Domperidone in Secondary Progressive Multiple Sclerosis (SPMS)

Study Overview
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Brief Summary
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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
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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

Official Title
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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)

Conditions
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Multiple Sclerosis, Secondary Progressive

Intervention / Treatment
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* Drug: Domperidone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Domperidone<br>Treatment: Oral domperidone four times daily Target dose: 40mg per day Duration: 1 year | Drug: Domperidone<br>* Simon-2-stage design for domperidone futility<br>* Other names: domperidone maleate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Timed 25-Foot Walk (T25W) | quantitative ambulation performance test | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 9-Hole Peg Test | brief, standardized, quantitative test of upper extremity | administered at baseline, one month, 6 months, and 12 months | 
| Symbol Digit Modalities Test | 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) | 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) | 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 | 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 |