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

NCT03301272 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 15-1831
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson Disease

Keywords

Parkinson, Botox, Tremor

Outcome Measures

Primary Outcomes (1)

• 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.

  Prior to onabotulinumtoxinA injection and at 30 days after injection

Secondary Outcomes (4)

• Change in the ARAT Score

  Prior to onabotulinumtoxinA injection and at 30 days after injection

• Correlation Between MDS-UPDRS Tremor Subscore and Px1 Tremor Amplitude

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

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

  Prior to onabotulinumtoxinA injection and at 30 days after injection

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

  Prior to onabotulinumtoxinA injection and at 30 days after injection

Study Arms (2)

Onabotulinumtoxin A Injection, then Placebo

EXPERIMENTAL

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

Drug: Onabotulinumtoxin A Injection; Other: Placebo

Placebo, then Onabotulinumtoxin A Injection

EXPERIMENTAL

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

Drug: Onabotulinumtoxin A Injection; Other: Placebo

Interventions

Onabotulinumtoxin A Injection DRUG

Reconstituted 10 units/0.1 mL. Administered intramuscular once

Also known as: Botox

Onabotulinumtoxin A Injection, then Placebo; Placebo, then Onabotulinumtoxin A Injection

Placebo OTHER

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

Also known as: Normal saline

Onabotulinumtoxin A Injection, then Placebo; Placebo, then Onabotulinumtoxin A Injection

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead

Study Sites (1)

UNC Hospitals Neurology Clinic

Chapel Hill, North Carolina, 27517, United States

Location

MeSH Terms

Conditions

Parkinson Disease; Tremor

Interventions

Botulinum Toxins, Type A; Saline Solution

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Daniel Roque, MD
• Organization: University of North Carolina at Chapel Hill

droque@neurology.unc.edu

919-966-8178

Study Officials

• Daniel A Roque, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 13, 2017
• First Posted: October 4, 2017
• Study Start: March 22, 2018
• Primary Completion: August 21, 2019
• Study Completion: August 21, 2019
• Last Updated: August 17, 2020
• Results First Posted: August 17, 2020

Record last verified: 2019-08

Locations

US (1)