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Domperidone in Secondary Progressive Multiple Sclerosis (SPMS)

Phase 2
Completed
Conditions
Multiple Sclerosis, Secondary Progressive
Interventions
Registration Number
NCT02308137
Lead Sponsor
University of Calgary
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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
64
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
DomperidoneDomperidoneTreatment: Oral domperidone four times daily Target dose: 40mg per day Duration: 1 year
Primary Outcome Measures
NameTimeMethod
Timed 25-Foot Walk (T25W)up to 12 months

quantitative ambulation performance test

Secondary Outcome Measures
NameTimeMethod
9-Hole Peg Testadministered at baseline, one month, 6 months, and 12 months

brief, standardized, quantitative test of upper extremity

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

Symbol Digit Modalities Testadministered at baseline, one month, 6 months, and 12 months

measures cognitive processing speed and working memory

Multiple Sclerosis Quality of Life Scale 54 item versionadministered 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

Trial Locations

Locations (1)

Calgary MS Clinic at Foothills Medical Centre

🇨🇦

Calgary, Alberta, Canada

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