Trial record 10 of 206 for:    Dystonias

Dysport for the Treatment of OMD

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Emory University
Sponsor:
Collaborator:
Ipsen Biopharmaceuticals Inc
Information provided by (Responsible Party):
Stewart Factor, Emory University
ClinicalTrials.gov Identifier:
NCT01921270
First received: August 9, 2013
Last updated: May 9, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to study the efficacy, safety, and proper dosing of AbobotulinumtoxinA (Dysport) for use in Oromandibular Dystonia (OMD). The study hypothesis is that one of the dosing levels used will have adequate safety and efficacy.


Condition Intervention Phase
Oral Dystonia
Tardive Dystonia
Drug: AbobotulinumtoxinA
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Pilot Dose Ranging Study of Dysport® (AbobotulinumtoxinA) in the Treatment of Oromandibular Dystonia

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Global Dystonia Rating Scale [ Time Frame: 0,6 weeks ] [ Designated as safety issue: No ]
    This scale measures the severity of dystonia for a certain body part--in this study it will be "lower face" and "jaw and tongue" sections. The primary outcome will be the difference in the baseline score to the 6 week score. For the primary outcome, a BLINDED VIDEO EVALUATOR will be completing this evaluation.


Secondary Outcome Measures:
  • Global Dystonia Rating Scale [ Time Frame: 0,12 weeks ] [ Designated as safety issue: No ]
    This scale measure the severity of dystonia in a certain body part. The change from baseline to 6 weeks is the primary outcome, but from baseline to 12 weeks is a secondary outcome. For this secondary outcome measure, the scale will be completed by the BLINDED VIDEO EVALUATOR.

  • Global Dystonia Rating Scale [ Time Frame: 0,6,12 weeks ] [ Designated as safety issue: No ]
    This is a scale that measures the severity of dystonia in a certain body part. For a SECONDARY outcome, the scale will be completed by the injecting practitioner and not the blinded evaluator.

  • Analogue Pain Scale [ Time Frame: 0, 6, 12 weeks ] [ Designated as safety issue: No ]
    Measure of jaw pain by visual analogue scale (0-100)

  • SCS-PD (Sialorrhea Clinical Scale for PD) [ Time Frame: 0,6,12 weeks ] [ Designated as safety issue: No ]
    Measure of drooling

  • Estimated amount of tongue bites per day [ Time Frame: 0,6,12 weeks ] [ Designated as safety issue: Yes ]
    The patient will be asked to estimate how many times they tend to accidentally/involuntarily bite their tongue per day

  • Swallowing Disturbance Questionnaire(SDQ) [ Time Frame: 0,6,12 weeks ] [ Designated as safety issue: Yes ]
    Ease of chewing and swallowing modified to exclude questions 5, which is redundant since it regards drooling, already covered, and question 15 which is not relevant to the study as it involves prior aspiration pneumonias)

  • Fahn-Marsden Part B "Speech" Question [ Time Frame: 0,6, 12 weeks ] [ Designated as safety issue: No ]
    Question regarding ease of speech

  • Oromandibular Dystonia Quality of Life Questionnaire (OMDQ-25) [ Time Frame: 0,6,12 weeks ] [ Designated as safety issue: Yes ]
    Subjective quality of life measurement made for patients with Oromandibular Dystonia

  • Global Clinical Impression Scale (CGI) with Efficacy Index [ Time Frame: 0,6,12 weeks ] [ Designated as safety issue: Yes ]
    A measure of improvement relative to the burden of side effects

  • Unified Dystonia Rating Scale (UDRS) [ Time Frame: 0,6,12 weeks ] [ Designated as safety issue: No ]
    Rating by BLINDED video evaluators regarding severity of subject's dystonia


Estimated Enrollment: 29
Study Start Date: August 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: High Dose AbobotulinumtoxinA (Dysport)

This arm refers to Aim 1 of the study in which different dosages will be administered. For a particular muscle that is appropriate to inject, the established "high" dose will be given. It will be injected once at Week 0.

Dosage of AbobotulinumtoxinA (Dysport) per muscle:

Medial Pterygoid: 100 units Masseter: 75 units Lateral Pterygoid: 100 units Anterior digastrics: 30 units Genioglossus: 35 units

Drug: AbobotulinumtoxinA
Medication will be reconstituted at 1.5 cc of normal saline for every 300 units of abobotulinumtoxinA, then injected.
Other Name: Dysport
Active Comparator: Medium Dose AbobotulinumtoxinA (Dysport)

This arm refers to Aim 1 of the study in which different dosages will be administered. For a particular muscle that is appropriate to inject, the established "medium" dose will be given. It will be injected once at Week 0.

Dosage of AbobotulinumtoxinA (Dysport) per muscle:

Medial Pterygoid: 75 units Masseter: 50 units Lateral Pterygoid: 75 units Anterior digastrics: 20 units Genioglossus: 25 units

Drug: AbobotulinumtoxinA
Medication will be reconstituted at 1.5 cc of normal saline for every 300 units of abobotulinumtoxinA, then injected.
Other Name: Dysport
Active Comparator: Low Dose AbobotulinumtoxinA

This arm refers to Aim 1 of the study in which different dosages will be administered. For a particular muscle that is appropriate to inject, the established "low" dose will be given. It will be injected once at Week 0.

