Xerostomia in Patients With a Life-limiting Condition or Frailty

Xerostomia in Patients With a Life-limiting Condition or Frailty: a Double-blind Placebo-controlled Randomized Clinical Trial

Xerostomia, the subjective feeling of dry mouth, is a common symptom during the last year of life in patients with a life-limiting condition or frailty. Xerostomia leads to functional alterations (such as burning sensations, an altered taste perception, and difficulties with chewing, swallowing, and speaking), has disabling social consequences and significantly downgrades the perceived quality of life. It is an under-exposed and under-treated symptom often caused by alterations in the quality and quantity of saliva.

Locally administered pilocarpine could be a promising drug in this regard as it alleviates xerostomia by increasing the production of saliva.

Study Overview

• Status: Not yet recruiting
• Conditions: Xerostomia; Dry Mouth
• Intervention / Treatment: Drug: Pilocarpine; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Marieke van den Beuken- van Everdingen, Prof.; Phone Number: 0031(0)43 3877392; Email: m.vanden.beuken@mumc.nl
• Study Contact Backup: Name: Evelien Neis, Dr.; Phone Number: 0031(0)43 3875610; Email: evelien.neis@mumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• have a life-limiting condition or frailty
• have the complaint dry mouth ≥ 5 on an 11 point numerical rating scale (ranging from 0= no dry mouth to 10= worst dry mouth ever)
• fulfil the single SQ 'Would I be surprised if my patient dies within the year? (no)

Exclusion Criteria:

• their life expectancy is less than 4 weeks (the primary endpoint at 4 weeks)
• they have had radiotherapy to the salivary glands or suffer from Sjögrens disease (impact on dry mouth)
• cognitively impaired to such an extent that there is insufficient understanding to complete questionnaires

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; study whether topical pilocarpine drops induce a clinically significant improvement in xerostomia
Experimental: Treatment	Drug: Pilocarpine; study whether topical pilocarpine drops induce a clinically significant improvement in xerostomia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentage responders at week 4 of topical pilocarpine administration, as compared to baseline.	A patient counts as a responder with, at least, a 2-point reduction on the 11-point NRS	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean difference in NRS dry mouth scores in the pilocarpine group at all time-points, as compared to the placebo group	Mean difference in NRS dry mouth scores is determined as mean change from baseline	4 - 12 weeks
Change in Oral Health-Related Quality of Life (OHRQoL) upon pilocarpine treatment, as compared to the placebo group	The OHRQoL is measured using the Geriatric Oral Health Assessment Index (GOHAI-NL)	4 - 12 weeks
Change in the Health-Related Quality of Life upon pilocarpine treatment, as compared to the placebo group	The HRQoL will be assessed using the EQ-5D-5L questionnaire	4 - 12 weeks
Change in clinical functioning upon pilocarpine treatment, as compared to the placebo group	Clinical functioning is determined using the Patient-reported functional status (PRFS) questionnaire	4 - 12 weeks
Change in the Global Perceived Effect (GPE) upon pilocarpine treatment, as compared to the placebo group	The GPE is determined by a globally experienced effect score	4 - 12 weeks
The durability of the effect of the use of pilocarpine on xerostomia	The durability will be displayed in percentage	4 - 12 weeks
The adherence rate of patients	Adherence will be displayed in percentage	4 -12 weeks
Possible side effects related to the intake of pilocarpine medication, as compared to the placebo group	Side effects are made transparent by providing an overview of which and how many side effects occur	4 - 12 weeks
Cost Effectiveness Analysis (CEA) of the pilocarpine treatment	The costst of patients is analysed using the medical consumption questionnaire (iMCQ)	4 - 12 weeks

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development
• Investigators: Principal Investigator: Marieke van den Beuken- van Everdingen, Prof., Maastricht University and/or Maastricht UMC+

Publications and helpful links

General Publications

• Theunissen M, Rideaux-Seferina S, Magdelijns FJ, Janssen DJA, van den Beuken-van Everdingen MHJ. Local Oral Pilocarpine Drops for Relieving Xerostomia (Dry Mouth) in the Elderly: A Pilot Study. J Am Med Dir Assoc. 2021 Jan;22(1):185-186. doi: 10.1016/j.jamda.2020.06.036. Epub 2020 Aug 13. No abstract available.

Helpful Links

• ZonMW Programma Palliantie

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): February 1, 2025
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: August 16, 2022
• First Submitted That Met QC Criteria: August 16, 2022
• First Posted (Actual): August 18, 2022

Study Record Updates

• Last Update Posted (Actual): August 18, 2022
• Last Update Submitted That Met QC Criteria: August 16, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Xerostomia; Dry mouth; Pilocarpine
• Additional Relevant MeSH Terms: Pathologic Processes; Stomatognathic Diseases; Mouth Diseases; Salivary Gland Diseases; Frailty; Xerostomia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Cholinergic Agonists; Miotics; Muscarinic Agonists; Pilocarpine
• Other Study ID Numbers: 2022-501084-41-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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