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

• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00942851
• Collaborator: BCN Peptides (Industry)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 15
• Patients Per Site Per Month: 1.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Focal Dystonia	Drug: Acetyl-Hexapeptide Topical Treatment; Drug: placebo	Phase 1/Phase 2

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Study of Acetyl Hexapeptide-8 (AH8) in Treatment of Blepharospasm
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: active AH-8 containing topical intervention	Drug: Acetyl-Hexapeptide Topical Treatment; AH-8 containing topical treatment
Placebo Comparator: placebo topical intervention WITHOUT AH-8	Drug: placebo; topical treatment NOT containing AH-8

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. % 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS)
• BCN Peptides

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ben Simon GJ, McCann JD. Benign essential blepharospasm. Int Ophthalmol Clin. 2005 Summer;45(3):49-75. Review.
• Defazio G, Livrea P. Epidemiology of primary blepharospasm. Mov Disord. 2002 Jan;17(1):7-12. Review.
• Defazio G, Livrea P. Primary blepharospasm: diagnosis and management. Drugs. 2004;64(3):237-44. Review.

• Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
• ClinicalTrials.gov Identifier: NCT00942851
• Other Study ID Numbers: 090193; 09-N-0193
• First Posted: Jul 21, 2009
• Last Update Posted: Sep 6, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by National Institute of Neurological Disorders and Stroke (NINDS): Dystonia; Blepharospasm; Botulinum Toxin; Treatment; Clinical Trial; Focal Dystonia
• Additional relevant MeSH terms: Dystonia; Dystonic Disorders; Blepharospasm

Study Results

Participant Flow

Arm/Group Title	Active	Placebo
Arm/Group Description	Topical intervention agent containing AH8 0.005% Twice daily application to the eyelids in standardized fashion.	Topical intervention agent WITHOUT AH-8. Identically appearing cream without the active ingredient. Twice daily application to the eyelids in standardized fashion.
Period Title: Overall Study
STARTED	12	12
COMPLETED	12	11
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Active	Placebo	Total
Arm/Group Description	AH-8 containing topical intervention	topical intervention WITHOUT AH-8	Total of all reporting groups
Overall Participants	12	12	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 83.3%	11 91.7%	21 87.5%
>=65 years	2 16.7%	1 8.3%	3 12.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.59 (8.46)	55.87 (8.25)	56.73 (8.22)
Sex: Female, Male (Count of Participants)
Female	12 100%	2 16.7%	14 58.3%
Male	0 0%	10 83.3%	10 41.7%
Region of Enrollment (participants) [Number]
United States	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Time Until Jankovic Blepharospasm Rating Scale (JBRS) Reverts Back to Baseline
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Ingredient- AH8	Placebo
Arm/Group Description	subjects receiving active intervention, ie topical cream containing 0.005% AH-8	subjects receiving placebo intervention, ie identically-appearing topical cream without AH-8 content
Measure Participants	12	11
Mean (Standard Deviation) [month]	3.71 (1.48)	3.03 (.23)

2. Secondary Outcome

Title	Change in the JBRS at 3 Months
Description	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

Outcome Measure Data

Analysis Population Description

One placebo arm participant dropped out due to unrelated personal problems

Arm/Group Title	Active Ingredient- AH8	Placebo
Arm/Group Description
Measure Participants	12	11
Mean (Standard Deviation) [points]	1.09 (0.7)	0.92 (2.07)

3. Secondary Outcome

Title	% Blepharospasm Disability Scale (BDS) Change at 3 Months
Description	% 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

Outcome Measure Data

Analysis Population Description

One placebo arm participant discontinued study due to unrelated personal problems

Arm/Group Title	Active	Placebo
Arm/Group Description	AH-8 containing topical intervention	topical intervention WITHOUT AH-8
Measure Participants	12	11
Mean (Standard Deviation) [percentage change]	30.89 (37.3)	32.32 (31.13)

Adverse Events

Arm/Group Title	Active		Placebo
Arm/Group Description	AH-8 containing topical intervention		topical intervention WITHOUT AH-8
All Cause Mortality
	Active		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Active		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Active		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/12 (16.7%)		2/12 (16.7%)
Skin and subcutaneous tissue disorders
eyelid irritation	2/12 (16.7%)	2	2/12 (16.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.