OnabotulinumtoxinA in the Management of Psychogenic Dystonia

The purpose of this research study is to evaluate if patients with psychogenic dystonia treated with onabotulinumtoxinA (BOTOX) injections will demonstrate lower severity and disability at one month and at three months than those having received placebo injections

Study Overview

• Status: Completed
• Conditions: Torticollis, Dystonia
• Intervention / Treatment: Behavioral: CBT

Detailed Description

Specific Aim 1: To investigate the effect of BoNT on PsyD severity and disability.

We will measure the changes in severity, duration, and incapacitation scores of the Rating Scale for Psychogenic Movement Disorders (RSPMD)10 in adult patients with clinically definite PsyD one month after intramuscular injections with onabotulinumtoxinA in selected muscles of the affected limb(s).

H1: PsyD patients treated with onabotulinumtoxinA injections will demonstrate lower severity and disability at one month than those having received placebo injections.

Specific Aim 2: To investigate the effect of CBT on PsyD severity and disability with and without BoNT pretreatment.

We will examine the extent to which any changes in severity and disability of PsyD, as measured by the RSPMD, after 12 weekly CBT sessions, can be influenced by pre-CBT injections with onabotulinumtoxinA.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Alberto Espay

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must meet standard criteria for clinically definite PsyD;17
• PsyD severity and disability score ≥ 10 as measured by the RSPMD (Appendix 1);10
• Dystonic posturing must have been present without remission for a period longer than 1 year.
• Between the ages of 18 and 75, inclusive

Exclusion Criteria:

• Prior treatment with any BoNT
• Presence of clinically unstable medical condition other than the condition under evaluation
• Concurrent participation in another investigational drug or device study within 30 days prior to study enrollment.
• We will also exclude subjects with medical disorders deemed at increased risk when exposed to BoNT, including myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or other neuromuscular disorders.

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
Active Comparator: CBT plus botox; Participants will be randomized to receive BoNT (onabotulinumtoxinA). Patients will undergo study assessments four weeks later. We will inject a total of 250 units of onabotulinumtoxinA, as the average optimal dose in cervical dystonia,11 using a 100:1 dilution with normal saline. The target muscles will be the ones deemed most active in the cervical region or in any of the affected limbs. If several limbs are affected, only up to two will be targeted in similar fashion, with a total dose not to exceed 400 units altogether (250 +150 units, if involvement is asymmetric or unilateral [leg and arm, respectively]; 200 + 200 units, if involvement is symmetric).	Behavioral: CBT; All participating subjects will start a 12-week CBT treatment program. These consist of weekly 1-hour CBT sessions led by a cognitive therapist. Assessments will be repeated at week 16. All PsyD subjects will undergo a 15-minute, structured diagnostic interview (Mini International Neuropsychiatric Interview (MINI)) developed to screen for axis I DSM-IV and ICD-10 psychiatric disorders. We will also use two clinician-rated instruments to assess comorbid psychopathology in PsyD patients, the 17-item Hamilton Depression Rating Scale (HAM-D), to evaluate for depressed mood, vegetative and cognitive symptoms of depression; and the 14-item Hamilton Anxiety Rating Scale (HAM-A) to evaluate psychic and somatic anxiety. These scales will be administered as part of a structured interview.
Placebo Comparator: CBT plus placebo; Participants will be randomized to receive normal saline (placebo). We will inject a total of 250 units of normal saline, as this is the average optimal dose of onabotulinumtoxinA in cervical dystonia. The target muscles will be the ones deemed most active in the cervical region or in any of the affected limbs. If several limbs are affected, only up to two will be targeted in similar fashion, with a total dose not to exceed 400 units altogether (250 +150 units, if involvement is asymmetric or unilateral [leg and arm, respectively]; 200 + 200 units, if involvement is symmetric).	Behavioral: CBT; All participating subjects will start a 12-week CBT treatment program. These consist of weekly 1-hour CBT sessions led by a cognitive therapist. Assessments will be repeated at week 16. All PsyD subjects will undergo a 15-minute, structured diagnostic interview (Mini International Neuropsychiatric Interview (MINI)) developed to screen for axis I DSM-IV and ICD-10 psychiatric disorders. We will also use two clinician-rated instruments to assess comorbid psychopathology in PsyD patients, the 17-item Hamilton Depression Rating Scale (HAM-D), to evaluate for depressed mood, vegetative and cognitive symptoms of depression; and the 14-item Hamilton Anxiety Rating Scale (HAM-A) to evaluate psychic and somatic anxiety. These scales will be administered as part of a structured interview.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rating Scale for Psychogenic Movement Disorders (RSPMD)	Primary outcome measures will be the combined severity, duration factor, and incapacitation scores (investigator-rated) of the Rating Scale for Psychogenic Movement Disorders (RSPMD, 0-12 per each limb and head [maximum for all five regions: 60]) (see Appendix 1).	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression (CGI) of change	7-point Likert scale ("very much improved," to "very much worse")	4 months
Hamilton Depression Rating Scale (HAM-D)	neuropsychiatric measures of depression.	4 months
Hamilton Anxiety Rating Scale (HAM-A)	neuropsychiatric measures of depression.	4 months

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Investigators: Principal Investigator: Alberto Espay, MD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2016
• Primary Completion (Actual): May 30, 2017
• Study Completion (Actual): June 30, 2017

Study Registration Dates

• First Submitted: October 21, 2015
• First Submitted That Met QC Criteria: November 27, 2015
• First Posted (Estimate): December 2, 2015

Study Record Updates

• Last Update Posted (Actual): November 30, 2018
• Last Update Submitted That Met QC Criteria: November 28, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Dystonia; Dystonic Disorders; Torticollis
• Other Study ID Numbers: 2015-4496

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No