Domperidone in Secondary Progressive Multiple Sclerosis (SPMS)
Primary Purpose
Multiple Sclerosis, Secondary Progressive
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Domperidone
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis, Secondary Progressive
Eligibility Criteria
Inclusion Criteria:
- written informed consent obtained
- with Multiple Sclerosis, and with secondary progressive disease course
- screening Expanded Disability Status Scale (EDSS) score between 4.0 and 6.5 inclusive
- screening timed 25 foot walk (average of two trials) lof 9 seconds or more
Exclusion Criteria:
- Long QT interval, defined as corrected QT interval of more than 470 msec in men and more than 450 msec in women on baseline ECG
- Patients with known long-QT syndrome
- Patients with known ventricular arrhythmia
- Patients with a known electrolyte disturbance
- Patients undergoing treatment with drugs that increase the QTc interval
- Patients undergoing treatment with drugs that inhibit CYP3A4, in particular: Ketoconazole, Fluconazole, Erythromycin, Clarithromycin, Ritonavir
- Patients with a history of breast cancer or carcinoma in situ
- Patients with known renal insufficiency
- Patients with known allergy or other intolerability to domperidone
- Patients currently using Fampridine or 4-aminopyridine
- Patients planning to start Fampridine or 4-aminopyridine during the study period
- Patients planning to start Baclofen or Tizanidine during the duration of the study
- Patients planning to increase or decrease their dose of Baclofen or Tizanidine during the study period
- Patients planning to receive treatment with Botulinum toxin in the leg muscles during the duration of the study
- Patients with a significiant hepatic impairment
- Patients with a prolactinoma
- Patients in whom gastrointestinal stimulation could be dangerous
- Patients using MAO inhibitors
- Patients with a history of breast cancer
- Pregnant or breast-feeding women
Sites / Locations
- Calgary MS Clinic at Foothills Medical Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Domperidone
Arm Description
Treatment: Oral domperidone four times daily Target dose: 40mg per day Duration: 1 year
Outcomes
Primary Outcome Measures
Timed 25-Foot Walk (T25W)
quantitative ambulation performance test
Secondary Outcome Measures
9-Hole Peg Test
brief, standardized, quantitative test of upper extremity
Symbol Digit Modalities Test
measures cognitive processing speed and working memory
Functional Systems and Expanded Disability Status Scale (EDSS)
EDSS is the standard measure of neurologic impairment that is used to describe disability in MS. The neurological assessment comprises seven functional systems.
Modified Fatigue Impact Scale (MFIS)
structured, self-report questionnaire with 21 itmes concerning how fatigue impacts patient's life
Multiple Sclerosis Quality of Life Scale 54 item version
54-item multidimensional health-related quality of life measure that combines both generic and MS-specific items
Full Information
NCT ID
NCT02308137
First Posted
December 2, 2014
Last Updated
February 20, 2020
Sponsor
University of Calgary
Collaborators
Alberta Innovates Health Solutions
1. Study Identification
Unique Protocol Identification Number
NCT02308137
Brief Title
Domperidone in Secondary Progressive Multiple Sclerosis (SPMS)
Official Title
Open-label, Single-center, Single-arm Futility Trial Evaluating Oral Domperidone 10mg QID for Reducing Progression of Disability in Patients With Secondary Progressive Multiple Sclerosis (SPMS)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
February 2015 (Actual)
Primary Completion Date
January 3, 2020 (Actual)
Study Completion Date
January 3, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Calgary
Collaborators
Alberta Innovates Health Solutions
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this clinical trial is to determine if Domperidone in a dose of 40 mg daily can prevent worsening of walking ability in people secondary progressive MS. The number of participants in this study will be 62. A maximum of 75 people with secondary progressive MS will be included. Each patient will be followed for 12 months from inclusion. Domperidone is a medication which has been shown to increase levels of the hormone prolactin. The best understood function of prolactin is the stimulation of milk production in women after delivery. However, the increase in prolactin levels seen in patients treated with standard doses of Domperidone (in doses of up to 80mg per day) usually does not lead to clinical symptoms. Prolactin has been shown to improve myelin repair in mice. Domperidone therefore may also improve myelin repair in people with MS. Domperidone is currently approved in Canada to treat slow moving bowels and nausea, for instance in patients with Parkinson's Disease or Diabetes Mellitus, where too slowly moving bowels can cause constipation. Domperidone is available as a tablet that is usually taken four times per day. Doses up to 80mg per day may be used but we estimate that a dose of only 40mg daily will be needed to stimulate myelin repair. Domperidone is usually well tolerated.
