A 48-Week Prospective, Double-Blinded, Randomized, Cross-over Design in Multicenter Study of 250 Unit of Dysport Versus 50 Unit of Neuronox Injection For Cervical Dystonia in Thai Patients

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.