A Study of Acetyl Hexapeptide-8 (AH8) in Treatment of Blepharospasm

Study Overview
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Brief Summary
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Background: Blepharospasm is caused by excessive contraction of the muscles that close the eye. It can be treated with injections of botulinum neurotoxin (BoNT), which works by weakening those muscles. Acetyl Hexapeptide-8 (AH-8) is the active ingredient in a number of cosmetic creams used to treat wrinkles, and is marketed under the trade name Argireline(Copyright). Like BoNT, AH-8 works to weaken the muscles, but is available as a skin cream instead of an injection. AH-8 has never been used to treat people with blepharospasm. Objectives: - To determine if AH-8 can be used as part of a treatment regimen for blepharospasm. Eligibility: - Individuals 18 years of age and older who have blepharospasm and have been receiving successful treatment with botulinum toxin injections. Design: Participants will be involved in the study for a maximum of 7 months. Patients will have a complete physical and neurological exam, and will be asked questions about their blepharospasm. Patients will then receive BoNT injections in the same areas of the muscle around the eye and at the same doses that have been effective previously. After the injections, patients will receive a container of either the active cream (with AH-8) or cream without AH-8, and will be instructed on how to apply it. Patients will return 1 month after the first visit for another neurologic exam and questions, and will be asked about any side effects. Another supply of cream will be given. Five additional visits will take place on a monthly basis, and patients will be given additional supplies of the cream as needed. Patients will stop participating in the study if they require another BoNT injection for blepharospasm. The study will end after 7 months.

Detailed Description
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OBJECTIVE: To study the efficacy of cutaneous application of Acetyl Hexapeptide-8 (AH8) in the therapy of blepharospasm. STUDY POPULATION: 22 patients with blepharospasm. DESIGN: This will be a double blind, placebo-controlled trial. Patients receiving treatment of blepharospasm with botulinum neurotoxin (BoNT) will be recruited. They will receive either the study substance or a placebo cream containing the emulsion but no active substance, in twice daily applications to the eyelids beginning the day following a BoNT injection treatment. They will continue to apply the cream and we will record the time until their condition worsens back to baseline following benefit from the injections, hypothesizing that the cream application will prolong the time until the need for the next injection by at least 3 months. OUTCOME MEASURES:: Primary: time until the Jankovic Blepharospasm Rating Scale (JBRS) reverts back to baseline. Secondary: Change in the JBRS at 6 months; Change in the JBRS at 7 months if not receiving BoNT; Change in the JBRS at 3 months; Change in the Blepharospasm Disability Scale at 6 months

Official Title
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A Study of Acetyl Hexapeptide-8 (AH8) in Treatment of Blepharospasm

Conditions
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Focal Dystonia

Intervention / Treatment
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* Drug: Acetyl-Hexapeptide Topical Treatment
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Age above 18 years Diagnosis of PB made by a Movement Disorders Neurologist Severity of PB prompting the need for treatment as determined by patient subjective assessment. JBRS of at least 3 at initial visit. BDS of at least 8 at the entry visit. At least three prior successful injectable BoNT treatments, with stable interval between injections of 3 months (ie duration of response of 3 months). EXCLUSION CRITERIA: Pregnant women Blepharospasm associated with a different Neurologic condition, including but not limited to generalyzed dystonia, a parkinsonian syndrome, or major brain structural abnormality, as evidenced by Neurologic exam and/or review of records Skin condition resulting in loss of integrity of the skin overlying the OO or potentially interfering with cream absorption. Medical condition impairing the patient's ability to comply with the study protocol or to perform daily applications of the cream as instructed Abnormally long or short response to BoNT treatment in the past, ie duration of PB relief with BoNT greater than 4 months or less than 2 months. Allergy to any component of the study or placebo cream. Known or observed eye pathology.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: active<br>AH-8 containing topical intervention | Drug: Acetyl-Hexapeptide Topical Treatment<br>* AH-8 containing topical treatment<br>|
| Placebo Comparator: placebo<br>topical intervention WITHOUT AH-8 | Drug: placebo<br>* topical treatment NOT containing AH-8<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Until Jankovic Blepharospasm Rating Scale (JBRS) Reverts Back to Baseline | The JBRS is a severity scale for blepharospasm, ranging from 0 (no symptoms) to 8 (the most severe symptoms, functionally blind). It includes measures of blink frequency and severity of abnormal eye closure. The scale was measured at baseline (before intervention) and followed over time. Return to baseline value represents loss of benefit from BoNT injection. The time to return to baseline JBRS is an indication of added benefit from the topical intervention. | 3-7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the JBRS at 3 Months | The JBRS is a severity scale for blepharospasm, ranging from 0 (no symptoms) to 8 (the most severe symptoms, functionally blind). It includes measures of blink frequency and severity of abnormal eye closure. The scale was measured at baseline (before intervention) and followed over time. | baseline to 3 months | 
| % Blepharospasm Disability Scale (BDS) Change at 3 Months | % BDS change at 3 months. The BDS is a quality of life scale ranging from 0 (no symptoms) to 26 (maximum impact of symptoms on quality of life). The questions are specific for impairment related to blepharospasm. We compared the percentage change over three months in the active and placebo arms. | baseline to 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dystonia, Blepharospasm, Botulinum Toxin, Treatment, Clinical Trial, Focal Dystonia