Ipratropium Bromide Spray as Treatment for Sialorrhea in Children

Ipratropium Bromide Spray as Treatment for Sialorrhea in Children: a Randomized, Double-blind, Placebo-controlled Crossover Study

Double-blind, clinical trial investigating the effects of ipratropium spray versus placebo spray in children with sialorrhea

Study Overview

• Status: Unknown
• Conditions: Sialorrhea
• Intervention / Treatment: Drug: Ipratropium bromide; Other: Placebo

Detailed Description

Excess drooling, or sialorrhea, is a chronic problem seen in pediatric patients with oral-motor dysfunction or neurodevelopmental abnormalities. Despite significant social and physical detriment from sialorrhea, an effective and safe treatment remains elusive.

The investigator's objective is to study the effect of sublingual ipratropium (an anticholinergic aerosol spray) on sialorrhea in the pediatric population

Method: A double-blind, randomized, placebo-controlled cross-over trial of sublingual ipratropium bromide application in pediatric patients with inappropriate drooling. Patients are recruited from the sialorrhea clinic and informed consent is obtained. Patients are randomized to receive ipratropium bromide, 1- 2 metered doses (sprays) of active drug (21 micrograms per metered dose) or matching placebo, every 6 hours up to a maximum of 4 times per day, in a double-blind, cross-over design using randomization tables. Total treatment length is two weeks for each limb of the study with a 2 week washout period. The primary outcome measure is the reporting of sialorrhea using a validated scales. Secondary outcome includes global assessment of treatment, patient satisfaction, and adverse effects.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Julie Strychowsky, MD; Phone Number: 58242 519 685 8500; Email: julie.strychowsky@lhsc.on.ca
• Study Contact Backup: Name: Agnieszka Dzioba, PhD; Email: Agnieszka.Dzioba@lhsc.on.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children and adolescents aged 5-18 with a history of excessive drooling

Exclusion Criteria:

• known hypersensitivity to ipratropium bromide
• surgery for sialorrhea within one year
• the concurrent use of acetylcholinesterase inhibitors, cholinergic agents, or anticholinergic agents
• botulinum toxin for drooling within the preceding six months
• a history of glaucoma
• the presence of clinically significant urinary retention or outflow obstruction as evidenced by patient history or documented urodynamic studies

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: Intervention; ipratropium bromide administered via metered dose spray (21 micrograms per spray). 1-2 spray sublingual or to buccal mucosa every 6 hours up to 4 times a day	Drug: Ipratropium bromide; ipratropium bromide via metered dose spray (21 micrograms per spray); Other Names: Atrovent
Placebo Comparator: Placebo; normal saline administered via metered dose spray. 1-2 spray sublingual or to buccal mucosa every 6 hours up to 4 times a day	Other: Placebo; normal saline delivered via metered dose spray

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Drooling Severity and Frequency Scale	Also referred to as the Thomas Stonell and Greenberg scale. This is a validated tool using patient reported scores for drooling severity and frequency. Drooling severity is scored on a scale with minimum value of 1 and maximum value of 5. A higher value represents a worse outcome. The frequency is scored on a scale with minimum value of 1 and maximum value of 4. A higher value represents a worse outcome. The subscales (severity and frequency) can be interpreted independently or combined through addition to compute a total score.	Change from baseline sialorrhea at 2 weeks following each treatment arm
Change in Drooling impact scale	The drooling impact scale is a validated self-administered questionnaire used to measure saliva-control in children. The scale consists of 10 questions/subscales, each with a minimum score of 1 and a maximum score of 10. For all subscales, the higher value represents a worse outcome. The total score is reported and is calculated by adding the score of all 10 subscales.	Change from baseline sialorrhea at 2 weeks following each treatment arm

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Global Impression of Improvement Scale	The Patient Global Impression of improvement scale is a single 7-point scale that requires the patient/caregiver to assess how much the illness has improved or worsened relative to a baseline state at the beginning of the intervention. The minimum score is 1 and the maximum score is 7. A higher value represents a worse outcome. To be collected through patient booklet	At start of trial and weekly self recording up to 8 weeks
Adverse effect	Documentation of all adverse effects encountered during study period	Intermittent up to 8 weeks
Patient feedback	Open ended patient comment related to the intervention. To be collected through patient booklet	Weekly self recording up to 8 weeks.

Collaborators and Investigators

• Sponsor: London Health Sciences Centre
• Investigators: Principal Investigator: Julie Strychowsky, MD, London Health Science Centre

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2019
• Primary Completion (Anticipated): October 1, 2019
• Study Completion (Anticipated): January 1, 2021

Study Registration Dates

• First Submitted: November 14, 2018
• First Submitted That Met QC Criteria: November 19, 2018
• First Posted (Actual): November 20, 2018

Study Record Updates

• Last Update Posted (Actual): November 21, 2018
• Last Update Submitted That Met QC Criteria: November 19, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Pediatric; Sialorrhea; Ipratropium bromide
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Mouth Diseases; Salivary Gland Diseases; Sialorrhea; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Bromides; Ipratropium
• Other Study ID Numbers: LondonHSC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No