Effectiveness of Botox on Reducing Rest Tremor in Parkinson's Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease; Tremor
Intervention: Onabotulinumtoxin A Injection; Placebo
Intervention description: Reconstituted 10 units/0.1 mL. Administered intramuscular once; 0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.
Intervention MeSH terms: Botulinum Toxins, Type A; abobotulinumtoxinA
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: The study will comprise of a double blinded, crossover study where the subjects will serve as their own controls. There will be no medication changes made to Parkinson's disease medications throughout the subjects' participation in the study.
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Double-blinded study whereby the subject, the movement disorder specialist injecting neurotoxin, and the movement disorder specialist rating the patient will be unaware of the solution injected and/or planned for injection same day. To ensure that the injecting specialist is blinded to the solution, syringes will be premixed by a separate member of the research team and de-identified of any possible labels that would indicate the properties of the solution being administered to the subject.
Enrollment: 16.0
Sex: All
Minimum age: 45 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Parkinson, Botox, Tremor

Summary:

      Purpose: Rest tremor in Parkinson's disease is notoriously difficult to treat through
      pharmacological measures, currently only predictably attenuated by the invasive deep brain
      stimulation surgery. The investigators hope to find some predictable and clinically
      meaningful attenuation of tremor with targeted use of onabotulinum toxin on muscles involved
      in creating the tremor.

      Participants: 16 subjects who meet United Kingdom (UK) brain bank criteria for Parkinson's
      disease with medically refractory rest tremor of at least 3 cm amplitude.

      Procedures (methods): Subjects will be blinded to receive either sham saline injection versus
      onabotulinum toxin injections directed to muscle groups felt to be clinically involved in
      causing the oscillatory movement of the tremor. Assessment of tremor severity and functional
      improvement from baseline after injection will occur within group (i.e. each subject will
      serve as their own control).

      Hypotheses:

      1. (A) Onabotulinumtoxin A significantly attenuates the amplitude of medically-refractory
      rest tremor of the upper limb in Parkinson's patients as compared to sham injections; as
      measured by reduction in the Movement Disorders Society Unified Parkinson's Disease Rating
      Scale (MDS-UPDRS) tremor subscore.

      1. (B) Onabotulinumtoxin A significantly improves the limb function of Parkinson's patients
      with medically-refractory rest tremor of the upper limb as compared to sham injections; as
      measured by an increase in Action Research Arm Test (ARAT) scores.
    

Eligibility criteria:

        Inclusion Criteria:

          1. At least 45 years of age, and no more than 80 years of age.

          2. Meet UK Parkinson's disease brain bank diagnostic criteria

          3. Have clinical evidence of rest tremor of one or both upper extremities defined as
             involuntary, rhythmic oscillations about any joint within the upper extremities

          4. Rest tremor amplitude must be at minimum 3 cm as determined by expert opinion by a
             movement disorders specialist. Confirmation of amplitude measurement will be obtained
             from the Px1 prior to active participation in the study but will not be used for
             inclusion/exclusion in study participation.

          5. Rest tremor must be historically refractory to at least 2 categories of medications
             typically used as anti-parkinsonian agents including levodopa formulations, dopamine
             agonists, amantadine, and anticholinergics.

          6. Participants must be able to make no changes to their anti-parkinsonian medications
             for 150 days (study duration). Ability and safety to do so must also be determined by
             the participant's treating physician and confirmed in writing prior to participating.

          7. Able to provide informed consent

        Exclusion Criteria:

          1. History of having undergone botulinum toxin injections for any other condition
             previously

          2. Allergy to carbidopa or levodopa.

          3. Prescreening Montreal Cognitive Assessment (MoCA) score less than 22

          4. Prescreening muscle weakness as determined by Medical Research Council grade less than
             5/5 on direct testing in the upper limb afflicted with rest tremor.

          5. Pregnancy: documentation of non-pregnancy by urine pregnancy test will be obtained
             from all women of child-bearing potential prior to participation

          6. Infection at the proposed injection site

          7. Those with a pre-existing, concomitant neuromuscular disorder

          8. Compromised respiratory function

          9. History of having undergone deep brain stimulation surgery for any condition