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Effectiveness of Botox on Reducing Rest Tremor in Parkinson's Disease

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ClinicalTrials.gov Identifier: NCT03301272
Recruitment Status : Recruiting
First Posted : October 4, 2017
Last Update Posted : January 10, 2019
Sponsor:
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

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. We 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 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 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 ARAT scores.


Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: Onabotulinumtoxin A Injection Other: Placebo Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
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.
Primary Purpose: Treatment
Official Title: Effectiveness of Onabotulinumtoxin A on Reduction of Rest Tremor in Parkinson's Disease: a Pilot Study
Actual Study Start Date : March 22, 2018
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Onabotulinumtoxin A Injection, then Placebo
Participants first receive Onabotulinumtoxin A Injection and following a 3-month washout, they receive Placebo
Drug: Onabotulinumtoxin A Injection
Reconstituted 10 units/0.1 mL. Administered intramuscular once
Other Name: Botox

Other: Placebo
0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.
Other Name: Normal saline

Experimental: Placebo, then Onabotulinumtoxin A Injection
Participants first receive placebo injection and following a 3-month washout, they receive Onabotulinumtoxin A Injection.
Drug: Onabotulinumtoxin A Injection
Reconstituted 10 units/0.1 mL. Administered intramuscular once
Other Name: Botox

Other: Placebo
0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.
Other Name: Normal saline




Primary Outcome Measures :
  1. Change in Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III tremor subscore after onabotulinumtoxinA on a limb afflicted by medically-refractory rest tremor in Parkinson's disease. [ Time Frame: Prior to injection and at 30 days after injection ]
    MDS-UPDRS is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society with high internal consistency. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III, motor examination (18 items). The subscale now has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe.


Secondary Outcome Measures :
  1. Change in the Action Research Arm Test (ARAT) score after onabotulinumtoxinA on a limb afflicted by medically-refractory rest tremor in Parkinson's disease. [ Time Frame: Prior to injection and at 30 days after injection ]

    The ARAT is an evaluated measure to assess specific changes in limb function after neurologic sequelae. It assesses a person's ability to handle objects differing in size, weight and shape and therefore can be considered to be an arm-specific measure of activity limitation. Values given are score at post-intervention minus score at baseline, score at 1-month follow-up minus score at baseline.

    The ARAT is a 19 item measure divided into 4 sub-tests (grasp, grip, pinch, and gross arm movement). Performance on each item is rated on a 4-point ordinal scale ranging from: 3: Performs test normally 2: Completes test, but takes abnormally long or has great difficulty 1: Performs test partially 0: Can perform no part of test The maximum score on the ARAT is 57 points (possible range 0 to 57)


  2. Change in tremor amplitude in centimeters (cm) and frequency in Hertz (Hz) [ Time Frame: Prior to injection and at 30 days after injection ]
    The Px1 is a novel, external measuring device which uses motion-capture technology to determine the frequency, direction, and amplitude of movement between joints within the hand. Oscillatory movement is captured using a camera system and without ever applying any direct pressure upon the limb. Output includes tremor frequency in (Hertz Hz), and distance traveled by a hand joint as compared to other joints on the hand in centimeters (cm)



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Ages Eligible for Study:   45 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03301272


Contacts
Contact: Diana Drazheva (919) 962-5336 didiana@neurology.unc.edu

Locations
United States, North Carolina
UNC Hospitals Neurology Clinic Recruiting
Chapel Hill, North Carolina, United States, 27517
Contact: Daniel Roque, MD    984-974-2266    droque@neurology.unc.edu   
Contact: Diana Drazheva    919-962-5336    didiana@neurology.unc.edu   
Principal Investigator: Daniel A Roque, MD         
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Daniel A Roque, MD University of North Carolina, Chapel Hill

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT03301272     History of Changes
Other Study ID Numbers: 15-1831
First Posted: October 4, 2017    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: January 2019

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of North Carolina, Chapel Hill:
Parkinson, Botox, Tremor

Additional relevant MeSH terms:
Parkinson Disease
Tremor
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Dyskinesias
Neurologic Manifestations
Signs and Symptoms
onabotulinumtoxinA
Botulinum Toxins, Type A
abobotulinumtoxinA
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents