Tremor is one of the most common symptoms in Parkinson Disease (PD), affecting almost 60% of patients. There is currently no specific treatment for tremor in PD, and 30% of patients develop drug-resistant tremor, making its management more complex. Botulinum toxin (BT) is widely used in neurology, but few studies have been carried out on the effect of BT in parkinsonian tremor without consensus on its management in parkinsonian patients. In this study, the investigators therefore propose to evaluate the effect of BT injected using precision medicine in the treatment of refractory resting tremor in patients with PD, compared with placebo injection.
Parkinson's disease (PD) is the second most common neurodegenerative disease. Tremor is one of the most common symptoms, affecting almost 60% of patients. It has a considerable impact on their quality of life, causing psychosocial stress in over 25% of patients. There is currently no specific treatment for tremor in PD, and 30% of patients develop drug-resistant tremor, making its management more complex. Botulinum toxin (BT) has been approved in France in 1994 and is widely used in neurology. To date, few studies have been carried out on the effect of BT in parkinsonian tremor: most have been open-label and have mixed parkinsonian patients and patients with essential tremor. Therefore, there is no consensus on the management of tremor in patients with PD. Nevertheless, there is a real need for treatment of refractory tremor, particularly in elderly patients, patients who cannot tolerate high doses of medication or patients who are ineligible for neurostimulation. In this study, the investigators therefore propose to evaluate the effect of BT injected using precision medicine in the treatment of refractory resting tremor in parkinsonian patients, compared with placebo injection. The investigators hypothesize that BT treatment improves parkinsonian tremor in a clinically relevant way compared to placebo injection using an optimized and personalized injection technique (doses of toxin and muscles injected). The drug will be injected intramuscularly into the muscles identified as responsible for the tremor, by an investigator specialising in injections. PD patients with resistant tremor will be included and followed up in this study for one year. BT or placebo will be injected at 6 months apart in all patients thanks to the cross over study design.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
39
Both treatments, first DYSPORT 500UI for 6 months then placebo, also for 6 months, will be administered intramuscularly using the same schedule and procedures thus allowing the blind to be maintained. The two injections will be carried at 6 months apart: the drug will be injected intramuscularly, into the muscles identified as responsible for the tremor, by an investigator specialized in carrying out injections. The doses injected will depend on the severity of the tremor and the number of muscles injected, which is conditioned by the tremor phenotype.
Both treatments, first placebo for 6 months then DYSPORT 500UI, also for 6 months, will be administered intramuscularly using the same schedule and procedures thus allowing the blind to be maintained. The two injections will be carried at 6 months apart: the drug will be injected intramuscularly, into the muscles identified as responsible for the tremor, by an investigator specialized in carrying out injections. The doses injected will depend on the severity of the tremor and the number of muscles injected, which is conditioned by the tremor phenotype.
Nîmes University Hospital
Nîmes, France
Pierre Paul Riquet Hospital - Toulouse University Hospital
Toulouse, France
The effect of botulinum toxin on the resting tremor of the upper limb refractory to treatments
It will be assessed by the PGI-C (Patient Global Impression-Change) score completed by the patient six weeks after injection and compared between treatments.
Time frame: 7,5 months
The effect of botulinum toxin on the resting tremor: evolution evaluated by the investigator
It will be assessed by the CGI-C (Clinician Global Impression-Change) investigator-level change score, six weeks after injection.
Time frame: 7,5 months
The effect of botulinum toxin on the resting tremor: severity evaluated by the investigator
It will be assessed by the delta of severity scores at the CGI-S (Clinician Global Impression-Severity) investigator level between injection and six weeks post-injection.
Time frame: 7,5 months
The effect of botulinum toxin on the resting tremor: amplitude evaluated by the investigator
It will be assessed by the delta of the item score 3.17 (amplitude) at the MDS-UPDRS III investigator level between injection and six weeks post-injection.
Time frame: 7,5 months
The effect of botulinum toxin on the resting tremor: patient-assessed severity
It will be assessed by the delta of severity scores at the patient scale PGI-S (Patient Global Impression-Severity) between injection and six weeks post-injection.
Time frame: 7,5 months
The effect of botulinum toxin on the postural tremor: evolution evaluated by the investigator
It will be assessed by the change score at the CGI-C investigator scale, at six weeks post-injection.
Time frame: 7,5 months
The effect of botulinum toxin on the postural tremor: severity evaluated by the investigator
It will be assessed by the delta of severity scores at the CGI-S investigator level between injection and six weeks post-injection.
Time frame: 7,5 months
The effect of botulinum toxin on the postural tremor: amplitude evaluated by the investigator
It will be assessed by the delta of item 3.21 (amplitude) at the MDS-UPDRS III investigator level between injection and six weeks post-injection.
Time frame: 7,5 months
The effect of botulinum toxin on the postural tremor: patient-assessed change
It will be assessed by the PGI-C scale score completed by the patient six weeks after injection and compared between groups.
Time frame: 7,5 months
The effect of botulinum toxin on the postural tremor: patient-assessed severity
It will be assessed by the delta of severity scores on the PGI-S (Patient Global Impression-Severity) scale completed by the patient between the injection and six weeks post-injection.
Time frame: 7,5 months
The effect of botulinum toxin on the Parkinsonian tremor (at rest and postural): duration
It will be assessed by the proportion of time the patient has a tremor, measured using an actimeter for 7 days prior to the assessment visit.
Time frame: 12 months
The effect of botulinum toxin on the Parkinsonian tremor (at rest and postural): amplitude
It will be assessed by the mean angular amplitude measured using motion sensors placed on the hand and arm at six weeks post-injection.
Time frame: 7,5 months
The effect of botulinum toxin on the Parkinsonian tremor (at rest and postural): frequency
It will be assessed by the mean frequency in Hertz (Hz) measured using motion sensors placed on the hand and arm at six weeks post-injection.
Time frame: 7,5 months
The effect of botulinum toxin on the patient's experience: life quality
It will be assessed by the delta of the patient's quality of life score on the PDQ-39 self-administered questionnaire between injection and six weeks post-injection.
Time frame: 7,5 months
The effect of botulinum toxin on the patient's experience: daily life activities
It will be assessed by the delta of the daily life activities score by the MDS-UPDRS scale, parts one and two between injection and six weeks post-injection.
Time frame: 7,5 months
The safety of use for botulinum toxin: muscle weakness (1)
It will be assessed by the delta of the measurement in Newton of the manual dynamometer, for the treated hand, between injection and six weeks after injection.
Time frame: 7,5 months
The safety of use for botulinum toxin: muscle weakness (2)
It will be assessed by the delta of the severity scores for muscle weakness in the treated hand, on the PGI-S (Patient Global Impression Severity) scale, completed by the patient between the injection and six weeks after the injection.
Time frame: 7,5 months
The safety of use for botulinum toxin: adverse events
It will be assessed by all the adverse events collected during the study.
Time frame: 12 months
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