Domperidone in Secondary Progressive Multiple Sclerosis (SPMS)
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)
What it found
A paper reports the results; we have not read it yet. See Papers below.
What was tested
Treatment tested
- Domperidone
Dopamine D2 receptor antagonist
What it measured
Main measures
Timed 25-Foot Walk (T25W)
up to 12 months
Disability progressionWalking and mobility
Other measures (5)
9-Hole Peg Test
administered at baseline, one month, 6 months, and 12 months
Disability progressionArm and hand functionSymbol Digit Modalities Test
administered at baseline, one month, 6 months, and 12 months
Thinking and memoryFunctional Systems and Expanded Disability Status Scale (EDSS)
administered at baseline, one month, 6 months, and 12 months
Disability progressionModified Fatigue Impact Scale (MFIS)
administered at baseline, one month, 6 months, and 12 months
FatigueMultiple Sclerosis Quality of Life Scale 54 item version
administered at baseline, one month, 6 months, and 12 months
Quality of life (reported by participants)
Who could take part
Progressive MS · 18 to 60 · EDSS 4.0 to 6.5
Show the full criteria
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
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
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.
Papers
Results
Repurposing Domperidone in Secondary Progressive Multiple Sclerosis: A Simon 2-Stage Phase 2 Futility Trial.Neurology · 2021
Background
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.Background
Nylander A, Hafler DA. Multiple sclerosis. J Clin Invest. 2012 Apr;122(4):1180-8. doi: 10.1172/JCI58649. Epub 2012 Apr 2.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.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.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.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.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.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.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.
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History
Started
Feb 2015
Main results due
Jan 2020
Finished
Jan 2020