Multiple Sclerosis, Relapsing-Remitting Clinical Trial
Official title:
Randomized, Controlled Pilot Trial of Domperidone in Relapsing-Remitting Multiple Sclerosis
Verified date | October 2019 |
Source | University of Calgary |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The first major objective of this pilot trial is to demonstrate that it is possible to study
myelin repair in relapsing-remitting multiple sclerosis (RRMS) patients with enhancing
lesions on MRI by using advanced imaging techniques. To demonstrate that this is possible the
investigators will recruit 24 RRMS patients who are being treated with standard disease
modifying therapy (DMT) and have new lesions identified on clinically indicated brain MRI
scans and measure myelin repair at 16 and 32 weeks using MRI measures of myelin repair. The
second major objective is to determine how much repair occurs in participants treated with
domperidone compared with those who are not treated. This will allow us to design larger
trials to confirm that domperidone improves repair. The study will also confirm the safety
and tolerability of domperidone in RRMS, determine circulating prolactin levels during dosing
with domperidone 10mg three times daily in people with RRMS, and explore the impact of other
clinical factors (such as age) on lesion repair.
In addition, blood will be collected to test for metabolomics and the investigators will bank
blood for future study of biomarkers that can help the investigators better understand MS.
Metabolomics is an experimental test where changes in the pattern of the chemicals in blood
cells are compared at different time points (during and after inflammation). There will be
random changes but changes that are common in most study participants may help identify
chemicals that signal stages in injury or repair. The investigators will also compare the
pattern of change in those with the best repair to those with the worst repair. This may help
identify a chemical that is associated with better or worse repair and help develop new
treatment strategies. There are currently no blood tests that help in the diagnosis of MS,
help determine which drug a person will respond to, or help determine a person's expected MS
outcome. Any such tests would be considered biomarkers.
Status | Completed |
Enrollment | 17 |
Est. completion date | February 2019 |
Est. primary completion date | February 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 60 Years |
Eligibility |
Inclusion Criteria: - Participants must be between age 18 and 60 years. - Sexually active men and women of child-bearing potential, defined as those who are not postmenopausal (24 consecutive months) or permanently sterilised, must agree to use adequate contraception. Adequate contraception is defined as methods of birth control which result in a low failure rate [i.e. less than 1% per year] when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), barrier contraceptives, sexual abstinence or vasectomised partner. Adequate contraception is required during domperidone treatment and for one month after stopping treatment. - Participants must have MS defined according to the McDonald criteria (Polman et al. 2011). - Participants must have RRMS according to Lublin et al. (2014). - Participants must have been treated with a stable approved dose of glatiramer acetate, interferon-beta, fingolimod, dimethyl fumarate, or teriflunomide for at least 6 months. - Participants must be scheduled to have a clinically indicated brain MRI to monitor DMT effectiveness. - Participants must have at least one gadolinium enhancing lesion on their DMT monitoring MRI (screening MRI). - Participants must report at least 80% adherence to their current DMT and have had no treatment discontinuation for one week or longer within the prior 6 months. - Participants must be patients of the Calgary MS Clinic. - Participants must provide written informed consent Exclusion Criteria: - Participants who are pregnant or breastfeeding - Participants in whom it is expected that their current DMT will be discontinued within 16 weeks. Indicators of likely discontinuation will include poor DMT tolerance, a wish by the participant to discontinue the DMT, or a history of poor clinical response to the current DMT (such as a relapse within the previous year while on the current DMT) - Participants who have a long QT interval, defined as corrected QT interval of more than 470 msec in men and more than 450 msec in women, on screening ECG. - Participants with known long-QT syndrome or known cardiac arrhythmia. - Participants who currently or previously have been treated with natalizumab. - Participants who are currently treated with domperidone or have taken it within the previous 3 months. - Participants who are taking drugs which prolong QT intervals or who are treated with drugs that inhibit cytochrome P450 3A4. - Participants who are concurrently treated with drugs that may increase serum prolactin levels. - Participants who have a prolactinoma - Participants who use systemic corticosteroids within the 8 weeks prior to the screening MRI or who use concurrent immunosuppressive medications including systemic corticosteroids. - Participants who have a history of breast cancer or breast carcinoma in situ or who have clinically significant depression, renal, hepatic, cardiovascular, respiratory, metabolic, ophthalmologic, cerebrovascular, or other serious physical disease. - Participants in whom gastrointestinal stimulation might be dangerous, i.e. gastrointestinal hemorrhage or mechanical obstruction or perforation - Participants who have a known allergy or other intolerability to domperidone. - Participants with serum potassium, sodium, magnesium or calcium levels outside the normal range, serum creatinine > 6 mg/100 ml or > 0.6 mmol/l), or who have any other condition or situation that in the opinion of the investigator would either put the patient at risk of worsening health if enrolled in the trial or would prevent completion of the trial. - Participants who are concurrently participating in any therapeutic clinical trial. |
