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

Study Overview
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Brief Summary
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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.

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

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

Conditions
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Sialorrhea, Parkinson's Disease

Intervention / Treatment
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* Drug: Glycopyrrolate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: Other idiopathic parkinsonian syndromes, e.g., Progressive Supranuclear Palsy, Cortico-basal syndrome, or Multiple System Atrophy Secondary parkinsonian syndromes (drug-induced, traumatic, encephalitic or vascular) Change in antiparkinsonian medication one month prior to enrolment 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 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; Concomitant use of solid oral dosage forms of potassium chloride; 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. Moderate-to-severe constipation in spite of optimal treatment (MDS-UPDRS, item 1.11>2); 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; 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; Uncontrolled arterial hypertension (TAS>140 mmHg or TAD>90 mmHg, using an electronic sphygmomanometer and standardized procedure16); Tachyarrhythmia (interval RR <0.6 sec.); TSH<0.4 mIU/L; Liver dysfunction (AST, ALT, ALP >2xUpper Normal Limit); Renal dysfunction (creatinine clearance <50 mL/min), as glycopyrrolate has predominant renal clearance; Inability or unwillingness of subject or legal guardian/representative to give written informed consent; Clinical significant lactose intolerance or known hypersensitivity to any of the study medication excipients Participation in another investigational study at the time of recruitment or during the prior month.

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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droooling, sialorrhea, parkinson's disease, parkinsons