Effect of Botulinum Toxin on Muscles of Children With Cerebral Palsy

NCT ID: NCT02853240

Last Updated: 2020-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-24
• Study Completion Date: 2020-01-10

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Children with spastic CP receiving toxin injections

Children with spastic cerebral palsy receiving toxin injections

Group Type: EXPERIMENTAL

Muscle biopsy

Intervention Type: 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.

Interventions

Muscle biopsy

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.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

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

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hôpital Femme Mère Enfant

Bron, , France

Countries

France

Other Identifiers

2016-001610-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

69HCL15_0540

Identifier Type: -

Identifier Source: org_study_id