Botulinum Toxin-A for Sialorrhoea Treatment in Asian Adults With Neurological Diseases

Sponsor

University of Malaya (Other)

Overall Status

Completed

CT.gov ID

NCT02425176

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The efficacy of Botulinum toxin A (BoNT-A) in Asian population has not been properly studied and there is no literature available on the most efficacious dose of BoNT-A for sialorrhoea treatment. This research is aimed to find the dose of Dysport® that would be efficacious without treatment-related adverse events and the duration of effectiveness of the drug for sialorrhea treatment in Malaysian patients. The efficacy, safety, tolerability and adverse effects of three doses of Dysport®(50MU, 100MU and 200MU) are examined at 2,6,12 and 24 weeks post injection in this double-blinding, randomized trial.

Condition or Disease	Intervention/Treatment	Phase
Sialorrhea	Drug: Botulinum toxin A (BoNT-A) 50U Drug: Botulinum toxin A (BoNT-A) 100U Drug: Botulinum toxin A (BoNT-A) 200U	Phase 2/Phase 3

Detailed Description

Study Objectives:

To determine the efficacy, safety, tolerability and adverse effects of three doses of Dysport® (50MU, 100MU and 200MU) in the treatment of sialorrhoea in Asian patients with neurological disorders/diseases and to determine the most efficacious dose.

Study design:

Dose-ranging double blind pilot study.

Sample size:

At least 30 adult patients with various neurological disorders complicated with sialorrhoea including stroke, motor neurone disease, traumatic brain injury and Parkinsonism would be divided into 3 dosing groups.

Study method:

Patients who satisfy inclusion criteria and have given informed consent would be randomized into 3 equal groups given different total doses-50MU, 100MU, 200MU. The total dose will be divided equally and give to each of 4 salivary glands viz. the submandibular and parotid gland bilaterally. For example, if 200MU is to be given in total, 50MU would be given to each gland. Injections would be given via a 25G needle to each gland with ultrasound guidance for better needle placement. One site will be injected per gland.

Primary outcome measure The percentage reduction in the rate of saliva production (as measured by difference in mean weight of dental rolls per minute from baseline) for each of the groups given different doses of Dysport® at 2,6,12 and 24 weeks post injection.

Secondary outcome measure

Patient's subjective assessment of improvement in sialorrhoea using the Drooling Frequency and Severity Scale (Thomas-Stonell scale) at 2,6,12 and 24 weeks post-injection.
Duration to maximum reduction in salivation (as measured by the maximum reduction in weight of dental rolls)

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Double-blind Randomised Controlled Trial Investigating the Most Efficacious Dose of Botulinum Toxin-A for Sialorrhoea Treatment in Asian Adults With Neurological Diseases

Study Start Date :

Sep 1, 2009

Actual Primary Completion Date :

Feb 1, 2014

Actual Study Completion Date :

Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Botulinum toxin A (BoNT-A) 50U Drug dilution and dosage: Prepare a mother solution of 500 U/ml by diluting Botulinum toxin A Dysport® with 1 ml of 0.9% saline. Prepare in 1 ml syringe to get 50U/ml :0.1 ml drawn from the mother solution and add 0.9 ml of 0,9% saline. Total volume of 1 ml. Intervention: Botulinum toxin A (BTX-A) 50U are divided equally into 4 salivary glands, 12.5U each gland	Drug: Botulinum toxin A (BoNT-A) 50U Drug intervention: The total dose is divided equally and injected into 4 salivary glands (submandibular and parotid gland bilaterally) via a 25G or 23G needle with ultrasound guidance. One site is injected per gland. Drug is only injected once at baseline Other Names: Dysport
Active Comparator: Botulinum toxin A (BoNT-A) 100U Drug dilution and dosage: 1. Prepare a mother solution of 500 U/ml by diluting Botulinum toxin A Dysport® with 1 ml of 0.9% saline. 2. Prepare in 1 ml syringe to get 100U/ml :0.2 ml drawn from the mother solution and add 0.8 ml of 0.9% saline. Total volume of 1 ml. Intervention: Botulinum toxin A (BTX-A) 100U are divided equally into 4 salivary glands, 25U each gland	Drug: Botulinum toxin A (BoNT-A) 100U The total dose is divided equally and injected into 4 salivary glands (submandibular and parotid gland bilaterally) via a 25G or 23G needle with ultrasound guidance. One site is injected per gland. Other Names: Dysport
Active Comparator: Botulinum toxina A (BoNT-A) 200U Drug dilution and dosage: 1. Prepare a mother solution of 500 U/ml by diluting Botulinum ToxinA Dysport® with 1 ml of 0.9% saline. 2. Prepare in 1 ml syringe to get 200U/ml :0.4 ml is drawn from the mother solution and 0.6ml of 0.9% saline is added. Total volume of 1 ml. Intervention: Botulinum toxin A (BTX-A) 200U are divided equally into 4 salivary glands, 50U each gland	Drug: Botulinum toxin A (BoNT-A) 200U The total dose is divided equally and injected into 4 salivary glands (submandibular and parotid gland bilaterally) via a 25G or 23G needle with ultrasound guidance. One site is injected per gland. Other Names: Dysport

