Acetyl Hexapeptide-8 for Blepharospasm

NCT01750346 | Terminated Phase 2 Results

• 2 other identifiers: 13002213-N-0022
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Focal Dystonia

Keywords

Blepharospasm; Treatment; Dystonia; Acetyl-Hexapeptide

Outcome Measures

Primary Outcomes (1)

• 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 (6)

• The Jankovic Blepharospasm Rating Scale at 1 Month

  1 month

• The Blepharospasm Disability Scale at 1 Month

  1 month

• The Blepharospasm Disability Scale at 2 Months

  2 months

• The Jankovic Blepharospasm Rating Scale at 3 Months

  3 months

• The Jankovic Blepharospasm Rating Scale at 6 Months

  6 months

Study Arms (3)

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

Interventions

Topical acetyl hexapeptide-8 DRUG

0.025% AH-8; 0.05% AH-8

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 15970766 BACKGROUND

• Defazio G, Livrea P. Primary blepharospasm: diagnosis and management. Drugs. 2004;64(3):237-44. doi: 10.2165/00003495-200464030-00002.

  PMID: 14871168 BACKGROUND

• Defazio G, Livrea P. Epidemiology of primary blepharospasm. Mov Disord. 2002 Jan;17(1):7-12. doi: 10.1002/mds.1275.

  PMID: 11835433 BACKGROUND

MeSH Terms

Conditions

Dystonic Disorders; Blepharospasm; Dystonia

Interventions

acetyl-glutamyl-glutamyl-methionyl-glutaminyl-arginyl-argininamide

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Eyelid Diseases; Eye Diseases; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Codrin Lungu
• Organization: National Institutes of Health

lunguci@ninds.nih.gov

301-402-0976

Study Officials

• Codrin I Lungu, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2012
• First Posted: December 17, 2012
• Study Start: November 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: November 10, 2016
• Results First Posted: November 10, 2016

Record last verified: 2016-09

Locations

US (1)