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

Primary Purpose

Parkinson Disease

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Onabotulinumtoxin A Injection

Placebo

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring Parkinson, Botox, Tremor

Eligibility Criteria

45 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

At least 45 years of age, and no more than 80 years of age.
Meet UK Parkinson's disease brain bank diagnostic criteria
Have clinical evidence of rest tremor of one or both upper extremities defined as involuntary, rhythmic oscillations about any joint within the upper extremities
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.
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.
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.
Able to provide informed consent

Exclusion Criteria:

History of having undergone botulinum toxin injections for any other condition previously
Allergy to carbidopa or levodopa.
Prescreening Montreal Cognitive Assessment (MoCA) score less than 22
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.
Pregnancy: documentation of non-pregnancy by urine pregnancy test will be obtained from all women of child-bearing potential prior to participation
Infection at the proposed injection site
Those with a pre-existing, concomitant neuromuscular disorder
Compromised respiratory function
History of having undergone deep brain stimulation surgery for any condition

Sites / Locations

UNC Hospitals Neurology Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Onabotulinumtoxin A Injection, then Placebo

Placebo, then Onabotulinumtoxin A Injection

Arm Description

Participants first receive Onabotulinumtoxin A Injection and following a 3-month washout, they receive Placebo

Participants first receive placebo injection and following a 3-month washout, they receive Onabotulinumtoxin A Injection.

Outcomes

Primary Outcome Measures

Change in the MDS-UPDRS Tremor Subscore

The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a clinimetric assessment of subjective and objective symptoms and signs of Parkinson's disease created by the Movement Disorder Society. MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used in this study is Part III's tremor subscore (3.17). The subscale has a 0-4 rating, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Higher MDS-UPDRS scores reflect worse tremor/motor function. Larger differences will infer greater effect size for the intervention. Score drops over time imply improvement in tremor/motor function.

Secondary Outcome Measures

Change in the ARAT Score

The Action Research Arm Test (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. 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: 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). Higher ARAT scores reflect greater preservation of function in tested arm. Larger differences will infer greater effect sizes for the intervention. Score drops over time imply worsening limb function.

Correlation Between MDS-UPDRS Tremor Subscore and Px1 Tremor Amplitude

MDS-UPDRS retains the four-scale structure with a reorganization of the various subscales. The subscale used is Part III's tremor subscore 3.17. The subscale has a 0-4 rating: (0=no tremor, 1=<1cm, 2=1-3 cm, 3=3-10 cm, 4=>10cm). Higher scores reflect worse tremor amplitude. Larger differences infer greater effect size. The Px1 is a novel, external measuring device using motion-capture technology to determine the frequency, direction and amplitude of movement between hand joints. Movement is captured without ever applying direct pressure on the limb. Output includes tremor frequency in Hz and distance traveled by a hand joint as compared to other joints on the hand in cm. The largest tremor amplitude measured by Px1 was acquired 3x/visit, values averaged then compared with the amplitude range corresponding to MDS-UPDRS tremor subscore. This process was repeated for all subjects for Visits 1-4 comparing all values using Spearman correlation coefficient.

Change in Tremor Amplitude in Centimeters (cm) as Measured by Px1

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)

Change in Tremor Frequency in Hertz (Hz) as Measured by Px1

Full Information

NCT ID

NCT03301272

First Posted

September 13, 2017

Last Updated

July 28, 2020

Sponsor

University of North Carolina, Chapel Hill

1. Study Identification

Unique Protocol Identification Number

NCT03301272

Brief Title

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

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

March 22, 2018 (Actual)

Primary Completion Date

August 21, 2019 (Actual)

Study Completion Date

August 21, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of North Carolina, Chapel Hill

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson Disease

Keywords

Parkinson, Botox, Tremor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

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

ParticipantCare ProviderInvestigator

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.

Allocation

Randomized

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Onabotulinumtoxin A Injection, then Placebo

Arm Type

Experimental

Arm Description

Participants first receive Onabotulinumtoxin A Injection and following a 3-month washout, they receive Placebo

Arm Title

Placebo, then Onabotulinumtoxin A Injection

Arm Type

Experimental

Arm Description

Participants first receive placebo injection and following a 3-month washout, they receive Onabotulinumtoxin A Injection.

Intervention Type

Drug

Intervention Name(s)

Onabotulinumtoxin A Injection

Other Intervention Name(s)

Botox

Intervention Description

Reconstituted 10 units/0.1 mL. Administered intramuscular once

Intervention Type

Other

Intervention Name(s)

Placebo

Other Intervention Name(s)

Normal saline

Intervention Description

0.9% normal saline solution, mimicking Botox injection paradigm. Administered intramuscular once.

Primary Outcome Measure Information:

Title

Change in the MDS-UPDRS Tremor Subscore

Description

Time Frame

Prior to onabotulinumtoxinA injection and at 30 days after injection

Secondary Outcome Measure Information:

Title

Change in the ARAT Score

Description

Time Frame

Prior to onabotulinumtoxinA injection and at 30 days after injection

Title

Correlation Between MDS-UPDRS Tremor Subscore and Px1 Tremor Amplitude

Description

Time Frame

At Visit 1, prior to 1st injection through Visit 4, 30 days after last injection

Title

Change in Tremor Amplitude in Centimeters (cm) as Measured by Px1

Description

Time Frame

Prior to onabotulinumtoxinA injection and at 30 days after injection

Title

Change in Tremor Frequency in Hertz (Hz) as Measured by Px1

Description

Time Frame

Prior to onabotulinumtoxinA injection and at 30 days after injection

10. Eligibility

Sex

All

Minimum Age & Unit of Time

45 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: At least 45 years of age, and no more than 80 years of age. Meet UK Parkinson's disease brain bank diagnostic criteria Have clinical evidence of rest tremor of one or both upper extremities defined as involuntary, rhythmic oscillations about any joint within the upper extremities 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. 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. 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. Able to provide informed consent Exclusion Criteria: History of having undergone botulinum toxin injections for any other condition previously Allergy to carbidopa or levodopa. Prescreening Montreal Cognitive Assessment (MoCA) score less than 22 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. Pregnancy: documentation of non-pregnancy by urine pregnancy test will be obtained from all women of child-bearing potential prior to participation Infection at the proposed injection site Those with a pre-existing, concomitant neuromuscular disorder Compromised respiratory function History of having undergone deep brain stimulation surgery for any condition

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Daniel A Roque, MD

Organizational Affiliation

University of North Carolina, Chapel Hill

Official's Role

Principal Investigator

Facility Information:

Facility Name

UNC Hospitals Neurology Clinic

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27517

Country

United States

12. IPD Sharing Statement

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

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