Study of Abobotulinum Toxin Versus Neubotulinum Toxin Injection For Hemifacial Spasm in Thai Patients (DNHFS)

A 48-Week Prospective, Double-Blinded, Randomized, Cross-over Design in Multicenter Study of 100 Unit of Abobotulinum Toxin Type A (Dyspor) Versus 33.33 Unit of Neubotulinum Toxin Type A (Neuronox) Injection For Hemifacial Spasm in Thai Patients

A 48-Week Prospective, Double-Blinded, Randomized, Cross-over design in Multicenter Study of, 100 unit of Abobotulinum Toxin Type A (Dysport) and 33.33 unit of Neubotulinum Toxin Type A (Neuronox) injection for Hemifacial Spasm in patient diagnosed with Hemifacial Spasm according to clinical diagnosis. It was designed to evaluate the efficacy, safety, tolerability, quality of life and the comparesion the improvement after treatment by of Abobotulinum Toxin Type A (Dysport) injection versus Neubotulinum Toxin Type A (Neuronox) Injection.

Study Overview

• Status: Not yet recruiting
• Conditions: Hemifacial Spasm
• Intervention / Treatment: Drug: Injection botulinum toxin A ( Dysport 100 unit or Neuronox 33.33 unit)

Detailed Description

The primary objective of the study was to evaluate the safety and efficacy of Abobotulinum Toxin Type A (Dysport) injection and Neubotulinum Toxin Type A (Neuronox) Injection for Hemifacial Spasm. The secondary objective of the study was to evaluate the quality of life of Abobotulinum Toxin Type A (Dysport) and Neubotulinum Toxin Type A (Neuronox) Injection for Hemifacial Spasm.

120 patients diagnosed with Hemifacial Spasm were planned to be enrolled into the study. Total of 120 patients planed to be and randomized.

Efficacy criteria:

Primary efficacy variable: Comparesion of pre- and post- treatment after 12 and 24 week scale with 33.33 unit of Neubotulinum Toxin Type A (Neuronox) and 100 unit of Abobotulinum Toxin Type A (Dysport); as following

1. 24 hours HFS diary record for 12 week after treatment Time to peak improvement, response duration period, Total intensity score per day, duration of facial muscle spasm (hour per day) and duration of functional impairment (hour per day) record for 12 week after each treatment will be assessed
2. Hemifacial Spasm- 30 Questionnaire (Thai version). Seven subscales (30 items). Mobility (5 items), activity of daily living (5 items) and communication (3 items) are classified as physical health domain. Emotional well-being (7 items), stigma (4 items), social support (3 items) and cognition (3 items) are classified as mental health domain
3. Abnormal involuntary movement scale (AIMS) (Thai version) Rating sacle of the severity of movements in 7 regions, each on a 5 points scale and a separate rating of the overall severity of the abnormal movements, judged on the amplitude of movements, incapacitation postures and positions, including sitting in chair, opening the mouth, tapping the thumb against each finger, holding the hand out stretched and standing and walking, are included. Dental status is also rated, as the presence or absence of problems with teeth or dentures.

Secondary efficacy variables: : Comparesion of pre- and post- treatment after 12 and 24 week scale with 50 unit of Neubotulinum Toxin Type A (Neuronox) and 250 unit of Abobotulinum Toxin Type A (Dysport); as following

1. 36-item questionnaire and comprises eight domains: Physical functioning (PF), Role limitations due to physical health (RP), Role limitations due to emotional problems(RE), Vitality (VT), Mental health (MH), Social functioning (SF), Bodily pain (BP), General health (GH)
2. Center of Epidemiologic study -Depression scale (CES-D)
3. Patient health Questionnaire - 9 item (PHQ-9)
4. The investigator's /patient's global assessment of change (GAC) Safety criteria: The assessment of safety and tolerability were based mainly on the frequency of adverse events.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: subsai kongsaengdao, M.D.; Phone Number: +66818180890; Email: skhongsa@gmail.com
• Study Contact Backup: Name: Arkhom arayawichanon, M.D.; Phone Number: +66816653741; Email: aarayawi@gmail.com

Study Locations

• Thailand
  • Bangkok, Thailand, 10400
    • Rajavithi Hospital
  • Lampang, Thailand, 52000
    • Lampang Hospital
  • Surat Thani, Thailand, 84000
    • Surat Thani Hospital
  • Ubon Ratchathani, Thailand, 34000
    • Sappasitthiprasong Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The subject has to grant permission to enter into the study by signing and dating the informed consent form before completing any study-related procedure such as any assessment or evaluation not related to the normal medical care of the subject.
• Able to give written inform consent and retained one copy of the consent form
• Male or female subject, aged between 20 - 100 years old.
• Subject diagnosed to be hemifacial spasm.
• Female subject in good health and sexually active was instructed by the investigator to avoid pregnancy during the study and to use condom or other contraceptive measure if necessary. The subject was required to have a negative urine pregnancy test before being eligible for the study. (At each of the subsequent visit, a urine pregnancy test was performed).
• Subject judged to be reliable for compliance for taking medication and capable of recording the effects of the medication and motivated in receiving benefits from the treatment.

