Domperidone in Secondary Progressive Multiple Sclerosis (SPMS)

NCT ID: NCT02308137

Last Updated: 2020-02-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

64 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-02-28

Study Completion Date

2020-01-03

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

Conditions

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Multiple Sclerosis, Secondary Progressive

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Domperidone

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

Group Type EXPERIMENTAL

Domperidone

Intervention Type DRUG

Simon-2-stage design for domperidone futility

Interventions

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Domperidone

Simon-2-stage design for domperidone futility

Intervention Type DRUG

Other Intervention Names

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domperidone maleate

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alberta Innovates Health Solutions

OTHER

Sponsor Role collaborator

University of Calgary

OTHER

Sponsor Role lead

Responsible Party

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Dr. Marcus Werner Koch

Neurologist, Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Marcus W Koch, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

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Calgary MS Clinic at Foothills Medical Centre

Calgary, Alberta, Canada

Site Status

Countries

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Canada

References

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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.

Reference Type BACKGROUND
PMID: 11006371 (View on PubMed)

Nylander A, Hafler DA. Multiple sclerosis. J Clin Invest. 2012 Apr;122(4):1180-8. doi: 10.1172/JCI58649. Epub 2012 Apr 2.

Reference Type BACKGROUND
PMID: 22466660 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 2597989 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23007702 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16545751 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16921173 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23026979 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20687779 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22933621 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9307263 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34038379 (View on PubMed)

Other Identifiers

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Domperidone_MS01

Identifier Type: -

Identifier Source: org_study_id

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