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Pretarsal Versus Preseptal Botulinum Toxin for Patients With Eyelid Spasm

Primary Purpose

Blepharospasm, Hemifacial Spasm, Botulinum Toxins, Type A

Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Botulinum Toxin Type A 100Unit/Vial (Product)
Saline Solution for Injection
Sponsored by
The University of Hong Kong
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Blepharospasm focused on measuring Eyelid, Dystonia, Botulinum injection, Oculoplastics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients over 18 years-of-age
  • Clinical diagnosis eyelid dystonia, consisting of either blepharospasm or hemifacial spasm
  • Patient wish to have treatment with botulinum toxin type A (BtA).

Exclusion Criteria:

  • Patients unable to express their symptoms or history to the extent that they are not able to complete the study questionnaires, such as those suffering from dementia.
  • Existence of potential contraindications to BtA treatment:

    • Pregnancy
    • Breastfeeding
    • Prior allergic reaction
    • Active infection or inflammation in the treatment area
    • Neuromuscular and peripheral neuropathic disease
    • Concomitant aminoglycoside therapy
  • Patients with poor or unstable general health with activities of daily living severely affected by non-dystonia confounding factors, such as hospitalized or bed bound patients.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Active Comparator

    Arm Label

    Preseptal-pretarsal

    Pretarsal-preseptal

    Arm Description

    The Preseptal-pretarsal group will receive injections of Botulinum Toxin Type A 100Unit/Vial (Product) in the preseptal site (Injection pattern A) and Saline Solution for Injection (placebo control) in the pretarsal site for 2 cycles at 3 months apart. Both groups will crossover and receive the alternative intervention. Hence in the second half of the trial, the Preseptal-pretarsal group will be injected with BtA in Pattern B and Pretarsal-preseptal group will receive Pattern A.

    The Pretarsal-preseptal group will initially receive injections Botulinum Toxin Type A 100Unit/Vial (Product) in the reverse with the intervention at the pretarsal site (Injection pattern B) for 2 cycles at 3 months apart. Groups 1 and 2 will crossover and receive the alternative intervention. Both groups will crossover and receive the alternative intervention. Hence in the second half of the trial, the Preseptal-pretarsal group will be injected with BtA in Pattern B and Pretarsal-preseptal group will receive Pattern A.

    Outcomes

    Primary Outcome Measures

    Jankovic Rating Scale (JRS)
    The severity of the patient's spasm employing the widely used JRS scale. The JRS is scored between 0 and 4 (0 = no spasm, 1 = mild, barely noticeable, 2 = mild, without functional impairment, 3 = moderate spasm, moderate functional impairment, 4 = severe incapacitating spasm). The JRS will be scored independently by two graders from a video clip of approximately 30-60 seconds in duration. Differences between the 2 scores will be arbitrated by a third reviewer.

    Secondary Outcome Measures

    Toronto (TWSTRS)
    TWSTRS instrument measuring clinical response. Scored between -1 and 5 (-1 = worse, 0 = no benefit, 1 = minimal or equivocal reduction in spasm, 2 = mild response with some reduction in spasm, 3 = moderate response with some reduction in spasm, 4 = marked reduction of spasm but spasm still present, 5 = major improvement with little or no residual spasm). The change between the 2 clinical activity visits (C1-C2) will be assessed.
    Blepharospasm Disability Index (BSDI)
    Measure of disability. The change between the 2 clinical activity visits (C1-C2) will be assessed.
    Craniocervical Dystonia Questionnaire (CDQ-24)
    Measure of quality of life. The change between the 2 clinical activity visits (C1-C2) will be assessed.
    Global Assessment Scale (GAS)
    To assess the overall status of the patient's disease. The GAS is determined by asking the patient the percentage of function the patient is experiencing. The analogue instrument ranges from "Free of complaints" on the left side to "Suffering extremely" on the right side of a line. Patients self-rate by marking where on the line best represents their current condition. The line measures 100 millimeters long. The mark is measured and the value recorded, ranging from 0 (Free of complaints) to 100 (Suffering extremely). Thus a lower value represents a better outcome. The change between the 2 clinical activity visits (C1-C2) will be assessed.
    Visual analogue scale (VAS) for pain
    VAS (range 0-10, no pain = 0, unbearable pain = 0) will be used to assess. The change between the 2 clinical activity visits (C1-C2) will be assessed. patients' perception of pain for each of the 2 injections patterns
    Ptosis monitoring
    Specifically, cropped photographs of both eyelids will be analysed using ImageJ (National Institutes of Health, USA). The Margin-Reflex-Distance 1 (MRD1) measurements will be calculated using the ImageJ software's line tool to capture the height of the upper eyelid and evaluate and quantify the development of any ptosis complications. The change between the 2 clinical activity visits (C1-C2) will be assessed.

