Focal Dystonia
Conditions
Keywords
Dystonia, Blepharospasm, Botulinum Toxin, Treatment, Clinical Trial, Focal Dystonia
Brief summary
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
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
Interventions
DRUGAcetyl-Hexapeptide Topical Treatment
AH-8 containing topical treatment
DRUGplacebo
topical treatment NOT containing AH-8
Sponsors
BCN Peptides
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: 1. Age above 18 years 2. Diagnosis of PB made by a Movement Disorders Neurologist 3. Severity of PB prompting the need for treatment as determined by patient subjective assessment. 4. JBRS of at least 3 at initial visit. 5. BDS of at least 8 at the entry visit. 6. 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
1. Pregnant women 2. 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 3. Skin condition resulting in loss of integrity of the skin overlying the OO or potentially interfering with cream absorption. 4. Medical condition impairing the patient's ability to comply with the study protocol or to perform daily applications of the cream as instructed 5. 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. 6. Allergy to any component of the study or placebo cream. 7. Known or observed eye pathology.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Until Jankovic Blepharospasm Rating Scale (JBRS) Reverts Back to Baseline | 3-7 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. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the JBRS at 3 Months | baseline to 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. |
| % Blepharospasm Disability Scale (BDS) Change at 3 Months | baseline to 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active AH-8 containing topical intervention | 12 |
| Placebo topical intervention WITHOUT AH-8 | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Placebo | Active | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 10 Participants | 21 Participants |
| Age Continuous | 55.87 years STANDARD_DEVIATION 8.25 | 57.59 years STANDARD_DEVIATION 8.46 | 56.73 years STANDARD_DEVIATION 8.22 |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 2 Participants | 12 Participants | 14 Participants |
| Sex: Female, Male Male | 10 Participants | 0 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 12 | 2 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
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.
Time frame: 3-7 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Ingredient- AH8 | Time Until Jankovic Blepharospasm Rating Scale (JBRS) Reverts Back to Baseline | 3.71 month | Standard Deviation 1.48 |
| Placebo | Time Until Jankovic Blepharospasm Rating Scale (JBRS) Reverts Back to Baseline | 3.03 month | Standard Deviation 0.23 |
Secondary
% 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.
Time frame: baseline to 3 months
Population: One placebo arm participant discontinued study due to unrelated personal problems
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Ingredient- AH8 | % Blepharospasm Disability Scale (BDS) Change at 3 Months | 30.89 percentage change | Standard Deviation 37.3 |
| Placebo | % Blepharospasm Disability Scale (BDS) Change at 3 Months | 32.32 percentage change | Standard Deviation 31.13 |
Secondary
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.
Time frame: baseline to 3 months
Population: One placebo arm participant dropped out due to unrelated personal problems
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Ingredient- AH8 | Change in the JBRS at 3 Months | 1.09 points | Standard Deviation 0.7 |
| Placebo | Change in the JBRS at 3 Months | 0.92 points | Standard Deviation 2.07 |