Effect of Short-term Motilitone Therapy on Health-related Quality of Life in PD Patients With Gastrointestinal Symptoms (PASS-GI)

Effect of Short-term Motilitone Therapy on Health-related Quality of Life in Parkinson's Disease Patients With Gastrointestinal Symptoms: a Multicenter, Double-blind Randomized, Placebo-controlled Trial

The purpose of this study is to determine whether DA-9701(Motilitone) is effective and safe for the treatment on health-related quality of life in Parkinson's disease (PD) patients with gastrointestinal symptoms.

Study Overview

• Status: Completed
• Conditions: Dyspepsia; Parkinson Disease
• Intervention / Treatment: Drug: DA-9701; Drug: DA-9701 placebo

Detailed Description

Gastrointestinal (GI) symptoms are frequently complained by PD patients. To improve their symptoms, prokinetics are often used in clinics. However, some prokinetics are dopamine receptor antagonist which can aggravate motor symptoms of PD patients or develop tardive dyskinesia when it affects dopamine receptors of the brain.

DA-9701 (Motilitone) is recently developed herbal medication which has both 5-HT4 agonism and D2 antagonism. Furthermore, it does not cross the blood brain barrier that can be safely used in PD patients. Hypothetically it has a potential to be a good choice for the treatment of GI symptoms of PD patients. However, there has been no study that evaluates its efficacy and safety by randomized clinical trials in PD patients.

This study will evaluate the efficacy and safety of DA-9701 in the double-blind placebo-controlled phase 1 (4 weeks), and the long-term safety of DA-9701 in the open-label phase 2 (8 weeks after phase 1).

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Boramae Hospital
  • Seoul, Korea, Republic of
    • Hanyang University Medical Center
  • Seoul, Korea, Republic of
    • Veterans Healthcare Service Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects were enrolled voluntarily and understood the contents of this clinical trial.
• Male or female Parkinson disease (PD) patients between 50 and 80 years
• Subjects who had not received prokinetics (itopride, mosapride, Corydalis tuber, levosulpiride, domperidone, etc.) at least 2 months prior to baseline visit
• Subjects complained at least one symptom of the following that suggests abnormal bowel functions: anorexia, nausea, abdominal distension, dyspepsia, early satiety, dysphagia, foreign body sensation associated with a meal, symptoms of gastroesophageal reflux, constipation, and defecation problem.

Exclusion Criteria:

• History of a gastrointestinal operation
• Subjects with active gastrointestinal diseases under treatment of gastroenterology within 1 month
• Existence of clinically significant cognitive decline or K-Minimental Status Exam score 20 or less
• Subjects had depression or other psychiatric disorders treated with medications such as antidepressants or antipsychotics; mood tranquilizers, benzodiazepines, and sleep pills were permitted with fixed dose during a period of the clinical trial
• Subjects with severe active comorbidities which could interfere the quality of life of the patient
• Subjects with medical conditions which make difficult to be enrolled to the trial judged by clinicians
• Subjects with hypersensitivity or adverse event related to DA-9701 (Motilitone)
• Prior participation to other clinical trials within 3 months

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
Experimental: Motilitone arm; DA-9701 (Motilitone) 30mg 1T three times per day for 4+8 weeks	Drug: DA-9701; DA-9701 30mg Tablet; Other Names: Motilitone
Placebo Comparator: Placebo arm; DA-9701 placebo 30mg 1T three times per day for 4 weeks, DA-9701 (Motilitone) 30mg 1T three times per day for 8 weeks	Drug: DA-9701; DA-9701 30mg Tablet; Other Names: Motilitone; Drug: DA-9701 placebo; Placebo pill manufactured to mask DA-9701 30mg Tablet; Other Names: Motilitone placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Nepean dyspepsia index-Korean version scores	The Nepean dyspepsia index is a tool to measure gastrointestinal symptoms	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in bowel movements per day assessed by a bowel habit questionnaire.	Mean bowel movements per day of recent 1 week will be asked using the bowel habit questionnaire.	4 weeks, 12 weeks
Change in frequency of early satiety per day assessed by a bowel habit questionnaire.	Mean frequency of early satiety per day of recent 1 week will be asked using the bowel habit questionnaire. The frequency will be categorized as following: 0, no event; 1, once a day; 2, twice a day; 3, every meal.	4 weeks, 12 weeks
Change in frequency of gastric fullness after a meal per day assessed by a bowel habit questionnaire.	Mean frequency of gastric fullness after a meal per day of recent 1 week will be asked using the bowel habit questionnaire. The frequency will be categorized as following: 0, no event; 1, once a day; 2, twice a day; 3, every meal.	4 weeks, 12 weeks
Change in severity of epigastric pain assessed by a bowel habit questionnaire.	Existence and severity of epigastric pain of recent 1 week will be asked using the bowel habit questionnaire. The severity will be categorized as following: 0, no event; 1, mild; 2, moderate; 3, severe; 4, very severe.	4 weeks, 12 weeks
Change in the Bristol stool scale score	This is a descriptive picture plate which patients can choose the type of their stool	4 weeks, 12 weeks
Change in the Unified Parkinson's disease rating scale (UPDRS) scores	This is a measure of the severity of Parkinson's disease	4 weeks, 12 weeks
Change in the Parkinson's disease quality of life scale (PDQ-39) scores	This is a measure of everyday quality of life affected by Parkinson's disease	4 weeks, 12 weeks
Change in the Patient global improvement (PGI) scores	This is a measure of patients perception of change in their gastrointestinal symptoms	4 weeks, 12 weeks
Change in the Clinician global improvement (CGI) scores	This is a measure of clinican's assessment of global clinical status of the patient	4 weeks, 12 weeks
Change in the Nepean dyspepsia index-Korean version scores	This is a measure of changes in gastrointestinal symptoms at the end of this trial	12 weeks

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Samsung Medical Center; Korea University Guro Hospital; Hanyang University; SMG-SNU Boramae Medical Center; Seoul Veterans Hospital
• Investigators: Principal Investigator: Jee-Young Lee, MD, PhD, SMG-SNU Boramae Medical Center

Publications and helpful links

General Publications

• Choi JH, Lee JY, Cho JW, Koh SB, Yang YS, Yoo D, Shin CM, Kim HT. Double-Blind, Randomized, Placebo-Controlled Trial of DA-9701 in Parkinson's Disease: PASS-GI Study. Mov Disord. 2020 Nov;35(11):1966-1976. doi: 10.1002/mds.28219. Epub 2020 Aug 6.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: May 9, 2016
• First Submitted That Met QC Criteria: May 14, 2016
• First Posted (Estimate): May 17, 2016

Study Record Updates

• Last Update Posted (Actual): March 28, 2019
• Last Update Submitted That Met QC Criteria: March 26, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Digestive; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyspepsia; Parkinson Disease
• Other Study ID Numbers: 26-2016-11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: DATA including IPD can be shared individually upon request by qualified investigators excluding patients' personal information
• IPD Sharing Time Frame: The information will be judged by the principal investigator upon individual request.
• IPD Sharing Access Criteria: The information will be judged by the principal investigator upon individual request.