Arm

Intervention/Treatment

Active Comparator: Botulinum toxin A (BoNT-A) 50U

Drug dilution and dosage: Prepare a mother solution of 500 U/ml by diluting Botulinum toxin A Dysport® with 1 ml of 0.9% saline. Prepare in 1 ml syringe to get 50U/ml :0.1 ml drawn from the mother solution and add 0.9 ml of 0,9% saline. Total volume of 1 ml. Intervention: Botulinum toxin A (BTX-A) 50U are divided equally into 4 salivary glands, 12.5U each gland

Drug: Botulinum toxin A (BoNT-A) 50U

Drug intervention: The total dose is divided equally and injected into 4 salivary glands (submandibular and parotid gland bilaterally) via a 25G or 23G needle with ultrasound guidance. One site is injected per gland. Drug is only injected once at baseline

Other Names:

Dysport

Active Comparator: Botulinum toxin A (BoNT-A) 100U

Drug dilution and dosage: 1. Prepare a mother solution of 500 U/ml by diluting Botulinum toxin A Dysport® with 1 ml of 0.9% saline. 2. Prepare in 1 ml syringe to get 100U/ml :0.2 ml drawn from the mother solution and add 0.8 ml of 0.9% saline. Total volume of 1 ml. Intervention: Botulinum toxin A (BTX-A) 100U are divided equally into 4 salivary glands, 25U each gland

Drug: Botulinum toxin A (BoNT-A) 100U

The total dose is divided equally and injected into 4 salivary glands (submandibular and parotid gland bilaterally) via a 25G or 23G needle with ultrasound guidance. One site is injected per gland.

Other Names:

Dysport

Active Comparator: Botulinum toxina A (BoNT-A) 200U

Drug dilution and dosage: 1. Prepare a mother solution of 500 U/ml by diluting Botulinum ToxinA Dysport® with 1 ml of 0.9% saline. 2. Prepare in 1 ml syringe to get 200U/ml :0.4 ml is drawn from the mother solution and 0.6ml of 0.9% saline is added. Total volume of 1 ml. Intervention: Botulinum toxin A (BTX-A) 200U are divided equally into 4 salivary glands, 50U each gland

Drug: Botulinum toxin A (BoNT-A) 200U

The total dose is divided equally and injected into 4 salivary glands (submandibular and parotid gland bilaterally) via a 25G or 23G needle with ultrasound guidance. One site is injected per gland.

Other Names:

Dysport

Outcome Measures

Primary Outcome Measures

Change from baseline in the amount of saliva produced within 6 months [2,6,12 and 24 weeks post injection]
the amount of saliva produced was measured by the differential weight of a dental roll gauze placed in the buccal mucosal cavity calculated via an electronic microbalance scale to the nearest 0.0001 g

Secondary Outcome Measures

subjective report of sialorrhea/ drooling within 6 months post injection [2,6,12 and 24 weeks post injection]
subjective report of sialorrhea using the Drooling Frequency and Severity Scale (DFS).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients ≥ 18 years old.
Patients with neurological disorder including stroke, motor neurone disease, traumatic brain injury and Parkinsonism, diagnosis confirmed clinically by their treating physicians.
Patients with a Thomas-Stonell Drooling Frequency and Severity Scale combined drooling ranking of ≥5.
Patients who are able to give signed informed consent and are willing and able to comply with scheduled visits, treatment plan and other study procedure.