Domperidone in Secondary Progressive Multiple Sclerosis (SPMS)

Sponsor

University of Calgary (Other)

Overall Status

Completed

CT.gov ID

NCT02308137

Collaborator

Alberta Innovates Health Solutions (Other)

Enrollment

Location

Arm

Actual Duration (Months)

1.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis, Secondary Progressive	Drug: Domperidone	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

64 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Feb 1, 2015

Actual Primary Completion Date :

Jan 3, 2020

Actual Study Completion Date :

Jan 3, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Domperidone Treatment: Oral domperidone four times daily Target dose: 40mg per day Duration: 1 year	Drug: Domperidone Simon-2-stage design for domperidone futility Other Names: domperidone maleate

Arm

Intervention/Treatment

Experimental: Domperidone

Treatment: Oral domperidone four times daily Target dose: 40mg per day Duration: 1 year

Drug: Domperidone

Simon-2-stage design for domperidone futility

Other Names:

domperidone maleate

Outcome Measures

Primary Outcome Measures

Timed 25-Foot Walk (T25W) [up to 12 months]
quantitative ambulation performance test

Secondary Outcome Measures

9-Hole Peg Test [administered at baseline, one month, 6 months, and 12 months]
brief, standardized, quantitative test of upper extremity
Symbol Digit Modalities Test [administered at baseline, one month, 6 months, and 12 months]
measures cognitive processing speed and working memory
Functional Systems and Expanded Disability Status Scale (EDSS) [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.
Modified Fatigue Impact Scale (MFIS) [administered at baseline, one month, 6 months, and 12 months]
structured, self-report questionnaire with 21 itmes concerning how fatigue impacts patient's life
Multiple Sclerosis Quality of Life Scale 54 item version [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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