Evaluation of the Effect of Botulinum Toxin on Resting Tremor of the Refractory Upper Limb in Parkinsonians, Cross-over Study, Double Blind and Placebo-controlled (TOX PARK)

September 10, 2026 updated by: University Hospital, Toulouse
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, we 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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, we 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. We 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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
39

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Nîmes, France, 30 029
        • Nîmes University Hospital
        • Contact:
        • Principal Investigator:
          • Giovanni Castelnovo, MD
      • Toulouse, France, 31 059
        • Pierre Paul Riquet Hospital - Toulouse University Hospital
        • Contact:
        • Principal Investigator:
          • Clémence Leung, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with PD defined according to UKPDSBB criteria;
  • Men and women aged between 40 and 80 years;
  • Patients with troublesome rest tremor assessed by the CGI-S scale ≥ 3 and persistent despite the initiation of ≥ two anti-parkinsonian treatments (levodopa, dopaminergic agonist, anticholinergic), which defines drug-resistant parkinsonian tremor;
  • Patients naïve to botulinum toxin treatment;
  • Patients whose antiparkinsonian treatment has been stable for at least 4 weeks prior to inclusion and for the duration of the study;
  • Person affiliated with or beneficiary of a social security scheme;
  • Free, informed, and written consent signed by the participant and the investigator (no later than the day of inclusion and before any examination required by the research).

Exclusion Criteria:

  • Patients with tremors related to a pathology other than PD;
  • Patients with atypical parkinsonian syndrome;
  • Patients treated with drugs which have the adverse effect of causing the appearance or aggravation of tremors: lithium, sodium valproate, levetiracetam, benzodiazepines, corticosteroids, thyroid hormones, ciclosporin, alcohol, tricyclic antidepressants, theophillyne, terbutaline, antipsychotics (excluding clozapine) ;
  • Patients with hypersensitivity to the active substance or to one of the excipients (human albumin, lactulose);
  • patients with atrophy of the target muscle
  • patients with a urinary tract infection at the time of treatment if the patient suffers from urinary incontinence due to neurological detrusor overactivity
  • patients with a history of swallowing or respiratory disorders;
  • patients with marked clinical or subclinical neuromuscular transmission deficits (e.g., myasthenia gravis);
  • patients with fixed contractures Pregnant or breastfeeding women;
  • Women of childbearing age without effective contraception;
  • Patients under legal guardianship, tutorship, or curatorship.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Botulinum toxin followed by placebo arm
In this cross-over study, the patient will be his or her own control. The patient will receive both treatments at 6 months apart: DYSPORT followed by the placebo (the order of injections has been randomly assigned).
Drug: Injection of Dysport then placebo
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.
Experimental: Placebo followed by botulinum toxin arm
In this cross-over study, the patient will be his or her own control. The patient will receive both treatments at 6 months apart: placebo followed by DYSPORT (the order of injections has been randomly assigned).
Drug: Injection of placebo then Dysport
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The effect of botulinum toxin on the resting tremor of the upper limb refractory to treatments
Time Frame: 7,5 months
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.
7,5 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The effect of botulinum toxin on the resting tremor: evolution evaluated by the investigator
Time Frame: 7,5 months
It will be assessed by the CGI-C (Clinician Global Impression-Change) investigator-level change score, six weeks after injection.
7,5 months
The effect of botulinum toxin on the resting tremor: severity evaluated by the investigator
Time Frame: 7,5 months
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.
7,5 months
The effect of botulinum toxin on the resting tremor: amplitude evaluated by the investigator
Time Frame: 7,5 months
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.
7,5 months
The effect of botulinum toxin on the resting tremor: patient-assessed severity
Time Frame: 7,5 months
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.
7,5 months
The effect of botulinum toxin on the postural tremor: evolution evaluated by the investigator
Time Frame: 7,5 months
It will be assessed by the change score at the CGI-C investigator scale, at six weeks post-injection.
7,5 months
The effect of botulinum toxin on the postural tremor: severity evaluated by the investigator
Time Frame: 7,5 months
It will be assessed by the delta of severity scores at the CGI-S investigator level between injection and six weeks post-injection.
7,5 months
The effect of botulinum toxin on the postural tremor: amplitude evaluated by the investigator
Time Frame: 7,5 months
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.
7,5 months
The effect of botulinum toxin on the postural tremor: patient-assessed change
Time Frame: 7,5 months
It will be assessed by the PGI-C scale score completed by the patient six weeks after injection and compared between groups.
7,5 months
The effect of botulinum toxin on the postural tremor: patient-assessed severity
Time Frame: 7,5 months
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.
7,5 months
The effect of botulinum toxin on the Parkinsonian tremor (at rest and postural): duration
Time Frame: 12 months
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.
12 months
The effect of botulinum toxin on the Parkinsonian tremor (at rest and postural): amplitude
Time Frame: 7,5 months
It will be assessed by the mean angular amplitude measured using motion sensors placed on the hand and arm at six weeks post-injection.
7,5 months
The effect of botulinum toxin on the Parkinsonian tremor (at rest and postural): frequency
Time Frame: 7,5 months
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.
7,5 months
The effect of botulinum toxin on the patient's experience: life quality
Time Frame: 7,5 months
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.
7,5 months
The effect of botulinum toxin on the patient's experience: daily life activities
Time Frame: 7,5 months
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.
7,5 months
The safety of use for botulinum toxin: muscle weakness (1)
Time Frame: 7,5 months
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.
7,5 months
The safety of use for botulinum toxin: muscle weakness (2)
Time Frame: 7,5 months
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.
7,5 months
The safety of use for botulinum toxin: adverse events
Time Frame: 12 months
It will be assessed by all the adverse events collected during the study.
12 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The factors associated with good response to botulinum toxin treatment
Time Frame: 12 months
The correct response to treatment will be determined from the scores of the PGI-S patient scale on the severity of the tremor and on the severity of the muscle weakness.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Toulouse

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Clémence Leung, MD, University Hospital, Toulouse

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 10, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 10, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 16, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 16, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 10, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RC31/25/0444
  • PHRC 24-79 (Other Grant/Funding Number: French Ministry of Health)
  • 2026-525862-23-00 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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