Dosage of AbobotulinumtoxinA (Dysport) per muscle:

Medial Pterygoid: 50 units Masseter: 25 units Lateral Pterygoid: 50 units Anterior digastrics: 10 units Genioglossus: 15 units

Drug: AbobotulinumtoxinA
Medication will be reconstituted at 1.5 cc of normal saline for every 300 units of abobotulinumtoxinA, then injected.
Other Name: Dysport

Detailed Description:

Study Design:

Interventional , single site, prospective study with 2 parts:

  1. Dose raging (aim 1): 3 oromandibular Dystonia (OMD) groups undergoing 3 different Dysport® dosages with a step-wise approach based on safety response. 6 weeks duration for the 3 groups.
  2. Efficacy & safety assessment of Dysport® selected dose from study part 1 (aim 2): 1 single arm with OMD subjects. 12 weeks duration.

Study Specific Aims:

Aim 1: To determine the best dose range for Dysport® for the treatment of OMD

In order to address Aim 1, patients with OMD who have been previously treated with Botox® (onabotulinumtoxinA) and responded will be recruited into this study. The muscles to be injected will be tailored to the individual's presentation and up to the injector's discretion, but if a muscle is chosen it will be given a set amount of Dysport® (abobotulinumtoxinA )(see table 2). The subject will be injected with Dysport® only, with an unblinded open-label disclosure. There will be three dose levels and three subjects will be injected in each (OMD type for each group: 2 jaw opening + 1 jaw closing).

This optimal dosage will be the safest dosage that provides adequate efficacy. This will be based on the Clinical Global Impression Scale's Efficacy Index. Subjects from Aim 1 will be offered enrollment into Aim 2.

Aim 2: To determine the efficacy and safety of Dysport® for the treatment of oromandibular dystonia

20 subjects will be included in the second part of the study and will be injected with the determined optimal dosage found at the end of the first study part. They would be injected for Aim 2 after at least 12 weeks have passed, given that the effect from the prior injection had either completely abated or at least declined significantly. The 9 subjects from Aim 1 will be offered to enter study part 2 unless they have severe adverse event (AE), ongoing AE or AE considered inappropriate for study continuation. Their previous injections with Dysport® should not confound the results of Aim 2 since both Botox® and Dysport® should both have minimal clinical effect at 12 weeks out from injection. Since the local population suffering from OMD is small, the inclusion of the Aim 1 subjects into Aim 2 would lead to a much more rapid completion of recruitment.

In both Aim 1 and Aim 2, the safety and efficacy will be recorded for all subjects that undergo injection. All subjects will be examined and videotaped at the injection visit, then at 6 and 12 weeks after injection with a standardized protocol. The primary outcome will be blinded examination scores of the videos performed after the study is complete. The evaluators will be two different movement disorders experts, not otherwise involved in the study, who will review the videotaped examinations, presented in a random order, using the Global Dystonia Rating scale (GDS). They will rate the dystonia at baseline (injection visit) and 6 weeks after injection. The change in GDS score from baseline to 6 weeks after injection is the best objective measure of efficacy and will serve as the study's primary endpoint. The investigators chose the GDS over other dystonia scales because of its ease of use, sensitivity to clinical changes because of its continuous rating system, internal consistency, and inter-rater reliability.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • a diagnosis of primary or tardive OMD
  • moderate or severe severity, defined as GDS score ≥4 in either "lower face" or "jaw and tongue" section
  • age>18 years
  • capability of attending the scheduled visits
  • only those who have been previously injected with onabotulinumtoxinA and responded to that treatment, and are at least 12 weeks post last injection
  • Women of childbearing age need to use contraception in order to be included.

Exclusion Criteria:

  • Existence of a systemic disease that could confound the evaluation
  • previous placement of Deep Brain Stimulation electrodes to treat dystonia
  • concomitant oral medications that could interfere with the action of botulinum toxin Type A (e.g., aminoglycosides)
  • on an unstable dosage of any medication prescribed to treat dystonia (e.g., benzodiazepines, baclofen or anticholinergics)
  • any known hypersensitivity to any botulinum toxin preparation and allergy to cow's milk protein
  • immunoresistance to other forms of botulinum toxin type A
  • existence of a concomitant neuromuscular disorder (e.g., Myasthenia Gravis or Lambert-Eaton syndrome, etc)
  • infection at the proposed injection sites
  • pregnant women
  • women of childbearing age NOT on contraception
  • breastfeeding women
  • inability to comply with scheduled visits
  • patients who had been previously injected with botulinum toxin type A but who did not respond
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01921270

Contacts
Contact: Michael R Silver, MD 404-778-3444 michael.r.silver@emory.edu
Contact: Elaine Sperin, LPN 404-728-4786 esperin@emory.edu

Locations
United States, Georgia
Wesley Woods Health Center; Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30329
Contact: Michael R Silver, MD    404-778-3444    michael.r.silver@emory.edu   
Contact: Elaine Sperin, LPN    404-728-4786    esperin@emory.edu   
Principal Investigator: Stewart A Factor, DO         
Sponsors and Collaborators
Emory University
Ipsen Biopharmaceuticals Inc
Investigators
Principal Investigator: Stewart A Factor, DO Emory University
  More Information

Publications:
Responsible Party: Stewart Factor, Professor, Emory University
ClinicalTrials.gov Identifier: NCT01921270     History of Changes
Other Study ID Numbers: IRB00064292
Study First Received: August 9, 2013
Last Updated: May 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
Oromandibular Dystonia
Oral Dystonia
Tardive Dystonia
botulinum toxin
abobotulinumtoxinA

Additional relevant MeSH terms:
Dystonia
Dystonic Disorders
Central Nervous System Diseases
Dyskinesias
Movement Disorders
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Botulinum Toxins, Type A
Neuromuscular Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014