Acetyl Hexapeptide-8 for Blepharospasm
| Status: | Completed |
|---|---|
| Conditions: | Neurology, Orthopedic |
| Therapuetic Areas: | Neurology, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 7/11/2015 |
| Start Date: | November 2012 |
| End Date: | December 2015 |
| Contact: | Elaine P Considine, R.N. |
| Email: | considinee@ninds.nih.gov |
| Phone: | (301) 435-8518 |
Placebo Controlled Double Blind Study of Acetyl Hexapeptide-8 in Treatment of Blepharospasm
Background:
- Blepharospasm is caused by excessive contraction of the muscles that close the eye. One
treatment is botulinum neurotoxin (BoNT), which works by weakening those muscles. Like BoNT,
acetyl hexapeptide-8 (AH-8) works to weaken the muscles, but is available as a skin cream.
AH-8 is the active ingredient in a number of cosmetic creams used to treat wrinkles.
Researchers thought that AH-8 cream could be used to treat blepharospasm, but the original
dose studied was not very effective. They want to try a higher dose of AH-8 in a cream to
see if it can be a more effective treatment.
Objectives:
- To see if AH-8 cream can improve the symptoms of blepharospasm.
Eligibility:
- Individuals at least 18 years of age who have blepharospasm that is severe enough to
require treatment.
Design:
- This study will involve up to eight study visits.
- Participants will be screened with a physical exam and medical history. They will
answer questions about their symptoms. They will also have a blink test to see how
severe the blepharospasm is. At this visit, participants will receive one of three
types of cream. One cream will have a low dose of AH-8, one will have a higher dose of
AH-8, and the other will be a placebo (no AH-8).
- One month later, participants will have a followup visit, with tests similar to the
first visit. They will also receive more of the cream.
- One month later, participants will have another visit with the same tests. They will be
videotaped at this visit to study their facial movements. Those who have responded to
the treatment will continue to use the cream. Those who have not responded will be
offered the chance to have BoNT injections, and will stop taking the cream.
- One month later, participants who had BoNT injections will have a final visit to check
for possible side effects. Those who continued to take the cream will continue on the
study.
- The fifth and sixth visits will involve the same tests as before. At the seventh visit,
remaining participants will be offered the chance to have BoNT injections, and will
stop taking the cream.
- The final visit will check for any side effects from the cream or the injections.
- Blepharospasm is caused by excessive contraction of the muscles that close the eye. One
treatment is botulinum neurotoxin (BoNT), which works by weakening those muscles. Like BoNT,
acetyl hexapeptide-8 (AH-8) works to weaken the muscles, but is available as a skin cream.
AH-8 is the active ingredient in a number of cosmetic creams used to treat wrinkles.
Researchers thought that AH-8 cream could be used to treat blepharospasm, but the original
dose studied was not very effective. They want to try a higher dose of AH-8 in a cream to
see if it can be a more effective treatment.
Objectives:
- To see if AH-8 cream can improve the symptoms of blepharospasm.
Eligibility:
- Individuals at least 18 years of age who have blepharospasm that is severe enough to
require treatment.
Design:
- This study will involve up to eight study visits.
- Participants will be screened with a physical exam and medical history. They will
answer questions about their symptoms. They will also have a blink test to see how
severe the blepharospasm is. At this visit, participants will receive one of three
types of cream. One cream will have a low dose of AH-8, one will have a higher dose of
AH-8, and the other will be a placebo (no AH-8).
- One month later, participants will have a followup visit, with tests similar to the
first visit. They will also receive more of the cream.
- One month later, participants will have another visit with the same tests. They will be
videotaped at this visit to study their facial movements. Those who have responded to
the treatment will continue to use the cream. Those who have not responded will be
offered the chance to have BoNT injections, and will stop taking the cream.
- One month later, participants who had BoNT injections will have a final visit to check
for possible side effects. Those who continued to take the cream will continue on the
study.
- The fifth and sixth visits will involve the same tests as before. At the seventh visit,
remaining participants will be offered the chance to have BoNT injections, and will
stop taking the cream.
