscle that has already been injected with botulinum toxin before inclusion of the patient in the study will be performed, taken during a planned surgery (for tendon transfer or muscle lengthening). A biopsy of a muscle that has never been injected with botulinum toxin may be performed during surgery. No biopsy will be made on a member that would not require surgery. Thus sampling will be conducted on a muscle requiring a surgery: 2 to 3 millimeters will be taken on 10 mm muscle before transfer or lengthening.

Children with spastic CP receiving toxin injections

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age Children \> 7 years and \<18 years
• With spastic cerebral palsy (all grades of the combined GMFCS
• Having an orthopedic surgical indication already planned on the lower limbs
• Receiving toxin injections
• With social security coverage
• Whose parents / holders of parental authority have signed the consent form

You may not qualify if:

• Patients with an evolutive CP
• Children with a baclofen pump
• Children who underwent neurotomy or functional dorsal rhizotomy, or alcohol or phenol injections

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hôpital Femme Mère Enfant

Bron, 69500, France

Location

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 Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2016
• First Posted: August 2, 2016
• Study Start: October 24, 2016
• Primary Completion: January 10, 2020
• Study Completion: January 10, 2020
• Last Updated: January 18, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)