Clinical trial NCT03301272: Effectiveness of Botox on Reducing Rest Tremor in Parkinson's Disease
Official title: Effectiveness of Onabotulinumtoxin A on Reduction of Rest Tremor in Parkinson's Disease: a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson Disease
Keywords: Parkinson, Botox, Tremor
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
First posted: 2017-10-04
Enrollment: 16
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

Brief 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.

Detailed description: For purposes of properly identifying muscles intended for injection, a portable electromyography will be attached to an appropriate gauge electromyography-guided botulinum toxin needle, which in turn will be used to hear/see motor evoked potentials (MEPs). Subjects will be asked to activate the muscle while needle is inserted to ensure proper placement of the needle in the desired muscle prior to injection of study solution.

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

Primary outcomes:
measure: Change in the MDS-UPDRS Tremor Subscore
timeFrame: Prior to onabotulinumtoxinA injection and at 30 days after injection
Secondary outcomes:
measure: Change in the ARAT Score
timeFrame: Prior to onabotulinumtoxinA injection and at 30 days after injection
measure: Correlation Between MDS-UPDRS Tremor Subscore and Px1 Tremor Amplitude
timeFrame: At Visit 1, prior to 1st injection through Visit 4, 30 days after last injection
measure: Change in Tremor Amplitude in Centimeters (cm) as Measured by Px1
timeFrame: Prior to onabotulinumtoxinA injection and at 30 days after injection
measure: Change in Tremor Frequency in Hertz (Hz) as Measured by Px1
timeFrame: Prior to onabotulinumtoxinA injection and at 30 days after injection
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: UNC Hospitals Neurology Clinic
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Daniel A Roque, MD
role: PRINCIPAL_INVESTIGATOR
References: