Pretarsal Versus Preseptal Botulinum Toxin for Patients With Eyelid Spasm

NCT03508882 | Completed Phase 4

• 2 other identifiers: HMRF Project No.: 12133171Protocol : MMBT; v1.3;1Mar16
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

A triple-masked placebo-controlled trial assessing the efficacy and safety of pretarsal versus preseptal botulinum toxin for patients with eyelid spasm. The investigators hypothesize injection of botulinum toxin into the pretarsal orbicularis oculi muscle will have greater clinical efficacy, better measured quality of life, fewer complications, and better cost effectiveness in comparison to a preseptal pattern of injection.

Conditions

Blepharospasm; Hemifacial Spasm; Botulinum Toxins, Type A

Keywords

Eyelid; Dystonia; Botulinum injection; Oculoplastics

Outcome Measures

Primary Outcomes (1)

• Jankovic Rating Scale (JRS)

  The severity of the patient's spasm employing the widely used JRS scale. The JRS is scored between 0 and 4 (0 = no spasm, 1 = mild, barely noticeable, 2 = mild, without functional impairment, 3 = moderate spasm, moderate functional impairment, 4 = severe incapacitating spasm). The JRS will be scored independently by two graders from a video clip of approximately 30-60 seconds in duration. Differences between the 2 scores will be arbitrated by a third reviewer.

  The videos will be taken at the clinical activity visits (C1 and C2) will be scheduled for months 4 and 10. The primary outcome measure will consist of the change from C1 to C2.

Secondary Outcomes (6)

• Toronto (TWSTRS)

  C1 and C2 will take place at months 4 and 10.

• Blepharospasm Disability Index (BSDI)

  C1 and C2 will take place at months 4 and 10.

• Craniocervical Dystonia Questionnaire (CDQ-24)

  C1 and C2 will take place at months 4 and 10.

• Global Assessment Scale (GAS)

  C1 and C2 will take place at months 4 and 10.

• Visual analogue scale (VAS) for pain

  Measured at each injection visit (months 0, 3, 6, and 9).

Study Arms (2)

Preseptal-pretarsal

ACTIVE COMPARATOR

The Preseptal-pretarsal group will receive injections of Botulinum Toxin Type A 100Unit/Vial (Product) in the preseptal site (Injection pattern A) and Saline Solution for Injection (placebo control) in the pretarsal site for 2 cycles at 3 months apart. Both groups will crossover and receive the alternative intervention. Hence in the second half of the trial, the Preseptal-pretarsal group will be injected with BtA in Pattern B and Pretarsal-preseptal group will receive Pattern A.

Drug: Botulinum Toxin Type A 100Unit/Vial (Product); Drug: Saline Solution for Injection

Pretarsal-preseptal

ACTIVE COMPARATOR

The Pretarsal-preseptal group will initially receive injections Botulinum Toxin Type A 100Unit/Vial (Product) in the reverse with the intervention at the pretarsal site (Injection pattern B) for 2 cycles at 3 months apart. Groups 1 and 2 will crossover and receive the alternative intervention. Both groups will crossover and receive the alternative intervention. Hence in the second half of the trial, the Preseptal-pretarsal group will be injected with BtA in Pattern B and Pretarsal-preseptal group will receive Pattern A.

Drug: Botulinum Toxin Type A 100Unit/Vial (Product); Drug: Saline Solution for Injection

Interventions

Botulinum Toxin Type A 100Unit/Vial (Product) DRUG

Botulinum Toxin Type A 100Unit/Vial (Product) comes as a dry powder and is routinely reconstituted with Saline Solution for Injection

Also known as: Botox

Preseptal-pretarsal; Pretarsal-preseptal

Saline Solution for Injection DRUG

The placebo consists of vehicle only. Saline Solution for Injection is the vehicle substance normally used to reconstitute Botulinum Toxin Type A (see 1st Intervention above).

Also known as: Placebo

Preseptal-pretarsal; Pretarsal-preseptal

Eligibility Criteria

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

You may qualify if:

• Patients over 18 years-of-age
• Clinical diagnosis eyelid dystonia, consisting of either blepharospasm or hemifacial spasm
• Patient wish to have treatment with botulinum toxin type A (BtA).

You may not qualify if:

• Patients unable to express their symptoms or history to the extent that they are not able to complete the study questionnaires, such as those suffering from dementia.
• Existence of potential contraindications to BtA treatment:
• Pregnancy
• Breastfeeding
• Prior allergic reaction
• Active infection or inflammation in the treatment area
• Neuromuscular and peripheral neuropathic disease
• Concomitant aminoglycoside therapy
• Patients with poor or unstable general health with activities of daily living severely affected by non-dystonia confounding factors, such as hospitalized or bed bound patients.

Sponsors & Collaborators

• The University of Hong Kong: lead
• Food and Health Bureau, Hong Kong: collaborator

Related Publications (23)

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  PMID: 3741202 BACKGROUND

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• Czyz CN, Burns JA, Petrie TP, Watkins JR, Cahill KV, Foster JA. Long-term botulinum toxin treatment of benign essential blepharospasm, hemifacial spasm, and Meige syndrome. Am J Ophthalmol. 2013 Jul;156(1):173-177.e2. doi: 10.1016/j.ajo.2013.02.001. Epub 2013 Mar 28.

  PMID: 23541393 BACKGROUND

• Harrison AR, Erickson JP, Anderson JS, Lee MS. Pain relief in patients receiving periocular botulinum toxin A. Ophthalmic Plast Reconstr Surg. 2008 Mar-Apr;24(2):113-6. doi: 10.1097/IOP.0b013e31816386e1.

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• Hilker R, Schischniaschvili M, Ghaemi M, Jacobs A, Rudolf J. Health related quality of life is improved by botulinum neurotoxin type A in long term treated patients with focal dystonia. J Neurol Neurosurg Psychiatry. 2001 Aug;71(2):193-9. doi: 10.1136/jnnp.71.2.193.

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• Muller J, Wissel J, Kemmler G, Voller B, Bodner T, Schneider A, Wenning GK, Poewe W. Craniocervical dystonia questionnaire (CDQ-24): development and validation of a disease-specific quality of life instrument. J Neurol Neurosurg Psychiatry. 2004 May;75(5):749-53. doi: 10.1136/jnnp.2003.013441.

  PMID: 15090572 BACKGROUND

• Hall TA, McGwin G Jr, Searcey K, Xie A, Hupp SL, Owsley C, Kline LB. Health-related quality of life and psychosocial characteristics of patients with benign essential blepharospasm. Arch Ophthalmol. 2006 Jan;124(1):116-9. doi: 10.1001/archopht.124.1.116.

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• Jankovic J, Schwartz K, Donovan DT. Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia, other focal dystonias and hemifacial spasm. J Neurol Neurosurg Psychiatry. 1990 Aug;53(8):633-9. doi: 10.1136/jnnp.53.8.633.

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  PMID: 14502050 BACKGROUND

• Costa J, Espirito-Santo C, Borges A, Ferreira JJ, Coelho M, Moore P, Sampaio C. Botulinum toxin type A therapy for blepharospasm. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD004900. doi: 10.1002/14651858.CD004900.pub2.

  PMID: 15674969 BACKGROUND

• Aramideh M, Ongerboer de Visser BW, Brans JW, Koelman JH, Speelman JD. Pretarsal application of botulinum toxin for treatment of blepharospasm. J Neurol Neurosurg Psychiatry. 1995 Sep;59(3):309-11. doi: 10.1136/jnnp.59.3.309.

  PMID: 7673963 BACKGROUND

• Jankovic J. Pretarsal injection of botulinum toxin for blepharospasm and apraxia of eyelid opening. J Neurol Neurosurg Psychiatry. 1996 Jun;60(6):704. doi: 10.1136/jnnp.60.6.704. No abstract available.

  PMID: 8648354 BACKGROUND

• Albanese A, Bentivoglio AR, Colosimo C, Galardi G, Maderna L, Tonali P. Pretarsal injections of botulinum toxin improve blepharospasm in previously unresponsive patients. J Neurol Neurosurg Psychiatry. 1996 Jun;60(6):693-4. doi: 10.1136/jnnp.60.6.693-a. No abstract available.

  PMID: 8648343 BACKGROUND

• Cakmur R, Ozturk V, Uzunel F, Donmez B, Idiman F. Comparison of preseptal and pretarsal injections of botulinum toxin in the treatment of blepharospasm and hemifacial spasm. J Neurol. 2002 Jan;249(1):64-8. doi: 10.1007/pl00007849.

  PMID: 11954870 BACKGROUND

• Albanese A, Sorbo FD, Comella C, Jinnah HA, Mink JW, Post B, Vidailhet M, Volkmann J, Warner TT, Leentjens AF, Martinez-Martin P, Stebbins GT, Goetz CG, Schrag A. Dystonia rating scales: critique and recommendations. Mov Disord. 2013 Jun 15;28(7):874-83. doi: 10.1002/mds.25579.

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• Wabbels B, Jost WH, Roggenkamper P. Difficulties with differentiating botulinum toxin treatment effects in essential blepharospasm. J Neural Transm (Vienna). 2011 Jun;118(6):925-43. doi: 10.1007/s00702-010-0546-9. Epub 2011 Jan 9.

  PMID: 21221669 BACKGROUND

• Wabbels B, Roggenkamper P. Botulinum toxin in hemifacial spasm: the challenge to assess the effect of treatment. J Neural Transm (Vienna). 2012 Aug;119(8):963-80. doi: 10.1007/s00702-011-0762-y. Epub 2012 Jan 10.

  PMID: 22231846 BACKGROUND

• Sarifakioglu N, Sarifakioglu E. Evaluating effects of preservative-containing saline solution on pain perception during botulinum toxin type-a injections at different locations: a prospective, single-blinded, randomized controlled trial. Aesthetic Plast Surg. 2005 Mar-Apr;29(2):113-5. doi: 10.1007/s00266-004-0062-0. Epub 2005 Apr 14.

  PMID: 15815811 BACKGROUND

• Jankovic J, Kenney C, Grafe S, Goertelmeyer R, Comes G. Relationship between various clinical outcome assessments in patients with blepharospasm. Mov Disord. 2009 Feb 15;24(3):407-13. doi: 10.1002/mds.22368.

  PMID: 19053054 BACKGROUND

• Marcet MM, Lemke BN, Greenwald MJ, Fountain TR, Roth S, Dubovy SR. Eyelid eversion for visualisation of the upper eyelid lamellae: an anatomical cadaver study. Br J Ophthalmol. 2011 Oct;95(10):1376-8. doi: 10.1136/bjophthalmol-2011-300020. Epub 2011 Jul 11.

  PMID: 21746734 BACKGROUND

• Marcet MM, Meyer DR, Greenwald MJ, Roth S, Selva D. Proximal tarsal attachments of the levator aponeurosis: implications for blepharoptosis repair. Ophthalmology. 2013 Sep;120(9):1924-9. doi: 10.1016/j.ophtha.2013.02.012. Epub 2013 Apr 16.

  PMID: 23601804 BACKGROUND

Related Links

• General information about eyelid spasms and treatment

MeSH Terms

Conditions

Blepharospasm; Hemifacial Spasm; Dystonia

Interventions

Pharmaceutical Preparations; Botulinum Toxins, Type A; Saline Solution; Injections

Condition Hierarchy (Ancestors)

Eyelid Diseases; Eye Diseases; Mouth Diseases; Stomatognathic Diseases; Spasm; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dyskinesias

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Crystalloid Solutions; Isotonic Solutions; Solutions; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Marcus M Marcet, MD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Honorary Clinical Assistant Professor

Study Record Dates

• First Submitted: March 18, 2018
• First Posted: April 26, 2018
• Study Start: July 1, 2015
• Primary Completion: October 31, 2017
• Study Completion: February 20, 2019
• Last Updated: April 26, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share