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

Primary Purpose

Dystonia Disorder, Parkinson Disease

Status
Recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Botulinum toxin type A
Placebo
Sponsored by
University of Calgary
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dystonia Disorder

Eligibility Criteria

30 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Movement Disorder Program, Foothills Medical Center, Alberta Health ServicesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Botulinum Toxin Type A Treatment

Placebo

Arm Description

Injections

Injections

Outcomes

Primary Outcome Measures

Change in King's Parkinson's disease pain scale score
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.
Change in Likert Visual Analogue Scale
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.

Secondary Outcome Measures

Change in Clinical Global Impression Scale
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.
Change in Movement Disorder Society Unified Parkinson Disease Rating Scale Parts 1-4 (MDS-UPDRS) ON medication
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.
Change in gait
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.
Change in Parkinson's Disease 39 item Quality of life questionnaire
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.
Number of adverse events
Adverse events assessed for safety purposes at each study visit.

Full Information

First Posted
February 10, 2020
Last Updated
May 16, 2022
Sponsor
University of Calgary
Collaborators
Allergan
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1. Study Identification

Unique Protocol Identification Number
NCT04277247
Brief Title
Botulinum Toxin Type A for Foot Dystonia-associated Pain in Parkinson's Disease
Official Title
Botulinum Toxin A (Onabotulinumtoxin A) for Foot Dystonia-associated Pain in Parkinson's Disease: A Randomized, Double-blind Placebo Control Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 12, 2021 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Calgary
Collaborators
Allergan

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dystonia Disorder, Parkinson Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
We will perform a double-blind, randomized, parallel group study evaluating the safety and efficacy of BTXA injections vs. placebo injections, targeted at painful muscles, followed by an open-label phase when all participants will receive BTXA. Subjects, caregivers, and the investigators will be blinded to assignment.
Masking
ParticipantCare ProviderInvestigator
Masking Description
Upon entry to the study, all subjects will be assigned to a subject number. Eligible subjects will be randomized to receive either BTXA injections or placebo on VISIT 1 in a double-blind manner according to a randomization schedule using computerized randomization tables as prepared by a blinded clinical nurse. All patients will receive BTXA injections on VISIT 4 in an open-label phase. The specific type of randomization used will be block randomization to ensure equal sample sizes of the BTXA and placebo groups.
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Botulinum Toxin Type A Treatment
Arm Type
Experimental
Arm Description
Injections
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Injections
Intervention Type
Drug
Intervention Name(s)
Botulinum toxin type A
Other Intervention Name(s)
BTXA
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Saline
Intervention Description
0.9% saline placebo injection
Primary Outcome Measure Information:
Title
Change in King's Parkinson's disease pain scale score
Description
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.
Time Frame
6 and 12 weeks during the parallel group phase and at 24 weeks during the open-label phase
Title
Change in Likert Visual Analogue Scale
Description
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.
Time Frame
6 and 12 weeks during the parallel group phase and at 24 weeks during the open-label phase
Secondary Outcome Measure Information:
Title
Change in Clinical Global Impression Scale
Description
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.
Time Frame
6 and 12 weeks during the parallel group phase
Title
Change in Movement Disorder Society Unified Parkinson Disease Rating Scale Parts 1-4 (MDS-UPDRS) ON medication
Description
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.
Time Frame
6 and 12 weeks during the parallel group phase
Title
Change in gait
Description
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.
Time Frame
6 and 12 weeks during the parallel group phase
Title
Change in Parkinson's Disease 39 item Quality of life questionnaire
Description
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.
Time Frame
6 and 12 weeks during the parallel group phase
Title
Number of adverse events
Description
Adverse events assessed for safety purposes at each study visit.
Time Frame
6 and 12 weeks during the parallel group phase. Adverse events will be also documented 24 weeks during the open-label phase.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: 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). 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Veronica Bruno, MD, MPH
Phone
403-220-7572
Email
veronica.bruno@ucalgary.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Beatrice Anghelescu
Phone
403-210-7542
Email
bamanghe@ucalgary.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Veronica Bruno, MD, MPH
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
Facility Information:
Facility Name
Movement Disorder Program, Foothills Medical Center, Alberta Health Services
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N4Z1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Veronica Bruno, MD, MPH
Phone
403-2220-7572
Email
veronica.bruno@ucalgary.ca
First Name & Middle Initial & Last Name & Degree
Veronica Bruno, MD, MPH

12. IPD Sharing Statement

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

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