Neubotulinum Toxin Injection in Cerivical Dystonia (NTCD)

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

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.

Study Overview

• Status: Completed
• Conditions: Cervical Dystonia
• Intervention / Treatment: Drug: Neuronox ® Injection

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 98 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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 50 unit of Neubotulinum Toxin Type A (Neuronox); 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; Neuronox ® 50 or 100 unit intramuscular injection; Other Names: Neuronox ® 50 unit or 100 unit
Experimental: 100 unit of Neubotulinum Toxin Type A (Neuronox); 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; Neuronox ® 50 or 100 unit intramuscular injection; Other Names: Neuronox ® 50 unit or 100 unit

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rajavithi Hospital

Publications and helpful links

General Publications

• Kongsaengdao S, Maneeton B, Maneeton N. Quality of life in cervical dystonia after treatment with botulinum toxin A: a 24-week prospective study. Neuropsychiatr Dis Treat. 2017 Jan 10;13:127-132. doi: 10.2147/NDT.S116325. eCollection 2017.
• Kongsaengdao S, Maneeton N, Maneeton B. Long-term quality of life in cervical dystonia after treatment with abobotulinum toxin A: a 2-year prospective study. Neuropsychiatr Dis Treat. 2018 Apr 26;14:1119-1124. doi: 10.2147/NDT.S152252. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2019
• Primary Completion (Actual): April 30, 2021
• Study Completion (Actual): May 30, 2021

Study Registration Dates

• First Submitted: October 5, 2020
• First Submitted That Met QC Criteria: October 9, 2020
• First Posted (Actual): October 12, 2020

Study Record Updates

• Last Update Posted (Actual): September 17, 2021
• Last Update Submitted That Met QC Criteria: September 16, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Dystonia; Dystonic Disorders; Torticollis; 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, Type A
• Other Study ID Numbers: A-02-2020

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