    Full Information

    First Posted
    March 18, 2018
    Last Updated
    April 25, 2019
    Sponsor
    The University of Hong Kong
    Collaborators
    Food and Health Bureau, Hong Kong
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03508882
    Brief Title
    Pretarsal Versus Preseptal Botulinum Toxin for Patients With Eyelid Spasm
    Official Title
    Pretarsal Versus Preseptal Botulinum Toxin for Patients With Eyelid Spasm: a Randomized, Triple-blind, Placebo-controlled, Cross-over Clinical Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2019
    Overall Recruitment Status
    Completed
    Study Start Date
    July 1, 2015 (Actual)
    Primary Completion Date
    October 31, 2017 (Actual)
    Study Completion Date
    February 20, 2019 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    The University of Hong Kong
    Collaborators
    Food and Health Bureau, Hong Kong

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    A triple-masked placebo-controlled trial assessing the efficacy and safety of pretarsal versus preseptal botulinum toxin for patients with eyelid spasm. The investigators hypothesize injection of botulinum toxin into the pretarsal orbicularis oculi muscle will have greater clinical efficacy, better measured quality of life, fewer complications, and better cost effectiveness in comparison to a preseptal pattern of injection.
    Detailed Description
    The study design is a prospective, randomized, triple-blinded placebo controlled crossover trial. A computer-generated list of random numbers will be used for allocation of patients. The patients, treating physicians, and outcome assessors will be masked to the contents of the Botulinum Toxin Type A (BtA) and placebo syringe injections. The placebo will consist of vehicle only, which is the same sterile normal 0.9% saline used in reconstitution of the BtA. At month 6, each group will crossover and receive the alternative intervention. The primary outcome measure (JRS severity) will be the change as measured 1 month after the second cycle of each intervention. Secondary outcome measures include the TWSTRS (clinical response), Blepharospasm Disability Index (BSDI), CDQ-24 (quality of life), VAS (pain), and GAS (global) scores and incidence of side effects. The investigators plan to compare the outcome measures between groups with linear mixed models allowing for the crossover design. Data will be collected at each of the injection visits and at both of the clinical activity visits. The data will be processed by the research assistant and analysed by the project biostatistician. The investigators plan to compare the primary (JRS) and secondary outcome measures (TWSTRS, BSDI, CDQ-24, VAS, and GAS scores) between the Preseptal-pretarsal (Group 1) and the Pretarsal-preseptal (Group 2) allowing for the crossover design. Specifically, the investigators will use a 2-sample t-test to compare all values of the JRS in group 1 with all the values of the JRS in group 2. This will allow the investigators to determine whether carryover effects are present, and the investigators have specified a 3-month washout period between the first and second round of injections to minimise the chance of carryover effects. If carryover effects are present, the investigators will allow for these in further analysis. The investigators will then use linear mixed models to estimate the difference between the two interventions, allowing for the repeated measures, and if necessary for carryover effects. In secondary analyses, the investigators will evaluate the proportion of patients with relief of spasm, improvement in quality of life, and incidence of side effects, including eyelid ptosis measurements between the two interventions, using logistic regression. P values of 0.05 or less will be considered statistically significant. All analyses will be conducted under the principle of Intention to Treat, using multiple imputation to account for any missing data and to include all randomized patients in analysis.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Blepharospasm, Hemifacial Spasm, Botulinum Toxins, Type A
    Keywords
    Eyelid, Dystonia, Botulinum injection, Oculoplastics

