Clinical trial NCT04277247: 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
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Dystonia Disorder
Parkinson Disease
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Allergan
First posted: 2020-02-20
Enrollment: 40
Sex: ALL
Minimum age (years): 30
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

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:

  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

Primary outcomes:
measure: Change in King's Parkinson's disease pain scale score
timeFrame: 6 and 12 weeks during the parallel group phase and at 24 weeks during the open-label phase
measure: Change in Likert Visual Analogue Scale
timeFrame: 6 and 12 weeks during the parallel group phase and at 24 weeks during the open-label phase
Secondary outcomes:
measure: Change in Clinical Global Impression Scale
timeFrame: 6 and 12 weeks during the parallel group phase
measure: Change in Movement Disorder Society Unified Parkinson Disease Rating Scale Parts 1-4 (MDS-UPDRS) ON medication
timeFrame: 6 and 12 weeks during the parallel group phase
measure: Change in gait
timeFrame: 6 and 12 weeks during the parallel group phase
measure: Change in Parkinson's Disease 39 item Quality of life questionnaire
timeFrame: 6 and 12 weeks during the parallel group phase
measure: Number of adverse events
timeFrame: 6 and 12 weeks during the parallel group phase. Adverse events will be also documented 24 weeks during the open-label phase.
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Movement Disorder Program, Foothills Medical Center, Alberta Health Services
state: Alberta
Study officials:
affiliation: University of Calgary
name: Veronica Bruno, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: