- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02308137
Domperidone in Secondary Progressive Multiple Sclerosis (SPMS)
February 20, 2020 updated by: Dr. Marcus Werner Koch, University of Calgary
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)
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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
Study Type
Interventional
Enrollment (Actual)
64
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Alberta
-
Calgary, Alberta, Canada, T2N 2T9
- Calgary MS Clinic at Foothills Medical Centre
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 60 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Domperidone
Treatment: Oral domperidone four times daily Target dose: 40mg per day Duration: 1 year
|
Simon-2-stage design for domperidone futility
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Timed 25-Foot Walk (T25W)
Time Frame: up to 12 months
|
quantitative ambulation performance test
|
up to 12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
9-Hole Peg Test
Time Frame: administered at baseline, one month, 6 months, and 12 months
|
brief, standardized, quantitative test of upper extremity
|
administered at baseline, one month, 6 months, and 12 months
|
Symbol Digit Modalities Test
Time Frame: administered at baseline, one month, 6 months, and 12 months
|
measures cognitive processing speed and working memory
|
administered at baseline, one month, 6 months, and 12 months
|
Functional Systems and Expanded Disability Status Scale (EDSS)
Time Frame: administered at baseline, one month, 6 months, and 12 months
|
EDSS is the standard measure of neurologic impairment that is used to describe disability in MS.
The neurological assessment comprises seven functional systems.
|
administered at baseline, one month, 6 months, and 12 months
|
Modified Fatigue Impact Scale (MFIS)
Time Frame: administered at baseline, one month, 6 months, and 12 months
|
structured, self-report questionnaire with 21 itmes concerning how fatigue impacts patient's life
|
administered at baseline, one month, 6 months, and 12 months
|
Multiple Sclerosis Quality of Life Scale 54 item version
Time Frame: administered at baseline, one month, 6 months, and 12 months
|
54-item multidimensional health-related quality of life measure that combines both generic and MS-specific items
|
administered at baseline, one month, 6 months, and 12 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Marcus W Koch, MD, PhD, University of Calgary
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Rudick R, Antel J, Confavreux C, Cutter G, Ellison G, Fischer J, Lublin F, Miller A, Petkau J, Rao S, Reingold S, Syndulko K, Thompson A, Wallenberg J, Weinshenker B, Willoughby E. Recommendations from the National Multiple Sclerosis Society Clinical Outcomes Assessment Task Force. Ann Neurol. 1997 Sep;42(3):379-82. doi: 10.1002/ana.410420318.
- Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000 Sep 28;343(13):938-52. doi: 10.1056/NEJM200009283431307. No abstract available.
- Lassmann H, van Horssen J, Mahad D. Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol. 2012 Nov 5;8(11):647-56. doi: 10.1038/nrneurol.2012.168. Epub 2012 Sep 25.
- Nylander A, Hafler DA. Multiple sclerosis. J Clin Invest. 2012 Apr;122(4):1180-8. doi: 10.1172/JCI58649. Epub 2012 Apr 2.
- Weinshenker BG, Bass B, Rice GP, Noseworthy J, Carriere W, Baskerville J, Ebers GC. The natural history of multiple sclerosis: a geographically based study. 2. Predictive value of the early clinical course. Brain. 1989 Dec;112 ( Pt 6):1419-28. doi: 10.1093/brain/112.6.1419.
- Rovaris M, Confavreux C, Furlan R, Kappos L, Comi G, Filippi M. Secondary progressive multiple sclerosis: current knowledge and future challenges. Lancet Neurol. 2006 Apr;5(4):343-54. doi: 10.1016/S1474-4422(06)70410-0.
- Patrikios P, Stadelmann C, Kutzelnigg A, Rauschka H, Schmidbauer M, Laursen H, Sorensen PS, Bruck W, Lucchinetti C, Lassmann H. Remyelination is extensive in a subset of multiple sclerosis patients. Brain. 2006 Dec;129(Pt 12):3165-72. doi: 10.1093/brain/awl217. Epub 2006 Aug 18. Erratum In: Brain. 2007 Mar;130(Pt 3):879.
- Franklin RJ, ffrench-Constant C, Edgar JM, Smith KJ. Neuroprotection and repair in multiple sclerosis. Nat Rev Neurol. 2012 Nov 5;8(11):624-34. doi: 10.1038/nrneurol.2012.200. Epub 2012 Oct 2.
- Tselis A, Khan OA, Lisak RP. Approaches to neuroprotective strategies in multiple sclerosis. Expert Opin Pharmacother. 2010 Dec;11(17):2869-78. doi: 10.1517/14656566.2010.508070. Epub 2010 Aug 5.
- Zhornitsky S, Yong VW, Weiss S, Metz LM. Prolactin in multiple sclerosis. Mult Scler. 2013 Jan;19(1):15-23. doi: 10.1177/1352458512458555. Epub 2012 Aug 29.
- Koch MW, Sage K, Kaur S, Kim J, Cerchiaro G, Yong VW, Cutter GR, Metz LM. Repurposing Domperidone in Secondary Progressive Multiple Sclerosis: A Simon 2-Stage Phase 2 Futility Trial. Neurology. 2021 May 4;96(18):e2313-e2322. doi: 10.1212/WNL.0000000000011863. Epub 2021 Mar 23.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 1, 2015
Primary Completion (Actual)
January 3, 2020
Study Completion (Actual)
January 3, 2020
Study Registration Dates
First Submitted
December 2, 2014
First Submitted That Met QC Criteria
December 3, 2014
First Posted (Estimate)
December 4, 2014
Study Record Updates
Last Update Posted (Actual)
February 24, 2020
Last Update Submitted That Met QC Criteria
February 20, 2020
Last Verified
February 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Immune System Diseases
- Neoplasms
- Demyelinating Autoimmune Diseases, CNS
- Autoimmune Diseases of the Nervous System
- Demyelinating Diseases
- Autoimmune Diseases
- Neoplastic Processes
- Multiple Sclerosis
- Multiple Sclerosis, Chronic Progressive
- Sclerosis
- Neoplasm Metastasis
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiemetics
- Gastrointestinal Agents
- Dopamine Agents
- Dopamine Antagonists
- Domperidone
Other Study ID Numbers
- Domperidone_MS01
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Sclerosis, Secondary Progressive
-
Casa Sollievo della Sofferenza IRCCSNeurocenter of Southern Switzerland; Associazione Revert ONLUS; Fondazione Cellule...CompletedSecondary-progressive Multiple SclerosisItaly, Switzerland
-
BioMS Technology Corp.TerminatedMultiple Sclerosis, Secondary Progressive
-
Tiziana Life Sciences LTDWithdrawnMultiple Sclerosis | Primary Progressive Multiple Sclerosis | Secondary Progressive Multiple Sclerosis
-
University College, LondonLondon School of Hygiene and Tropical Medicine; The Leeds Teaching Hospitals... and other collaboratorsActive, not recruitingSecondary Progressive Multiple Sclerosis (SPMS)United Kingdom
-
Stem Cell Medicine Ltd.Not yet recruitingSecondary Progressive Multiple Sclerosis (SPMS)Israel
-
University of MinnesotaMallinckrodtTerminatedPrimary Progressive Multiple Sclerosis | Secondary Progressive Multiple Sclerosis | Progressive Relapsing Multiple SclerosisUnited States
-
State University of New York at BuffaloCompletedSecondary-progressive Multiple SclerosisUnited States
-
Novartis PharmaceuticalsActive, not recruitingRelapsing-remitting Multiple Sclerosis | Active Secondary Progressive Multiple SclerosisJapan
-
University of UtahCompletedMultiple Sclerosis | Multiple Sclerosis, Secondary Progressive | Secondary Progressive Multiple SclerosisUnited States
-
Novartis PharmaceuticalsActive, not recruitingActive Secondary Progressive Multiple SclerosisItaly
Clinical Trials on Domperidone
-
Hamilton Health Sciences CorporationThe Physicians' Services Incorporated FoundationTerminatedInsufficient Breastmilk ProductionCanada
-
Arnold, George, M.D.Unknown
-
David J. Lederer, M.D.TerminatedGastroesophageal Reflux | GastroparesisUnited States
-
Eastern Regional Medical CenterAvailableOncology Patients With GastroparesisUnited States
-
University of CalgaryAlberta Innovates Health SolutionsCompletedMultiple Sclerosis, Relapsing-RemittingCanada
-
Nantes University HospitalCompletedPrematurity and Feeding IntoleranceFrance
-
Aurora Health CareAvailable
-
University Health Network, TorontoTerminatedParkinson's Disease | Peripheral EdemaCanada
-
Sunnybrook Health Sciences CentreCompletedLow Milk SupplyCanada