Domperidone in Secondary Progressive Multiple Sclerosis (SPMS)

NCT02308137 | Completed Phase 2 DMC

• 1 other identifier: Domperidone_MS01
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis, Secondary Progressive

Outcome Measures

Primary Outcomes (1)

• Timed 25-Foot Walk (T25W)

  quantitative ambulation performance test

  up to 12 months

Secondary Outcomes (5)

• 9-Hole Peg Test

  administered at baseline, one month, 6 months, and 12 months

• Symbol Digit Modalities Test

  administered at baseline, one month, 6 months, and 12 months

• Functional Systems and Expanded Disability Status Scale (EDSS)

  administered at baseline, one month, 6 months, and 12 months

• Modified Fatigue Impact Scale (MFIS)

  administered at baseline, one month, 6 months, and 12 months

• Multiple Sclerosis Quality of Life Scale 54 item version

  administered at baseline, one month, 6 months, and 12 months

Study Arms (1)

Domperidone

EXPERIMENTAL

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

Drug: Domperidone

Interventions

Domperidone DRUG

Simon-2-stage design for domperidone futility

Also known as: domperidone maleate

Domperidone

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Calgary: lead
• Alberta Innovates Health Solutions: collaborator

Study Sites (1)

Calgary MS Clinic at Foothills Medical Centre

Calgary, Alberta, T2N 2T9, Canada

Location

Related Publications (11)

• 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.

  PMID: 11006371 BACKGROUND

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

  PMID: 22466660 BACKGROUND

• 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.

  PMID: 2597989 BACKGROUND

• 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.

  PMID: 23007702 BACKGROUND

• 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.

  PMID: 16545751 BACKGROUND

• 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.

  PMID: 16921173 BACKGROUND

• 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.

  PMID: 23026979 BACKGROUND

• 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.

  PMID: 20687779 BACKGROUND

• 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.

  PMID: 22933621 BACKGROUND

• 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.

  PMID: 9307263 BACKGROUND

• 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.

  PMID: 34038379 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Interventions

Domperidone

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Marcus W Koch, MD, PhD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neurologist, Assistant Professor

Study Record Dates

• First Submitted: December 2, 2014
• First Posted: December 4, 2014
• Study Start: February 1, 2015
• Primary Completion: January 3, 2020
• Study Completion: January 3, 2020
• Last Updated: February 24, 2020

Record last verified: 2020-02

Locations

CA (1)