Country | Name | City | State |
---|---|---|---|
Canada | Calgary MS Clinic at Foothills Medical Centre | Calgary | Alberta |
Lead Sponsor | Collaborator |
---|---|
University of Calgary | Alberta Innovates Health Solutions |
Canada,
Alonso-Ortiz E, Levesque IR, Pike GB. MRI-based myelin water imaging: A technical review. Magn Reson Med. 2015 Jan;73(1):70-81. doi: 10.1002/mrm.25198. Epub 2014 Mar 6. Review. — View Citation
Bagnato F, Jeffries N, Richert ND, Stone RD, Ohayon JM, McFarland HF, Frank JA. Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years. Brain. 2003 Aug;126(Pt 8):1782-9. Epub 2003 Jun 23. — View Citation
Barkhof F, Bruck W, De Groot CJ, Bergers E, Hulshof S, Geurts J, Polman CH, van der Valk P. Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance. Arch Neurol. 2003 Aug;60(8):1073-81. — View Citation
Barkhof F, Calabresi PA, Miller DH, Reingold SC. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol. 2009 May;5(5):256-66. doi: 10.1038/nrneurol.2009.41. Review. — View Citation
Bernini GP, Lucarini AR, Franchi F, Salvetti A. Humoral effects of metoclopramide and domperidone in normal subjects and in hypertensive patients. J Endocrinol Invest. 1988 Nov;11(10):711-6. — View Citation
Bjartmar C, Kidd G, Mörk S, Rudick R, Trapp BD. Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol. 2000 Dec;48(6):893-901. — View Citation
Chandran S, Hunt D, Joannides A, Zhao C, Compston A, Franklin RJ. Myelin repair: the role of stem and precursor cells in multiple sclerosis. Philos Trans R Soc Lond B Biol Sci. 2008 Jan 12;363(1489):171-83. Review. — View Citation
Filippi M, Rovaris M, Rocca MA, Sormani MP, Wolinsky JS, Comi G; Eurpoean/Canadian Glatiramer Acetate Study Group. Glatiramer acetate reduces the proportion of new MS lesions evolving into "black holes". Neurology. 2001 Aug 28;57(4):731-3. — View Citation
Franklin RJ. Why does remyelination fail in multiple sclerosis? Nat Rev Neurosci. 2002 Sep;3(9):705-14. Review. — View Citation
Gregg C, Shikar V, Larsen P, Mak G, Chojnacki A, Yong VW, Weiss S. White matter plasticity and enhanced remyelination in the maternal CNS. J Neurosci. 2007 Feb 21;27(8):1812-23. — View Citation
Knoppert DC, Page A, Warren J, Seabrook JA, Carr M, Angelini M, Killick D, Dasilva OP. The effect of two different domperidone doses on maternal milk production. J Hum Lact. 2013 Feb;29(1):38-44. doi: 10.1177/0890334412438961. Epub 2012 May 3. — View Citation
Lublin FD, Baier M, Cutter G. Effect of relapses on development of residual deficit in multiple sclerosis. Neurology. 2003 Dec 9;61(11):1528-32. — View Citation
Mallik S, Samson RS, Wheeler-Kingshott CA, Miller DH. Imaging outcomes for trials of remyelination in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2014 Dec;85(12):1396-404. doi: 10.1136/jnnp-2014-307650. Epub 2014 Apr 25. Review. — View Citation
Metz LM, Zhang Y, Yeung M, Patry DG, Bell RB, Stoian CA, Yong VW, Patten SB, Duquette P, Antel JP, Mitchell JR. Minocycline reduces gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis. Ann Neurol. 2004 May;55(5):756. — View Citation
Mi S, Pepinsky RB, Cadavid D. Blocking LINGO-1 as a therapy to promote CNS repair: from concept to the clinic. CNS Drugs. 2013 Jul;27(7):493-503. doi: 10.1007/s40263-013-0068-8. Review. — View Citation
Nerozzi D, Magnani A, Dastoli C, Ferri E, Capesciotti G, Antonozzi I, Frajese G, Meltzer HY. Prolactin responses to domperidone in chronic schizophrenia. Psychiatry Res. 1992 May;42(2):159-69. — View Citation
Sloka S, Metz LM, Hader W, Starreveld Y, Yong VW. Reduction of microglial activity in a model of multiple sclerosis by dipyridamole. J Neuroinflammation. 2013 Jul 18;10:89. doi: 10.1186/1742-2094-10-89. — View Citation
Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998 Jan 29;338(5):278-85. — View Citation
Xiao L, Xu H, Zhang Y, Wei Z, He J, Jiang W, Li X, Dyck LE, Devon RM, Deng Y, Li XM. Quetiapine facilitates oligodendrocyte development and prevents mice from myelin breakdown and behavioral changes. Mol Psychiatry. 2008 Jul;13(7):697-708. Epub 2007 Aug 7. — View Citation
Zhao C, Fancy SP, Kotter MR, Li WW, Franklin RJ. Mechanisms of CNS remyelination--the key to therapeutic advances. J Neurol Sci. 2005 Jun 15;233(1-2):87-91. Review. — View Citation
* Note: There are 20 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Measures of repair within enhancing T1 MRI lesions | Texture analysis, Diffusion Tensor Imaging (DTI) and Magnetization Transfer Imaging (MTI) will be used. This is a pilot study so the investigators are measuring repair at 2 time points and with 3 imaging methods to aid in the design of future studies. | up to 32 weeks | |
Secondary | Number and type of adverse events over the 16 week treatment period. | Adverse events will be collected at all visits and by telephone if an encounter occurs. Clinical outcomes are not sufficiently sensitive or specific to stand as measures of repair in phase 2 clinical trials that aim to screen therapies for their potential to provide neuroprotection or enhance repair. Therefore the investigators will only use clinical measures at the baseline visit to describe participants with regards to level of clinical impairment. The investigators will use the standard measure of clinical impairment, the EDSS. The baseline neurological examination and EDSS will also be used to confirm the occurrence of a relapse. A relapse that occurs during the treatment period in a participant on domperidone will be considered an adverse event. Enhancing lesions on MRI after baseline will also be considered adverse events. | at 6 and 16 weeks | |
Secondary | Serum Prolactin Levels at both 6 and 16 weeks | To determine how much domperidone 10mg three times daily increases serum prolactin levels in this MS population over time. The investigators will also explore the relationship between prolactin level and repair. | at 6 and 16 weeks |
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