Subject should undergo a normal physical and neurological examination HFS 30, AIMS, SF36, and CES-D, PHQ 9 , and patient diary

Exclusion Criteria:

• The subject was pregnant or lactating.
• The subject was a female at risk of pregnancy during the study and not taking adequate precautions against pregnancy.
• The subject had a known hypersensitivity to any of the test materials or related compounds.
• The subject was unable or unwilling to comply fully with the protocol.
• The subject received any unlicensed drug within the previous 6 months.
• Treatment with investigational drug (s) within 6 months before the screening visit.
• The subject had previously entered in this study.
• Subject with past history of botulism, other neuromuscular disorder (e.g. myasthenia gravis, Lambert - Elton Syndrome)
• Subject with significant medical / neurological / psychiatric disorders such as blood dyscrasia, thrombocytopenia, INR>1.2 rheumatoid arthritis, congestive heart failure, coronary artery heart diseases, dementia, psychosis, or other conditions which could influence the clinical trial.
• Known history of drug abuse (narcotic (s), cafergot, or others) or drug (botulinum toxin type A) allergy.
• Unable to cooperate fill-up HFS 30, AIMS, SF36, and CES-D
• Patient who planned to schedule elective surgery during the study.
• The used of aminoglycoside antibiotics and curare were not allowed during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: abobotulinum toxin A; Abobotulinum Toxin Type A (Dysport) dose was investigated: dose: 100 units ( various units each site depend on clinical )	Drug: Injection botulinum toxin A ( Dysport 100 unit or Neuronox 33.33 unit); injection of toxin on facial muscle
EXPERIMENTAL: neubotulinum toxin A; Neubotulinum Toxin Type A (Neuronox) dose was investigated: dose: 33.33 units ( various units each site depend on clinical )	Drug: Injection botulinum toxin A ( Dysport 100 unit or Neuronox 33.33 unit); injection of toxin on facial muscle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to peak improvement	day of latency to treatment peak effectiveness	12 weeks
response duration period	day of duration to treatment peak effectiveness	12 weeks
Total intensity score per day	severity and duration calculated score from patient diary range between 0-6048 higher score mean worse	12 weeks
duration of facial muscle spasm	duration calculated score from patient diary outcome measure as hour per 12 week	12 weeks
duration of functional impairment	duration of functional impairment calculated score from patient diary outcome measure as hour per 12 week	12 weeks
Hemifacial Spasm- 30	Seven subscales (30 items). Mobility (5 items), activity of daily living (5 items) and communication (3 items) are classified as physical health domain. Emotional well-being (7 items), stigma (4 items), social support (3 items) and cognition (3 items) are classified as mental health domain higher score represent worse ( range from 0-120 higher score represent worse)	12 weeks
Abnormal involuntary movement scale (AIMS)	Rating sacle of the severity of movements in 7 regions, each on a 5 points scale and a separate rating of the overall severity of the abnormal movements, judged on the amplitude of movements, incapacitation postures and positions, including sitting in chair, opening the mouth, tapping the thumb against each finger, holding the hand out stretched and standing and walking, are included. Dental status is also rated, as the presence or absence of problems with teeth or dentures	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
36-item questionnaire	36-item questionnaire and comprises eight domains: Physical functioning (PF), Role limitations due to physical health (RP), Role limitations due to emotional problems(RE), Vitality (VT), Mental health (MH), Social functioning (SF), Bodily pain (BP), General health (GH) Special calculation of this scale are specified	12 weeks
Center of Epidemiologic study -Depression scale (CES-D)	20 item depressive screening scale ( range 0-80 higher score represent worse)	12 weeks
Patient health Questionnaire - 9 item (PHQ-9)	9 item depressive screening scale range between 0-27 higher score represent worse	12 weeks
The investigator's /patient's global assessment of change	5 scale evaluate clinical status range from -3 to 3 higher score represent good outcome	12 weeks

Collaborators and Investigators

• Sponsor: Rajavithi Hospital

Publications and helpful links

General Publications

• Kongsengdao S, Kritalukkul S. Quality of life in hemifacial spasm patient after treatment with botulinum toxin A; a 24-week, double-blind, randomized, cross-over comparison of Dysport and Neuronox study. J Med Assoc Thai. 2012 Mar;95 Suppl 3:S48-54.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 1, 2023
• Primary Completion (ANTICIPATED): March 1, 2024
• Study Completion (ANTICIPATED): April 1, 2024

Study Registration Dates

• First Submitted: October 4, 2020
• First Submitted That Met QC Criteria: October 9, 2020
• First Posted (ACTUAL): October 19, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 6, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Stomatognathic Diseases; Mouth Diseases; Neuromuscular Manifestations; Spasm; Hemifacial Spasm; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: STUDY NO. A-01-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No