Domperidone in Secondary Progressive Multiple Sclerosis (SPMS)

Multiple Sclerosis, Secondary Progressive Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02308137
• Other study ID #: Domperidone_MS01
• Status: Completed
• Phase: Phase 2
• Start date: February 2015
• Est. completion date: January 3, 2020

Study information

• Verified date: February 2020
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: January 3, 2020
• Est. primary completion date: January 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Multiple Sclerosis, Secondary Progressive
• Neoplasm Metastasis
• Sclerosis

Intervention

Drug:
• Domperidone
Simon-2-stage design for domperidone futility

Locations

Country	Name	City	State
Canada	Calgary MS Clinic at Foothills Medical Centre	Calgary	Alberta

Sponsors (2)

Lead Sponsor	Collaborator
University of Calgary	Alberta Innovates Health Solutions

Country where clinical trial is conducted

Canada, 

References & Publications (10)

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. Review. — View Citation

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. Review. — View Citation

Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000 Sep 28;343(13):938-52. Review. — View Citation

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

Patrikios P, Stadelmann C, Kutzelnigg A, Rauschka H, Schmidbauer M, Laursen H, Sorensen PS, Brück W, Lucchinetti C, Lassmann H. Remyelination is extensive in a subset of multiple sclerosis patients. Brain. 2006 Dec;129(Pt 12):3165-72. Epub 2006 Aug 18. Erratum in: Brain. 2007 Mar;130(Pt 3):879. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Timed 25-Foot Walk (T25W)	quantitative ambulation performance test	up to 12 months
Secondary	9-Hole Peg Test	brief, standardized, quantitative test of upper extremity	administered at baseline, one month, 6 months, and 12 months
Secondary	Symbol Digit Modalities Test	measures cognitive processing speed and working memory	administered at baseline, one month, 6 months, and 12 months
Secondary	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
Secondary	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
Secondary	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