- The final visit will check for any side effects from the cream or the injections.
OBJECTIVE:
Test the efficacy of topical AH-8 in blepharospasm treatment.
DESIGN:
This is a randomized, double blind, placebo-controlled study, phase II single center
clinical trial. Patients with primary blepharospasm at least 4 months off BoNT therapy with
no benefit from last BoNT injection by history and self assesment will be included. We will
use 3 study arms placebo and 2 different doses (as concentrations of the AH-8 active
substance in the topical preparation). An extension phase is planned after the initial
phase.
The patients will have a baseline screening visit, including measurement of the outcome
variables, then begin the study intervention. They will have 2 subsequent visits at month 1
and month 2. After this visit, the patients who do not have significant benefit and wish to
have an alternative therapy (GROUP 1) will receive BoNT injections according to best
practice standards. These patients will then be assessed 1 month later (peak effect of BoNT
therapy) and the effect will be compared with the AH-8 effect. The patients who have
significant benefit (GROUP 2) will continue therapy for another 4 months (total of 6
months), and will have another assessment at that point. Afterwards the patients will be
offered BoNT injections according to best practice standards, similar to Group 1 above, and
another assessment will be made one month later (month 7) to compare the effects with AH-8
effects.
OUTCOME MEASURES:
Primary outcome variable: the Jankovic Blepharospasm Rating Scale at month 2.
Secondary outcome variables:
- the Jankovic Blepharospasm Rating Scale at month 1
- the Blepharospasm Disability Scale at month 1
- the Blepharospasm Disability Scale at month 2
- the difference in JBRS at month 3 time point (after BoNT injection) in patients
receiving BoNT
- JBRS score at 6 months for patients not receiving BoNT at month 2 (Group 2)
- the difference in JBRS between month 6 and month 7 time point (after BoNT
injection) in Group 2 patients
- Blink reflex measures at month 2
Non-parametric comparison (Wilcoxon Mann-Whitney test) of the primary and secondary
variables before and after the intervention will be used for statistical analysis.
Additional multivariate analysis will explore the influence of other factors (age, gender,
disease duration).
Interventions and Duration
Twice daily application of active substance or placebo. Two active substance
concentrations, 0.025% and 0.05% AH-8 will be used.
Each subject will be in the study a total of at least 3 months, followed by additional up to
4 months in the second phase for the group 2 patients.
Sample Size and Population
There will be 8 patients per arm, for a total study population of 24. The power calculation
for a power of 80%, for a 2-tailed alpha of 0.05, to be able to detect a change of 2 points
on the JBRS requires 8 patients per arm. This calculation was based on independent
calculation for each dose of the active agent against placebo.
The subjects included will be patients with primary blepharospasm, not currently treated
with BoNT (de novo diagnosed patients), but who subjectively express a wish for treatment
intervention, with at least one year history from symptom onset, without perceived active
change in symptoms by history. Patients with blepharospasm as part of a generalized dystonia
or due to a different neurologic condition will be excluded.
Randomization and blinding to be performed by the NIH research pharmacy.
Test the efficacy of topical AH-8 in blepharospasm treatment.
DESIGN:
This is a randomized, double blind, placebo-controlled study, phase II single center
clinical trial. Patients with primary blepharospasm at least 4 months off BoNT therapy with
no benefit from last BoNT injection by history and self assesment will be included. We will
use 3 study arms placebo and 2 different doses (as concentrations of the AH-8 active
substance in the topical preparation). An extension phase is planned after the initial
phase.
The patients will have a baseline screening visit, including measurement of the outcome
variables, then begin the study intervention. They will have 2 subsequent visits at month 1
and month 2. After this visit, the patients who do not have significant benefit and wish to
have an alternative therapy (GROUP 1) will receive BoNT injections according to best
practice standards. These patients will then be assessed 1 month later (peak effect of BoNT
therapy) and the effect will be compared with the AH-8 effect. The patients who have
significant benefit (GROUP 2) will continue therapy for another 4 months (total of 6
months), and will have another assessment at that point. Afterwards the patients will be
offered BoNT injections according to best practice standards, similar to Group 1 above, and
another assessment will be made one month later (month 7) to compare the effects with AH-8
effects.
