Study of Glycopyrrolate for Moderate-to-severe Sialorrhea in Parkinson's Disease (GLYCOPAR)

A Randomized, Placebo-controlled, 2-arm Parallel-group Superiority Phase II Study of GLYCOpyrrolate for Moderate-to-severe Sialorrhea in PARkinson's Disease

Sialorrhea is a frequently occurring problem with detrimental effect on quality of life in 25% of PD patients. Currently, there is no intervention approved for sialorrhea in Parkinsons and evidence is only available for a 30-day effect or less. We hypothesize that glycopyrrolate will have a lasting effect in the reduction of sialorrhea in PD patients.

Study Overview

• Status: Unknown
• Conditions: Parkinson's Disease; Sialorrhea
• Intervention / Treatment: Drug: Placebo; Drug: Glycopyrrolate

Detailed Description

To assses if Glycopyrrolate has a long lasting effect on sialorrhea for patients with Parkinsons.

• Study Type: Interventional
• Enrollment (Anticipated): 28
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shawna Reddie; Phone Number: 19369 613-798-5555; Email: sreddie@ohri.ca
• Study Contact Backup: Name: Tiago Mestre, MSc, MD; Phone Number: 18986 613-798-5555; Email: tmestre@toh.ca

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Recruiting
      • The Ottawa Hospital - Civic Campus
      • Contact: Shawna Reddie; Phone Number: 19369 613-798-5555; Email: sreddie@ohri.ca
      • Contact: Tiago Mestre, MSc, MD; Phone Number: 18986 613-798-5555; Email: tmestre@toh.ca
      • Principal Investigator: Tiago Mestre, MSc, MD
    • Toronto, Ontario, Canada, M5T 2S8
      • Recruiting
      • Toronto Western Hospital
      • Contact: Alison Tian; Phone Number: 3415 416-603-5800; Email: Alison.Tian@uhnresearch.ca
      • Contact: Susan Fox, MBChB, MRCP, PhD; Phone Number: 416-699-9837; Email: Sfox@uhnresearch.ca
      • Principal Investigator: Susan Fox, MBChB, MRCP, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• PD as defined by United Kingdom PD Society Brain Bank criteria
• Moderate-to-severe sialorrhea defined by a score in the item 2.2 of the MDS-UPDRS greater than 2

Exclusion Criteria:

1. Other idiopathic parkinsonian syndromes, e.g., Progressive Supranuclear Palsy, Cortico-basal syndrome, or Multiple System Atrophy
2. Secondary parkinsonian syndromes (drug-induced, traumatic, encephalitic or vascular)
3. Change in antiparkinsonian medication one month prior to enrolment
4. Prior use of glycopyrrolate with or without known hypersensitivity will be considered an exclusion criterion, as it increases the risk of unblinding due to prior knowledge of potential side effects or therapeutic benefit
5. Change in the dose one month prior to enrolment of other anticholinergic agents or other drugs potentially affecting saliva production, such as tricyclic antidepressants, MAO-A inhibitors, neuroleptics (including clozapine and quetiapine more frequently used in PD) or hypnotics. These medication will remain in a constant dose throughout the trial;
6. Concomitant use of solid oral dosage forms of potassium chloride;
7. Pregnancy, breastfeeding, and premenopausal females or males not using adequate contraception; medically acceptable birth control methods for this study include: (1) Abstinence (no sexual intercourse); (2) Intrauterine device (IUD); (3) Diaphragm with spermicide; (4) Condom with spermicide; and (5) Oral contraceptives (birth control pills) + condom/diaphragm with spermicide.
8. Moderate-to-severe constipation in spite of optimal treatment (MDS-UPDRS, item 1.11>2);
9. Conditions that preclude anticholinergic therapy, e.g., documented history or symptoms suggestive of inflammatory bowel disease, glaucoma, myasthenia gravis, prostatic hypertrophy or obstructive urinary symptoms;
10. Conditions that can be exacerbated by anticholinergic effects of glycopyrrolate, e.g., documented history or symptoms suggestive of congestive heart failure, coronary heart disease, gastro-esophageal reflux disease or hyperthyroidism;
11. Uncontrolled arterial hypertension (TAS>140 mmHg or TAD>90 mmHg, using an electronic sphygmomanometer and standardized procedure16);
12. Tachyarrhythmia (interval RR <0.6 sec.);
13. TSH<0.4 mIU/L;
14. Liver dysfunction (AST, ALT, ALP >2xUpper Normal Limit);
15. Renal dysfunction (creatinine clearance <50 mL/min), as glycopyrrolate has predominant renal clearance;
16. Inability or unwillingness of subject or legal guardian/representative to give written informed consent;
17. Clinical significant lactose intolerance or known hypersensitivity to any of the study medication excipients
18. Participation in another investigational study at the time of recruitment or during the prior month.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Group; This arm will receive the study drug glycopyrrolate.	Drug: Glycopyrrolate; Drug to reduce drooling in patients with Parkinson's Decease.
Placebo Comparator: Placebo Group; Control arm to receive placebo	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean sialorrhea related-disability at end of treatment (day 90) measured by the patient/caregiver-rated ROMP-saliva.	90 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean score in sialorrhea severity at end of treatment (day 90) measured by the sialorrhea scoring scale	90 days
Proportion of participants with a reduction of severity of sialorrhea in at least one point from baseline to end of treatment (day 90), measured by the MDS-UPDRS, item 2.2.	90 days

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Tiago Mestre, MSc, MD, The Ottawa Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Anticipated): October 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: January 21, 2015
• First Submitted That Met QC Criteria: March 5, 2015
• First Posted (Estimate): March 6, 2015

Study Record Updates

• Last Update Posted (Actual): April 17, 2018
• Last Update Submitted That Met QC Criteria: April 13, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: droooling, sialorrhea, parkinson's disease, parkinsons
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stomatognathic Diseases; Mouth Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Salivary Gland Diseases; Parkinson Disease; Sialorrhea; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Glycopyrrolate
• Other Study ID Numbers: OttawaHRI REB 2015-0043

Plan for Individual participant data (IPD)

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