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

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.

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

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.