Acetyl Hexapeptide-8 for Blepharospasm | NCT01750346

NCT01750346

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
13-N-0022

Status Module

Description Module

Brief Summary

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.

Detailed Description

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.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
0.05% AH-8	Active Comparator	Participants in the 0.05% AH-8 arm received the higher dose of the study drug, Acetyl Hexapeptide 8 (AH-8), which is sold under the brand name, Argireline.	Drug: Topical acetyl hexapeptide-8
0.025% AH-8	Active Comparator	Participants in the 0.025% AH-8 arm received the lower dose of the study drug, Acetyl Hexapeptide 8 (AH-8), which is sold under the brand name, Argireline.	Drug: Topical acetyl hexapeptide-8
Placebo	Placebo Comparator	Participants in the Placebo arm received the placebo.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Topical acetyl hexapeptide-8	Drug		0.025% AH-8 0.05% AH-8
Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
The Jankovic Blepharospasm Rating Scale at 2 Month	The Jankovic Blepharospasm Rating Scale (JBRS) at 2 months from the start of the study drug or placebo. The JBRS is a clinical scale measuring the severity and frequency of blepharospasm. Severity and frequency are rated on a 5-point scales ranging from 0 to 4, where 0 indicates no symptoms and 4 indicates the most severe or frequent symptoms (Severity: severe, incapacitating spasm of eyelids and possibly other facial muscles; Frequency: Functionally "blind" due to persistent eye closure (blepharospasm) more than 50% of the waking time.) A total score is obtained by adding the severity and frequency subscale scores with total scores ranging from 0 to 8.	2 months

Secondary Outcomes

Measure	Description	Time Frame
The Jankovic Blepharospasm Rating Scale at 1 Month	The Jankovic Blepharospasm Rating Scale (JBRS) was measured at 1 month from the start of the study drug or placebo. The JBRS is a clinical scale measuring the severity and frequency of blepharospasm. Severity and frequency are rated on a 5-point scales ranging from 0 to 4, where 0 indicates no symptoms and 4 indicates the most severe or frequent symptoms (Severity: severe, incapacitating spasm of eyelids and possibly other facial muscles; Frequency: Functionally "blind" due to persistent eye closure (blepharospasm) more than 50% of the waking time.) A total score is obtained by adding the severity and frequency subscale scores with total scores ranging from 0 to 8.

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
Codrin I Lungu, M.D.	National Institute of Neurological Disorders and Stroke (NINDS)	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
National Institutes of Health Clinical Center, 9000 Rockville Pike		Bethesda	Maryland	20892	United States

PubMed Identifier	Type	Citation	Retractions
15970766	Background	Ben Simon GJ, McCann JD. Benign essential blepharospasm. Int Ophthalmol Clin. 2005 Summer;45(3):49-75. doi: 10.1097/01.iio.0000167238.26526.a8. No abstract available.
14871168	Background	Defazio G, Livrea P. Primary blepharospasm: diagnosis and management. Drugs. 2004;64(3):237-44. doi: 10.2165/00003495-200464030-00002.

ID	Title	Description
FG000	0.05% AH-8	Participants in the 0.05% AH-8 arm received the higher dose of the study drug, Acetyl Hexapeptide 8 (AH-8), which is sold under the band name, Argireline.
FG001	0.025% AH-8	Participants in the 0.025% AH-8 arm received the lower dose of the study drug, Acetyl Hexapeptide 8 (AH-8), which is sold under the band name, Argireline.
FG002	Placebo	Participants in the Placebo arm received the placebo.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	0.05% AH-8	Participants in the 0.05% AH-8 arm received the higher dose of the study drug, Acetyl Hexapeptide 8 (AH-8), which is sold under the band name, Argireline.
BG001	0.025% AH-8

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

The Jankovic Blepharospasm Rating Scale at 2 Month

The Jankovic Blepharospasm Rating Scale (JBRS) at 2 months from the start of the study drug or placebo. The JBRS is a clinical scale measuring the severity and frequency of blepharospasm. Severity and frequency are rated on a 5-point scales ranging from 0 to 4, where 0 indicates no symptoms and 4 indicates the most severe or frequent symptoms (Severity: severe, incapacitating spasm of eyelids and possibly other facial muscles; Frequency: Functionally "blind" due to persistent eye closure (blepharospasm) more than 50% of the waking time.) A total score is obtained by adding the severity and frequency subscale scores with total scores ranging from 0 to 8.

One participant in the 0.05% AH-8 arm was withdrawn due to development of blepharitis.

Posted

Mean

Full Range

units on a scale

2 months

ID	Title	Description
OG000	0.05% AH-8	Participants in the 0.05% AH-8 arm received the higher dose of the study drug, Acetyl Hexapeptide 8 (AH-8), which is sold under the band name, Argireline.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	0.05% AH-8	Participants in the 0.05% AH-8 arm received the higher dose of the study drug, Acetyl Hexapeptide 8 (AH-8), which is sold under the band name, Argireline. Topical acetyl hexapeptide-8

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Automobile accident	General disorders			Subject was the driver involved in automobile accident. Subject was on study medication and reported that worsening of blepharospasm may have contributed to accident.

ID	Term
D020821	Dystonic Disorders
D001764	Blepharospasm
D004421	Dystonia

ID	Term
D009069	Movement Disorders
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D005141	Eyelid Diseases