Detailed Description
Primary objective
To demonstrate non-futility of domperidone for reducing progression of disability, as measured with the timed 25 foot walk (T25FW), in secondary progressive Multiple Sclerosis (SPMS).
Secondary objectives
To assess the safety of domperidone in the study population for the duration of the study.
To assess the effect of domperidone on hand dexterity as measured with the 9HPT
To assess the effect of domperidone on cognition, as measured with the SDMT
To assess the effect of domperidone on health related quality of life, as measured with the MSQOL-54
To assess the effect of domperidone on fatigue, as measured with the MFIS
To establish the Simon-2-stage model as a study model in MS research. The application of this methodology to studies in progressive MS will have important consequences for the design and conduct of clinical and translational research in progressive MS, in particular for phase II trials in progressive MS
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Secondary Progressive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Domperidone
Arm Type
Experimental
Arm Description
Treatment: Oral domperidone four times daily Target dose: 40mg per day Duration: 1 year
Intervention Type
Drug
Intervention Name(s)
Domperidone
Other Intervention Name(s)
domperidone maleate
Intervention Description
Simon-2-stage design for domperidone futility
Primary Outcome Measure Information:
Title
Timed 25-Foot Walk (T25W)
Description
quantitative ambulation performance test
Time Frame
up to 12 months
Secondary Outcome Measure Information:
Title
9-Hole Peg Test
Description
brief, standardized, quantitative test of upper extremity
Time Frame
administered at baseline, one month, 6 months, and 12 months
Title
Symbol Digit Modalities Test
Description
measures cognitive processing speed and working memory
Time Frame
administered at baseline, one month, 6 months, and 12 months
Title
Functional Systems and Expanded Disability Status Scale (EDSS)
Description
EDSS is the standard measure of neurologic impairment that is used to describe disability in MS. The neurological assessment comprises seven functional systems.
Time Frame
administered at baseline, one month, 6 months, and 12 months
Title
Modified Fatigue Impact Scale (MFIS)
Description
structured, self-report questionnaire with 21 itmes concerning how fatigue impacts patient's life
Time Frame
administered at baseline, one month, 6 months, and 12 months
Title
Multiple Sclerosis Quality of Life Scale 54 item version
Description
54-item multidimensional health-related quality of life measure that combines both generic and MS-specific items
Time Frame
administered at baseline, one month, 6 months, and 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
written informed consent obtained
with Multiple Sclerosis, and with secondary progressive disease course
screening Expanded Disability Status Scale (EDSS) score between 4.0 and 6.5 inclusive
screening timed 25 foot walk (average of two trials) lof 9 seconds or more
Exclusion Criteria:
Long QT interval, defined as corrected QT interval of more than 470 msec in men and more than 450 msec in women on baseline ECG
Patients with known long-QT syndrome
Patients with known ventricular arrhythmia
Patients with a known electrolyte disturbance
Patients undergoing treatment with drugs that increase the QTc interval
Patients undergoing treatment with drugs that inhibit CYP3A4, in particular: Ketoconazole, Fluconazole, Erythromycin, Clarithromycin, Ritonavir
Patients with a history of breast cancer or carcinoma in situ
Patients with known renal insufficiency
Patients with known allergy or other intolerability to domperidone
Patients currently using Fampridine or 4-aminopyridine
Patients planning to start Fampridine or 4-aminopyridine during the study period
Patients planning to start Baclofen or Tizanidine during the duration of the study
Patients planning to increase or decrease their dose of Baclofen or Tizanidine during the study period
Patients planning to receive treatment with Botulinum toxin in the leg muscles during the duration of the study
Patients with a significiant hepatic impairment
Patients with a prolactinoma
Patients in whom gastrointestinal stimulation could be dangerous
Patients using MAO inhibitors
Patients with a history of breast cancer
Pregnant or breast-feeding women
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marcus W Koch, MD, PhD
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
Facility Information:
Facility Name
Calgary MS Clinic at Foothills Medical Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 2T9
Country
Canada
12. IPD Sharing Statement
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Domperidone in Secondary Progressive Multiple Sclerosis (SPMS)
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