Trial of OnabotulinumtoxinA for Depression in Parkinson Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03069911
Recruitment Status : Recruiting
First Posted : March 3, 2017
Last Update Posted : November 6, 2018
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Parkinson Disease Depression Biological: OnabotulinumtoxinA Biological: Control Phase 1

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  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial of OnabotulinumtoxinA for Depression in Parkinson Disease
Actual Study Start Date : November 1, 2018
Estimated Primary Completion Date : May 30, 2019
Estimated Study Completion Date : July 15, 2019

Resource links provided by the National Library of Medicine

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 Name: Normal saline

Primary Outcome Measures :
  1. Hamilton Rating Scale for Depression (HDRS) [ Time Frame: Baseline and two visits over three months (weeks 6 and 12) ]
    Improvement on a clinician-rated objective scale for depression as assessed over two weeks (6 weeks and 12 weeks after treatment)

  2. Clinical Global Impression - Improvement (CGI-I) [ Time Frame: Baseline and two visits over three months (weeks 6 and 12) ]
    Improvement on a measure of global change from screening to study discontinuation

  3. Clinical Global Impression - Severity (CGI-S) [ Time Frame: Baseline and two visits over three months (weeks 6 and 12) ]
    Improvement on measure of global illness severity from screening to study discontinuation

  4. Beck Depression Inventory II [ Time Frame: Baseline and two visits over three months (weeks 6 and 12) ]
    Improvement on a participant-rated subjective scale for depression as assessed over two visits

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 95 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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 identifier (NCT number): NCT03069911

Contact: Alexander Pantelyat, MD 410-614-1522
Contact: Kecia Garrett, B.S. 410-502-0133 ext 4, 3

United States, Maryland
Johns Hopkins University School of Medicine Recruiting
Baltimore, Maryland, United States, 21287
Contact: Alexander Pantelyat, MD    410-502-3290   
Contact: Ankur Butala, MD    410-502-0133   
Sponsors and Collaborators
Johns Hopkins University
Principal Investigator: Alexander Pantelyat, MD Johns Hopkins University

Responsible Party: Johns Hopkins University Identifier: NCT03069911     History of Changes
Other Study ID Numbers: IRB00082708
First Posted: March 3, 2017    Key Record Dates
Last Update Posted: November 6, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Deidentified group data will be shared between the two study sites (Johns Hopkins and NIH)

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 Johns Hopkins University:
Parkinson Disease

Additional relevant MeSH terms:
Depressive Disorder
Parkinson Disease
Behavioral Symptoms
Mood Disorders
Mental Disorders
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Botulinum Toxins
Botulinum Toxins, Type A
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