Botulinum Toxin Type A for Foot Dystonia-associated Pain in Parkinson's Disease

May 16, 2022 updated by: Veronica Bruno, University of Calgary

Botulinum Toxin A (Onabotulinumtoxin A) for Foot Dystonia-associated Pain in Parkinson's Disease: A Randomized, Double-blind Placebo Control Study

To study the effects of Botulinum toxin type A (BTXA) in the treatment of foot dystonia-associated pain in Parkinson's disease

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Dystonia-associated pain, particularly in the lower limbs is the second most common type of pain in Parkinson's disease (PD). Involuntary muscle contractions that cause slow repetitive movements or abnormal postures are common. The movements may be painful and present in different ways, from just foot inversion or hallux extension to complex forms. They may affect the quality of life of patients in different ways during both ON and OFF periods. Cures for foot dystonia symptoms in PD are not yet available. Yet, improving pain symptoms can improve patients' quality of life. BTXA has been proposed as a safe and useful option for the treatment of PD patients affected by foot dystonia as it could improve symptoms locally without modifying any antiparkinsonian medications. Injected into muscles, BTXA could reduce rigidity, stiffness and improve abnormal postures that may cause foot pain. Recognizing different uses of BTXA will help to understand the symptomatic treatment for each patient in any stage of the disease. The results will help doctors to use new tools to treat foot-dystonia pain in patients with PD.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2
  • 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 Backup

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N4Z1
        • Recruiting
        • Movement Disorder Program, Foothills Medical Center, Alberta Health Services
        • Contact:

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

Ages Eligible for Study

28 years to 98 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subjects with PD according to the MDS Clinical diagnostic criteria for Parkinson's disease
  • Participants with foot dystonia not responding to antiparkinsonian agents or changes in antiparkinsonian medications schedule sufficiently as per Movement Disorders Specialist. Subjects with bilateral foot dystonia will be injected in the side where the symptoms are more severe.
  • BTXA treatment naïve subjects or not received any within the last six months (including other indications).
  • Stable PD and pain medications for at least 30 days.
  • Competence to self-report pain severity in the King's Parkinson's disease pain scale (KPPS) and a Likert Visual Analogue Scale (VAS)

Exclusion Criteria:

  • Subjects with a primary cause of pain in the lower limbs unrelated to PD foot dystonia and associated with another medical condition, e.g. severe arthritis.
  • Subjects that because of the severity or refractory pain are under an unfixed analgesic schedule.
  • Subjects who are unable to self- report pain severity in the selected scales. Patients that may require a translator or are illiterate will be included as long as they can self-report pain severity.
  • Subjects who are undergoing acute infections or other acute intercurrence.

  • Any contraindication to receiving BTXA injections:

    1. Subjects who are hypersensitive to any BTXA or any ingredient in the formulation or component of the container (Clostridium Botulinum toxin type A neurotoxin complex 900 kD, Human Serum Albumin and Sodium Chloride).
    2. The presence of infection at the proposed injection site(s).

We decided to exclude patients with high risk cardiovascular disease in the case of severe orthostatic hypotension occurring secondary to the BTXA injections (reported in less than 1% of treated cases). Systemic toxic effects of BTXA are rarely reported and most of the cases in the literature are children. In order to absolutely avoid this potential complication, we will exclude patients who report sickness/infections during the study visit

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: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Botulinum Toxin Type A Treatment
Injections
Drug: Botulinum toxin type A
A standardized dose will be injected in each muscle: 25 Units of BTXA in the extensor hallucis longus in 1 site, 50 Units of BTXA in the flexor digitorum brevis in 2 sites and 25 Units of BTXA in the tibialis posterior in 1 site.
Other Names:
  • BTXA
Placebo Comparator: Placebo
Injections
Drug: Placebo
0.9% saline placebo injection
Other Names:
  • Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in King's Parkinson's disease pain scale score
Time Frame: 6 and 12 weeks during the parallel group phase and at 24 weeks during the open-label phase
The measure foot dystonia-associated pain change perceived by the patients. The scale is composed of 14 questions exploring the frequency and severity of different pain syndromes that are frequently observed in Parkinson's disease patients, which can be summed to form an overall pain intensity score. Each item is scored by severity (0-3) multiplied by frequency (0-4), resulting in a subscore of 0 to 12, with a total possible score range from 0 to 168. Higher scores are indicative of worse outcomes.
6 and 12 weeks during the parallel group phase and at 24 weeks during the open-label phase
Change in Likert Visual Analogue Scale
Time Frame: 6 and 12 weeks during the parallel group phase and at 24 weeks during the open-label phase
The measure of foot dystonia-associated pain change perceived by the patients. The most simple Likert Visual Analogue Scale is a straight horizontal line of fixed length, usually 100 mm. The ends are defined as the extreme limits of the parameter to be measured (symptom, pain, health) orientated from the left (worst) to the right (best). There are no numerical values on this scale however, a positioning towards the left of the scale indicates a worse outcome.
6 and 12 weeks during the parallel group phase and at 24 weeks during the open-label phase

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Clinical Global Impression Scale
Time Frame: 6 and 12 weeks during the parallel group phase
Changes in scores on the Clinical Global Impression (CGI) scale. CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients).CGI scores range from 1 (very much improved) through to 7 (very much worse). Treatment response ratings should take account of both therapeutic efficacy and treatment-related adverse events and range from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects). Each component of the CGI is rated separately; the instrument does not yield a global score.
6 and 12 weeks during the parallel group phase
Change in Movement Disorder Society Unified Parkinson Disease Rating Scale Parts 1-4 (MDS-UPDRS) ON medication
Time Frame: 6 and 12 weeks during the parallel group phase
Measures changes of symptom severity, treatment response and the efficacy of treatments. Part 1 (non-motor experiences of daily living), Part 2 (motor experiences of daily living), Part 3 (motor examination) and Part 4 (motor complications). The maximum score for all the parts is 272. Higher scores are indicative of worse outcomes.
6 and 12 weeks during the parallel group phase
Change in gait
Time Frame: 6 and 12 weeks during the parallel group phase
Changes in gait will be assessed according to the sections Postural Instability/Gait Difficulty sub-score of the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS UPDRS) part 3. Higher score indicative or worse outcomes.
6 and 12 weeks during the parallel group phase
Change in Parkinson's Disease 39 item Quality of life questionnaire
Time Frame: 6 and 12 weeks during the parallel group phase
This 39 - item questionnaire assesses Parkinson's disease-specific health-related quality over the last month. It assesses how often patients experience difficulties across 8 quality of life dimensions including functioning and well being. Scores can range from 0 to 100. The higher score is indicative of worse quality of life.
6 and 12 weeks during the parallel group phase
Number of adverse events
Time Frame: 6 and 12 weeks during the parallel group phase. Adverse events will be also documented 24 weeks during the open-label phase.
Adverse events assessed for safety purposes at each study visit.
6 and 12 weeks during the parallel group phase. Adverse events will be also documented 24 weeks during the open-label phase.

Collaborators and Investigators

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

Sponsor

University of Calgary

Collaborators

Allergan

Investigators

  • Principal Investigator: Veronica Bruno, MD, MPH, University of Calgary

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 (Actual)

January 12, 2021

Primary Completion (Anticipated)

December 1, 2022

Study Completion (Anticipated)

December 1, 2022

Study Registration Dates

First Submitted

February 10, 2020

First Submitted That Met QC Criteria

February 18, 2020

First Posted (Actual)

February 20, 2020

Study Record Updates

Last Update Posted (Actual)

May 17, 2022

Last Update Submitted That Met QC Criteria

May 16, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • REB19-1645

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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