Abobotulinum Toxin and Neubotulinum Toxin Injection in Cerivical Dystonia
Condition: Cervical Dystonia
MeSH terms: Dystonia; Dystonic Disorders; Torticollis
Study type: Interventional
Phase: Phase 3

Summary: 
      A 48-Week Prospective, Double-Blinded, Randomized, Cross-over design in Multicenter Study of,
      250 unit of Abobotulinum Toxin Type A (Dysport) and 50 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
      Abobotulinum Toxin Type A (Dysport) injection versus Neubotulinum Toxin Type A
      (Neuronox)Injection.
    

Detailed description: 
      Abobotulinum neurotoxin type A, abo-BoNT/A, (Dysport®) is the most potent biological toxin
      produced from Clostridium botulinum. In 1920, Dr Hermann Sommer of the Hooper Foundation at
      the University of California made the first attempt to purify the botulinum toxin. His work
      paved the way for further studies at Cam (Fort) Detrick on botulinum toxin type B, C, D, and
      E, particularly during the World War II. In 1946, Dr Carl Lammanna first crystalised the
      botulinum toxin type A and found it was composed of toxic units bound to non-toxic unit
      proteins. Dr Vernon Brooks, suggested that the botulinum toxin type A might be use to reduce
      the activity of hyperactive muscle in 1950s (9). In 1970-1971 Dr Alan B. Scott evolved an
      elegant electrophysiology EMG-guided technique to inject small doses of various agents to
      produce weakening of extraocular muscle for non-surgical treatment of strabismus. By 1973, he
      demonstrated in animal experiments that botulinum can be used for the treatment of strabismus
      and suggested that it might be of benefit for treating blepharospasm. In 1977, the U.S.FDA
      approved the botulinum toxin for human study and the result of the first clinical trial of
      botulinum toxin for strabismus was published in 1980. The U.S. FDA approved the botulinum
      toxin treatment in various movement disorders in 1990.

      In 1991, the United Kingdom authorized the licence of Dysport®, and was commercially marketed
      by Speywood Pharmacuticals Ltd (previously Porton Products Ltd). After it's initial success
      in the treatment of strabismus, Botulinum toxin was used to treat other ophthalmological
      conditions, such as dysthyroid ophthalmopathy (1) and nystagmus (2) blepharospasm (3), focal
      abnormal movement such as hemifacial spasm, spasmodic torticollis, spasticity such as
      dystonia and pain such as cervical and lumbar pain (4).

      There has been a steady stream of ideas for other uses, such as urinary, rectal,
      gastroesophageal sphincter and sphincter of Oddi disturbances, cosmetic (reduction of
      wrinkle) and eventually tension-type headache. In the past few years, some clinical
      observation from Brin, MasKop reported that patients who had been injected with botulinum
      toxin for wrinkle had some benefit for relieving headache. 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, Neuronox has not yet been
      investigated in post-stroke upper limb spasticity and cervical dystonia.

      STUDYOBJECTIVES Primary Objective Comparesion of pre- and post- treatment after 12 and 24
      week TWSTRS and CDIP-58 scale with 50 unit of Neubotulinum Toxin Type A (Neuronox) and 250
      unit of Abobotulinum Toxin Type A (Dysport) incervical dystonia patients 8.2 Secondary
      Objective Comparesion the quality of life (SF 36, 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) incervical dystonia patients There were two treatment arms in
      crossover designed study and the interest was only on the comparison of each pre- and post-
      treatment outcomes of (Dysport)and (Neuronox) , two pair- wise comparisons pre and post
      treatment after 12 and 24 week scale were carried out. For each of the pair-wise comparison,
      2-sided p-value was used to ensure that the overall Type I error=0.05. Beta error 80%
      Multiple repeated analysis and general linear model will be analysed in the efficacy of
      treatment.Two-sided exact p-values were reported in the efficacy analyses. Demographic and
      safety analyses were based on the summary of descriptive statistics.

      At the screening visit and prior to performance of any study procedures, the investigators
      would explain the details of the study and the subject would have to sign on the written
      informed consent, exclusion criteria, and inclusion criteria Each subject who was willing to
      enrol into the study was asked about their medical history as well as their recent and
      current medications being taken.

      All enrolled subjects were asked to undertake an initial physical examination and had to
      satisfy the criteria for the inclusion /exclusion before being enrolled into the study.

      All patients were asked to complete physical examination, TWSTRS, CDIP-58, SF36, PHQ9 and
      CES-D .

      Laboratory blood (livers tests, haematology,) examinations, urine pregnancy test) were
      performed for safety reasons.

      1Inclusion Criteria The subjects need to satisfy the following criteria before being allowed
      to participate in the study:

        -  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 at will. 9.2.2 Exclusion Criteria The subject WERE NOT
           ALLOWED TO enter/continue into the study, if :.

        -  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.
    

Intervention name(s): Neuronox(R); Dysport (R)
Intervention type(s): Drug; Drug
Intervention description(s): Injection botulinum toxin intramuscular for affected neck muscle; Intramuscular injection
Other intervention name(s): Intramuscular injection
Intervention MeSH terms: abobotulinumtoxinA; Botulinum Toxins, Type A
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Double Blind randomized controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment