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
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.
Study Phase
Phase 4
Study Type
Interventional
Primary Outcome
Jankovic Rating Scale (JRS)
Secondary Outcome
Toronto (TWSTRS)
Condition
Blepharospasm
Intervention
Botulinum Toxin Type A 100Unit/Vial (Product)
Study Arms / Comparison Groups
Preseptal-pretarsal
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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
100
Start Date
July 1, 2015
Completion Date
February 20, 2019
Primary Completion Date
October 31, 2017
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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Marcus M Marcet, MD, ,
Administrative Informations
NCT ID
NCT03508882
Organization ID
HMRF Project No.: 12133171
Secondary IDs
Protocol : MMBT; v1.3;1Mar16
Responsible Party
Principal Investigator
Study Sponsor
The University of Hong Kong
Collaborators
Food and Health Bureau, Hong Kong
Study Sponsor
Marcus M Marcet, MD, Principal Investigator, The University of Hong Kong
Verification Date
April 2019