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

Phase 2

• Conditions: Dystonia Disorder; Parkinson Disease
• Interventions: Drug: Placebo; Drug: Botulinum toxin type A

• Registration Number: NCT04277247
• Lead Sponsor: University of Calgary

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.

Study Timeline

• Study First Submitted: 2020-02-10
• Study First Submitted QC: 2020-02-18
• Study First Posted: 2020-02-20
• Study Start: 2021-01-12
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-16
• Last Update Posted: 2022-05-17
• Primary Completion: 2022-12
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Injections
Botulinum Toxin Type A Treatment	Botulinum toxin type A	Injections

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change in Clinical Global Impression Scale	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.
Number of adverse events	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.
Change in gait	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.
Change in Parkinson's Disease 39 item Quality of life questionnaire	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.
Change in Movement Disorder Society Unified Parkinson Disease Rating Scale Parts 1-4 (MDS-UPDRS) ON medication	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.

Trial Locations

Locations (1)

Movement Disorder Program, Foothills Medical Center, Alberta Health Services; 🇨🇦 Calgary, Alberta, Canada