Multiple Sclerosis, Secondary ProgressivePhase 2NCT02308137
Domperidone in Secondary Progressive Multiple Sclerosis (SPMS)
A Phase 2 study testing Domperidone in people with Multiple Sclerosis, Secondary Progressive, run by University of Calgary at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis, Secondary Progressive
- What is being tested?
- Domperidone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteCanada
- Study dates
- Feb 2015to 3 Jan 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
Calgary MS Clinic at Foothills Medical Centre
Calgary, Alberta, T2N 2T9
About this study
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)
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.
Read the 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
- Being tested
- Domperidone
- Medical subject headings
- Multiple Sclerosis, Chronic Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DomperidoneDrug
Also called domperidone maleate
Simon-2-stage design for domperidone futility
| Study group | Role | What they receive |
|---|---|---|
| Domperidone | Experimental | Treatment: Oral domperidone four times daily Target dose: 40mg per day Duration: 1 year Receives: Drug: Domperidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Timed 25-Foot Walk (T25W)
quantitative ambulation performance test
Measured: up to 12 months
Secondary outcomes (5)
9-Hole Peg Test
brief, standardized, quantitative test of upper extremity
Measured: administered at baseline, one month, 6 months, and 12 months
Symbol Digit Modalities Test
measures cognitive processing speed and working memory
Measured: administered at baseline, one month, 6 months, and 12 months
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.
Measured: administered at baseline, one month, 6 months, and 12 months
Modified Fatigue Impact Scale (MFIS)
structured, self-report questionnaire with 21 itmes concerning how fatigue impacts patient's life
Measured: administered at baseline, one month, 6 months, and 12 months
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
Measured: administered at baseline, one month, 6 months, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2014 (estimated)
- Study startFeb 2015
- Primary completion3 Jan 2020
- Study completion3 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Secondary ProgressiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- Alberta Innovates Health Solutions
- Responsible party
- Principal investigator, Dr. Marcus Werner Koch, University of Calgary
- Investigators
- Marcus W Koch, MD, PhD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02308137
- Sponsor's protocol ID
- Domperidone_MS01
- Status last verified
- Feb 2020
- First submitted
- 2 Dec 2014
- Last updated
- 24 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 11006371Nylander A, Hafler DA. Multiple sclerosis. J Clin Invest. 2012 Apr;122(4):1180-8. doi: 10.1172/JCI58649. Epub 2012 Apr 2.
PubMed 22466660Weinshenker 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.
PubMed 2597989Lassmann 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.
PubMed 23007702Rovaris 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.
PubMed 16545751Patrikios 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.
PubMed 16921173Franklin 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.
PubMed 23026979Tselis 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.
PubMed 20687779Zhornitsky 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.
PubMed 22933621Rudick 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.
PubMed 9307263Koch 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.
PubMed 34038379
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02308137
- Acronym / sponsor ID
- Domperidone_MS01
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- Alberta Innovates Health Solutions
- Study start
- Feb 2015 (actual)
- Primary completion
- 3 Jan 2020 (actual)
- Study completion
- 3 Jan 2020 (actual)
- First posted
- 4 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Domperidone | Experimental | Drug: DomperidoneTreatment: Oral domperidone four times daily Target dose: 40mg per day Duration: 1 year |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DomperidoneAlso: domperidone maleateSimon-2-stage design for domperidone futility | Drug | Domperidone |
Primary outcome
Timed 25-Foot Walk (T25W)
Time frame: up to 12 months
quantitative ambulation performance test
5 secondary outcomes
9-Hole Peg Test
Time frame: administered at baseline, one month, 6 months, and 12 months
Symbol Digit Modalities Test
Time frame: administered at baseline, one month, 6 months, and 12 months
Functional Systems and Expanded Disability Status Scale (EDSS)
Time frame: administered at baseline, one month, 6 months, and 12 months
Modified Fatigue Impact Scale (MFIS)
Time frame: administered at baseline, one month, 6 months, and 12 months
Multiple Sclerosis Quality of Life Scale 54 item version
Time frame: administered at baseline, one month, 6 months, and 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2020.
- Background: PubMed 11006371Noseworthy 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: PubMed 22466660Nylander A, Hafler DA. Multiple sclerosis. J Clin Invest. 2012 Apr;122(4):1180-8. doi: 10.1172/JCI58649. Epub 2012 Apr 2.
- Background: PubMed 2597989Weinshenker 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: PubMed 23007702Lassmann 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: PubMed 16545751Rovaris 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: PubMed 16921173Patrikios 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: PubMed 23026979Franklin 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: PubMed 20687779Tselis 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: PubMed 22933621Zhornitsky 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.
- Background: PubMed 9307263Rudick 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.
- Derived from this study: PubMed 34038379Koch 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marcus W Koch, MD, PhD principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Domperidone in people with Multiple Sclerosis, Secondary Progressive, run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Timed 25-Foot Walk (T25W) (time frame: up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02308137, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2020.