OUTCOME MEASURES:
Primary outcome variable: the Jankovic Blepharospasm Rating Scale at month 2.
Secondary outcome variables:
- the Jankovic Blepharospasm Rating Scale at month 1
- the Blepharospasm Disability Scale at month 1
- the Blepharospasm Disability Scale at month 2
- the difference in JBRS at month 3 time point (after BoNT injection) in patients
receiving BoNT
- JBRS score at 6 months for patients not receiving BoNT at month 2 (Group 2)
- the difference in JBRS between month 6 and month 7 time point (after BoNT
injection) in Group 2 patients
- Blink reflex measures at month 2
Non-parametric comparison (Wilcoxon Mann-Whitney test) of the primary and secondary
variables before and after the intervention will be used for statistical analysis.
Additional multivariate analysis will explore the influence of other factors (age, gender,
disease duration).
Interventions and Duration
Twice daily application of active substance or placebo. Two active substance
concentrations, 0.025% and 0.05% AH-8 will be used.
Each subject will be in the study a total of at least 3 months, followed by additional up to
4 months in the second phase for the group 2 patients.
Sample Size and Population
There will be 8 patients per arm, for a total study population of 24. The power calculation
for a power of 80%, for a 2-tailed alpha of 0.05, to be able to detect a change of 2 points
on the JBRS requires 8 patients per arm. This calculation was based on independent
calculation for each dose of the active agent against placebo.
The subjects included will be patients with primary blepharospasm, not currently treated
with BoNT (de novo diagnosed patients), but who subjectively express a wish for treatment
intervention, with at least one year history from symptom onset, without perceived active
change in symptoms by history. Patients with blepharospasm as part of a generalized dystonia
or due to a different neurologic condition will be excluded.
Randomization and blinding to be performed by the NIH research pharmacy.
- INCLUSION CRITERIA:
- Primary blepharospasm diagnosed or confirmed by a Movement Disorders Neurologist,
confirmed at the initial visit by a study investigator.
- Individuals off BoNT therapy for at least 4 months will be eligible for this study.
- Severity prompting need for treatment as determined by clinical judgment
- At least a score of 4 on the JBRS
- At least a score of 8 on the BDS
- Duration of symptoms of at least 1 year, without subjective active progression
by patient report
- Concomitant therapy allowed, except injectable BoNT therapy, provided the doses
remain stable throughout the study period
- Adult patients (> 18)
EXCLUSION CRITERIA:
- Blepharospasm associated with generalized or extensive regional dystonia
- Medical condition impairing the patient's ability to comply with the study protocol
or to perform daily applications of the cream as instructed as judged by
recruiting physician
- Local eyelid pathology precluding topical treatment
- Received BoNT within 4 months prior to enrollment
- Continued benefit from a prior BoNT injection (by history and self assesment) Current
use of cosmetic wrinkle creams
- Prior myectomy procedure excluded
- Pregnant women excluded. Barrier contraception will be used throughout the study for
women of childbearing age, as it is not known how the use of hormonal contraceptives
may interact with the study substance. Menopausal status will be determined by the
CNS IRB criteria. In women of childbearing potential, a pregnancy test will be
performed at the initial visit and periodically every 2 months for the duration of
the study. Barrier contraception will be deemed necessary for the duration of the
study and none after.
- Use of other treatments for blepharospasm allowed if the doses remain constant
- Allergy/sensitivity to study substance or vehicle.
- Active drug or alcohol abuse or dependence
- Patients with uncontrolled co-existing medical conditions: uncontrolled systemic
hypertension with values above 170/100; active heart disease needing immediate
intervention; active respiratory disease needing intervention; known or observed eye
pathology; any condition that would render the patient unable to safely cooperate
with the study tests as judged by the screening physician
- Cognitive inability to independently use cr(SqrRoot)(Registered Trademark)me use
safely.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
301-496-4000
National Institutes of Health Clinical Center The National Institutes of Health (NIH) Clinical Center in...
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