Neubotulinum Toxin Injection in Cerivical Dystonia

Study Overview
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Brief Summary
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24-Week Prospective, Double-Blinded, Randomized, Cross-over design in Multicenter Study of 50 unit of Neubotulinum Toxin Type A (Neuronox) and 100 unit of Neubotulinum Toxin Type A (Neuronox) injection for Cervical Dystonia in patient diagnosed with cervical dystonia 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 50 unit of Neubotulinum Toxin Type A (Neuronox) and 100 unit of Neubotulinum Toxin Type A (Neuronox) injection.

Detailed Description
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Three documented studies showed the clinical use of botulinum toxin for migraine prophylaxis.(26) Neubotulinum Toxin Type A, (Neu-BoNT/A), (Neuronox® ) (Medytox Inc, Ochang-eup, Cheongwon-gu, Cheongju-si, Chungcheongbuk-do, Republic of Korea), also known as Meditoxin in Korea, is a newly manufactured BoNT-A (Neu-BoNT/A) that was developed to provide features close to onabotulinum toxin A (5). Neuronox was tested in a murine model, and its effect on muscle force generation was equivalent to Botox® (ona-BoNT/A) (6). A previous multicenter randomized controlled trial showed that Neuronox and Botox® have equivalent efficacy and safety for the treatment of spastic equinus in children with cerebral palsy (6). However, 50 unit of Neubotulinum Toxin Type A (Neuronox) and 100 unit of Neubotulinum Toxin Type A (Neuronox) has not yet been investigated in cervical dystonia. This study is the extension of the NCT03805152

Official Title
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24-Week Prospective, Double-Blinded, Randomized, Cross-over Design in Multicenter Study of 50 Unit of Neubotulinum Toxin Type A (Neuronox) and 100 Unit of Neubotulinum Toxin Type A (Neuronox) Injection for Cervical Dystonia in Thai Patients

Conditions
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Cervical Dystonia

Intervention / Treatment
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* Drug: Neuronox ® Injection


Participation Criteria
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Eligibility Criteria
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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 18 - 100 years old. Subject diagnosed to be cervical dystonia. 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 TWSTRS, CDIP-58, SF36, and CES-D • during the whole study period 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, 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 TWSTRS, CDIP-58, 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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Crossover Assignment Double Blind randomized controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 unit of Neubotulinum Toxin Type A (Neuronox)<br>50 unit of Neubotulinum Toxin Type A (Neuronox) injection for Cervical Dystonia in patient diagnosed with cervical dystonia according to clinical diagnosis | Drug: Neuronox ® Injection<br>* Neuronox ® 50 or 100 unit intramuscular injection<br>* Other names: Neuronox ® 50 unit or 100 unit;|
| Experimental: 100 unit of Neubotulinum Toxin Type A (Neuronox)<br>100 unit of Neubotulinum Toxin Type A (Neuronox) injection for Cervical Dystonia in patient diagnosed with cervical dystonia according to clinical diagnosis | Drug: Neuronox ® Injection<br>* Neuronox ® 50 or 100 unit intramuscular injection<br>* Other names: Neuronox ® 50 unit or 100 unit;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toronto Western Spasmodic Torticollis Rating scale ( TWSTRS) | WSTRS ranged( 0-85 by summation of all 3 sub- scales ) higher represent a worse outcome TWSTRS Sub- scale includes TWSTRS-Total severity scale ( maximum 35 points) TWSTS-Disability scale (maximum 30 points) TWSTS-Pain scale (maximum 20 points) | 24 week | 
| Cervical Dystonia Impact Profile 58 ( CDIP-58) | Cervical Dystonia Impact Profile-58 items composed of 8 sub-scale Total score by summation of 8 subscale higher represent a worse outcome Analysis both total score (range 58-290 points) And sub-scale analysis composed of Head and neck symptoms ( 6 items ; 6-30 points) Pain and discomfort ( 5 items ; 5-25 points) Upper limb activity ( 9 items ; 9-45 points) Walking ( 9 items ; 9-45 points) Sleep ( 4 items ; 4-20 points) Annoyance ( 8 items ; 8-40 points) Mood (7 items ; 7-35 points) Psychosocial functioning ( 10 items ; 10-50 points) | 24 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparesion the quality of life 36 item ( SF 36) | Comparesion the quality of life (SF 36) pre- and post- 12 and 24 week ttreatment with 50 unit of Neubotulinum Toxin Type A (Neuronox) and 250 unit of Abobotulinum Toxin Type A (Dysport) this score has special formula calculation | 24 week | 
| Depression scale measured by Center of Epidemiologic Study of Depression 20 item ( CES-D 20) | Comparesion of CES-D pre- and post- 12 and 24 week treatment with 50 unit of Neubotulinum Toxin Type A (Neuronox) and 250 unit of Abobotulinum Toxin Type A (Dysport) Score ranged from 20-80 points higher represent a worse outcome | 24 week | 
| Depression scale measured by Patient Health Questionnaire Depression Scale (PHQ-9) | Comparesion of PHQ-9 pre- and post- 12 and 24 week treatment with 50 unit of Neubotulinum Toxin Type A (Neuronox) and 250 unit of Abobotulinum Toxin Type A (Dysport) There is the special scale calculation for diagnosis Major depressive disorder, Other depressive disorder and others,higher points /score represent a worse outcome ranged 0-27 points plus 3 points Total summation of 5-9 points indicate Minimal symptoms, 10-14 Minor depression ++ or Dysthymia* or Major depression, mild , 15-19 points Major depression, moderately severe ≥ 20 Major depression, severe (range PHQ 9 0-27 ) higher represent a worse outcome | 24 week | 
| Clinical Global Impression of Changed ( CGIC) | Comparesion of CGIC pre- and post- 12 and 24 week treatment with 50 unit of Neubotulinum Toxin Type A (Neuronox) and 250 unit of Abobotulinum Toxin Type A (Dysport) (range -3 to 3 points: -3,-2,-1,0,1,2,3) | 24 week |