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Crossover Assignment
    Masking
    ParticipantCare ProviderOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    100 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Preseptal-pretarsal
    Arm Type
    Active Comparator
    Arm Description
    The Preseptal-pretarsal group will receive injections of Botulinum Toxin Type A 100Unit/Vial (Product) in the preseptal site (Injection pattern A) and Saline Solution for Injection (placebo control) in the pretarsal site for 2 cycles at 3 months apart. Both groups will crossover and receive the alternative intervention. Hence in the second half of the trial, the Preseptal-pretarsal group will be injected with BtA in Pattern B and Pretarsal-preseptal group will receive Pattern A.
    Arm Title
    Pretarsal-preseptal
    Arm Type
    Active Comparator
    Arm Description
    The Pretarsal-preseptal group will initially receive injections Botulinum Toxin Type A 100Unit/Vial (Product) in the reverse with the intervention at the pretarsal site (Injection pattern B) for 2 cycles at 3 months apart. Groups 1 and 2 will crossover and receive the alternative intervention. Both groups will crossover and receive the alternative intervention. Hence in the second half of the trial, the Preseptal-pretarsal group will be injected with BtA in Pattern B and Pretarsal-preseptal group will receive Pattern A.
    Intervention Type
    Drug
    Intervention Name(s)
    Botulinum Toxin Type A 100Unit/Vial (Product)
    Other Intervention Name(s)
    Botox
    Intervention Description
    Botulinum Toxin Type A 100Unit/Vial (Product) comes as a dry powder and is routinely reconstituted with Saline Solution for Injection
    Intervention Type
    Drug
    Intervention Name(s)
    Saline Solution for Injection
    Other Intervention Name(s)
    Placebo
    Intervention Description
    The placebo consists of vehicle only. Saline Solution for Injection is the vehicle substance normally used to reconstitute Botulinum Toxin Type A (see 1st Intervention above).
    Primary Outcome Measure Information:
    Title
    Jankovic Rating Scale (JRS)
    Description
    The severity of the patient's spasm employing the widely used JRS scale. The JRS is scored between 0 and 4 (0 = no spasm, 1 = mild, barely noticeable, 2 = mild, without functional impairment, 3 = moderate spasm, moderate functional impairment, 4 = severe incapacitating spasm). The JRS will be scored independently by two graders from a video clip of approximately 30-60 seconds in duration. Differences between the 2 scores will be arbitrated by a third reviewer.
    Time Frame
    The videos will be taken at the clinical activity visits (C1 and C2) will be scheduled for months 4 and 10. The primary outcome measure will consist of the change from C1 to C2.
    Secondary Outcome Measure Information:
    Title
    Toronto (TWSTRS)
    Description
    TWSTRS instrument measuring clinical response. Scored between -1 and 5 (-1 = worse, 0 = no benefit, 1 = minimal or equivocal reduction in spasm, 2 = mild response with some reduction in spasm, 3 = moderate response with some reduction in spasm, 4 = marked reduction of spasm but spasm still present, 5 = major improvement with little or no residual spasm). The change between the 2 clinical activity visits (C1-C2) will be assessed.
    Time Frame
    C1 and C2 will take place at months 4 and 10.
    Title
    Blepharospasm Disability Index (BSDI)
    Description
    Measure of disability. The change between the 2 clinical activity visits (C1-C2) will be assessed.
    Time Frame
    C1 and C2 will take place at months 4 and 10.
    Title
    Craniocervical Dystonia Questionnaire (CDQ-24)
    Description
    Measure of quality of life. The change between the 2 clinical activity visits (C1-C2) will be assessed.
    Time Frame
    C1 and C2 will take place at months 4 and 10.
    Title
    Global Assessment Scale (GAS)
    Description
    To assess the overall status of the patient's disease. The GAS is determined by asking the patient the percentage of function the patient is experiencing. The analogue instrument ranges from "Free of complaints" on the left side to "Suffering extremely" on the right side of a line. Patients self-rate by marking where on the line best represents their current condition. The line measures 100 millimeters long. The mark is measured and the value recorded, ranging from 0 (Free of complaints) to 100 (Suffering extremely). Thus a lower value represents a better outcome. The change between the 2 clinical activity visits (C1-C2) will be assessed.
    Time Frame
    C1 and C2 will take place at months 4 and 10.
    Title
    Visual analogue scale (VAS) for pain
    Description
    VAS (range 0-10, no pain = 0, unbearable pain = 0) will be used to assess. The change between the 2 clinical activity visits (C1-C2) will be assessed. patients' perception of pain for each of the 2 injections patterns
    Time Frame
    Measured at each injection visit (months 0, 3, 6, and 9).
    Title
    Ptosis monitoring
    Description
    Specifically, cropped photographs of both eyelids will be analysed using ImageJ (National Institutes of Health, USA). The Margin-Reflex-Distance 1 (MRD1) measurements will be calculated using the ImageJ software's line tool to capture the height of the upper eyelid and evaluate and quantify the development of any ptosis complications. The change between the 2 clinical activity visits (C1-C2) will be assessed.
    Time Frame
    C1 and C2 will take place at months 4 and 10.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients over 18 years-of-age Clinical diagnosis eyelid dystonia, consisting of either blepharospasm or hemifacial spasm Patient wish to have treatment with botulinum toxin type A (BtA). Exclusion Criteria: Patients unable to express their symptoms or history to the extent that they are not able to complete the study questionnaires, such as those suffering from dementia. Existence of potential contraindications to BtA treatment: Pregnancy Breastfeeding Prior allergic reaction Active infection or inflammation in the treatment area Neuromuscular and peripheral neuropathic disease Concomitant aminoglycoside therapy Patients with poor or unstable general health with activities of daily living severely affected by non-dystonia confounding factors, such as hospitalized or bed bound patients.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Marcus M Marcet, MD
    Organizational Affiliation
    The University of Hong Kong
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
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    Links:
    URL
    https://www.asoprs.org/eyelid-spasms
    Description
    General information about eyelid spasms and treatment

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    Pretarsal Versus Preseptal Botulinum Toxin for Patients With Eyelid Spasm

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