Trial of OnabotulinumtoxinA for Depression in Parkinson Disease

Randomized Controlled Trial of OnabotulinumtoxinA for Depression in Parkinson Disease

This study evaluates the efficacy of onabotulinumtoxinA (BOTOX®) in the treatment of depression associated with Idiopathic Parkinson Disease in adults. As a Randomized Controlled Trial, half of the participants will receive onabotulinumtoxinA injections and half will receive a placebo saline solution.

Study Overview

• Status: Terminated
• Conditions: Depression; Parkinson Disease
• Intervention / Treatment: Biological: OnabotulinumtoxinA; Biological: Control

Detailed Description

Depression is a common, but treatable, comorbid condition often seen in persons with Idiopathic Parkinson Disease (iPD). Depression in Parkinson Disease may be hard to treat as patients with iPD may be sensitive to side effect of medication. As a result, other treatments which have better side effects profiles than antidepressants may be equivalent (or better) options.

OnabotulinumtoxinA is a purified formulation of botulinum toxin serotype A which is widely utilized for neurological (and cosmetic) purposes in medicine. OnabotulinumtoxinA has preliminary studies showing it may be beneficial for the treatment of Major Depressive Disorder when given in isolated injections to facial muscles (corrugator and procerus). When given in low doses, onabotulinumtoxinA is thought to have minimal side effects.

The investigators propose that a single treatment onabotulinumtoxinA may improve symptoms of depression in persons with Parkinson Disease over three months compared to placebo. The investigators plan to use both subjective and objective evaluations of depression symptoms and regular physical exams to ensure physical (motor) symptoms of Parkinson Disease do not worsen.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent is obtained in the English language;
• They are a 18 to 95 years old;
• They meet United Kingdom Brain Bank Criteria for probable idiopathic Parkinson disease;
• They meet Diagnostic and Statistical Manual (DSM)-IV criteria for major depressive disorder (MDD) as diagnosed by the M.I.N.I. at screening;
• They are judged by the investigator to have the capacity to understand the nature of the study;
• They are willing to comply with all the requirements of the study;
• They are considered by the investigator to be likely to adhere to the protocol.

Exclusion Criteria:

• They have been treated with onabotulinumtoxinA injected into the facial muscles for any reason in the 3 months prior to screening;
• They have Bipolar Disorder, Post-Traumatic Stress Disorder, a Psychotic Disorder or any other non-unipolar depressive disorder as a principal diagnosis in the 6 months prior to screening;
• They endorse active suicidal ideation at enrollment or during any study visit, or have attempted suicide in the six months prior to screening;
• They have a history of substance abuse or dependence in the 2 months prior to screening;
• They test positive for illicit drugs on urine screen, and this has not been adequately explained to the satisfaction of the investigator
• They are considered to be at significant risk of committing homicide;
• They have an unstable medical condition;
• Women of childbearing potential who are pregnant or are considering becoming pregnant during the length of the study;
• There has been a change in their PD medication or psychotherapy treatment regimen in the 30 days preceding screening;
• They are regarded, for any reason, by the principal investigator as being an unsuitable candidate for the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; One injection of onabotulinumtoxinA (29 units for women and 40 units for men) will be injected into two facial muscles - the corrugator and procerus.	Biological: OnabotulinumtoxinA; OnabotulinumtoxinA (29 units for women; 40 units for men) diluted with 0.9% sodium chloride (saline) solution to 40 units per milliliter (mL) (0.725 mL for women, 1 mL for men); Other Names: Botox; Botulinum Toxin Type A
Placebo Comparator: Control; One injection of saline solution will be injected into two facial muscles - the corrugator and procerus.	Biological: Control; 0.9% sodium chloride solution (saline) solution injections (0.725mL for women, 1mL for men); Other Names: Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Rating Scale for Depression (HDRS)	Improvement on a clinician-rated objective scale for depression as assessed over two weeks (6 weeks and 12 weeks after treatment)	Baseline and two visits over three months (weeks 6 and 12)
Clinical Global Impression - Improvement (CGI-I)	Improvement on a measure of global change from screening to study discontinuation	Baseline and two visits over three months (weeks 6 and 12)
Clinical Global Impression - Severity (CGI-S)	Improvement on measure of global illness severity from screening to study discontinuation	Baseline and two visits over three months (weeks 6 and 12)
Beck Depression Inventory II	Improvement on a participant-rated subjective scale for depression as assessed over two visits	Baseline and two visits over three months (weeks 6 and 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Severity Score for Glabellar Frown Lines	Assessment of change in participant frowning before and after onabotulinumtoxinA injections and relationship with depressive symptoms	Baseline and two visits over three months (weeks 6 and 12)

Collaborators and Investigators

• Sponsor: Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): May 30, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: February 28, 2017
• First Submitted That Met QC Criteria: February 28, 2017
• First Posted (Actual): March 3, 2017

Study Record Updates

• Last Update Posted (Actual): August 6, 2019
• Last Update Submitted That Met QC Criteria: August 2, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Depression; Parkinson Disease; OnabotulinumtoxinA; BOTOX; Parkinsonism
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mood Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Depression; Depressive Disorder; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: IRB00082708

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Deidentified group data will be shared between the two study sites (Johns Hopkins and NIH)

Drug and device information, study documents

• 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