Ipratropium Bromide Spray as Treatment for Sialorrhea in Children

• ClinicalTrials.gov Identifier: NCT03747536
• Recruitment Status: Unknown
• First Posted: November 20, 2018
• Last Update Posted: November 21, 2018
• Sponsor: London Health Sciences Centre
• Information provided by (Responsible Party): Peng You, London Health Sciences Centre

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Sialorrhea	Drug: Ipratropium bromide; Other: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Study drug will be dispensed as a metered-dose spray bottle of ipratropium bromide or identical placebo prepared by the Hospital Pharmacy. Clinician, investigator, care provider, as well as outcome assessor will be blinded to the treatment.
• Primary Purpose: Treatment
• Official Title: Ipratropium Bromide Spray as Treatment for Sialorrhea in Children: a Randomized, Double-blind, Placebo-controlled Crossover Study
• Estimated Study Start Date: January 1, 2019
• Estimated Primary Completion Date: October 1, 2019
• Estimated Study Completion Date: January 1, 2021

Arms and Interventions

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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Change in Drooling Severity and Frequency Scale [ Time Frame: Change from baseline sialorrhea at 2 weeks following each treatment arm ]
   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.
2. Change in Drooling impact scale [ Time Frame: Change from baseline sialorrhea at 2 weeks following each treatment arm ]
   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.

Secondary Outcome Measures :

1. Patient Global Impression of Improvement Scale [ Time Frame: At start of trial and weekly self recording up to 8 weeks ]
   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
2. Adverse effect [ Time Frame: Intermittent up to 8 weeks ]
   Documentation of all adverse effects encountered during study period
3. Patient feedback [ Time Frame: Weekly self recording up to 8 weeks. ]
   Open ended patient comment related to the intervention. To be collected through patient booklet

Eligibility Criteria

• Ages Eligible for Study: 5 Years to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Julie Strychowsky, MD; 519 685 8500 ext 58242; julie.strychowsky@lhsc.on.ca

Contact: Agnieszka Dzioba, PhD; Agnieszka.Dzioba@lhsc.on.ca

Sponsors and Collaborators

London Health Sciences Centre

Investigators

• Principal Investigator: Julie Strychowsky, MD; London Health Science Centre

More Information

• Responsible Party: Peng You, Principle Investigator, Department of Otolaryngology Head and Neck Surgery, Western University, London Health Sciences Centre
• ClinicalTrials.gov Identifier: NCT03747536
• Other Study ID Numbers: LondonHSC
• First Posted: November 20, 2018
• Last Update Posted: November 21, 2018
• Last Verified: November 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Peng You, London Health Sciences Centre:

Ipratropium bromide; Sialorrhea; Pediatric

Additional relevant MeSH terms:

Sialorrhea; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Bromides; Ipratropium; Anticonvulsants; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Cholinergic Antagonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action