Role of Simvastatin in Relapsing-Remitting Multiple Sclerosis
NCT ID: NCT04178980
Last Updated: 2019-11-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE1
60 participants
INTERVENTIONAL
2020-01-01
2022-03-01
Brief Summary
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Detailed Description
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Subtypes of MS are considered important not only for prognosis but also for treatment decisions and include:
* Relapsing remitting MS (RRMS)
* Primary progressive MS (PPMS)
* Secondary progressive MS (SPMS)
* Progressive relapsing MS (PRMS). RRMS is the most common subtype (approximately 87%) which characterized by unpredictable acute attacks followed by periods of remission . During RRMS, inflammatory attacks on myelin and nerve fibers occur. Activated immune cells cause lesions in the CNS which generate symptoms of visual impairments, tingling and numbness, episodic bouts of fatigue, intestinal and urinary system disorders, spasticity, and learning and memory impairment. Approximately 10-15% of MS patients are diagnosed with PPMS which largely affect the nerves of the spinal cord. PPMS patients tend to have fewer brain lesions. Induced symptoms include problems with walking, weakness, stiffness, and trouble with balance.
Nearly 65% of patients with RRMS will subsequently develop SPMS which is considered the second phase of this disease. Many individuals experience increased weakness, intestinal and urinary system disorders, fatigue, stiffness, mental disorders, and psychological impairment. Finally, PRMS is the least common type of MS that occurs in approximately 5% of patients and is associated with symptoms such as eye pain and double vision, along with sexual, intestinal and urinary system dysfunction, dizziness, and depression. Generally MS is detected between the ages of 20 and 40 years, but less than 1% can occur in childhood and approximately 2-10% after 50 years of age .
This pathologic condition affects women more than men (sex ratio 2.5:1) and the prevalence varies by geographic area, ranging from 120 per 100,000 individuals . The etiology of MS remains unclear, however it can be considered a multifactorial disease and include a genetic predisposition combined with environmental influences .
The initial treatment strategy for MS is largely based on disease-modifying drugs such as interferon-β and glatiramer acetate . The effects of these treatments are partially for symptomatic alleviation and do not stop the ongoing neurodegeneration.
Simvastatin Simvastatin belongs to a group of medicines called statins. Its action is inhibiting 3-hydroxy-3-methylglutaryl (HMG) coenzyme A reductase. HMG-CoA reductase, the rate-limiting enzyme of the HMG-CoA reductase pathway, the metabolic pathway responsible for the endogenous production of cholesterol. Statins are more effective than other lipid-regulating drugs at lowering LDL-cholesterol concentration Furthermore, simvastatin has pleiotropic effects associated with onset and progression of autoimmune and inflammatory diseases, cancer, neurodegenerative disorders, strokes, bacterial infections, and human immunodeficiency virus. Understanding these issues will improve the prognosis of patients who are administered statins and potentially expand our ability to treat a wide variety of diseases .
Simvastatin was found to decrease the incidence of hemodynamically significant rejection episodes in cardiac transplant patients. This effect was not significantly correlated to reduction in cholesterol levels in these patients. Subsequent studies have revealed many immunological pathways sensitive to modulation by statins:
1. Simvastatin inhibit interferon-γ-inducible class II transactivator (CIITA) to decrease the induction/up regulation of MHC class II molecules on professional \& non- professional antigen presenting cells.
2. Statins bind to β2 integrin and thereby block T-cell co-stimulation by means of lymphocyte function-associated antigen-1 (LFA-1).
3. In monocytes and macrophages, statins decrease chemotaxis, lipopolysaccharide (LPS) mediated release of tumour necrosis factor-α (TNF-α), activation of NO synthase8 and LPS-stimulated secretion of matrix metalloproteinase-9 (12).
Common simvastatin side effects may include:
* Headache;
* Constipation, nausea, stomach pain; or
* Cold symptoms such as stuffy nose, sneezing, sore throat.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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case
Simvastatin in relapsing remitting multiple sclerosis
Simvastatin use as adjuvant thearapy in relapsing remitting multiple sclerosis
control
Simvastatin in relapsing remitting multiple sclerosis
Simvastatin use as adjuvant thearapy in relapsing remitting multiple sclerosis
Interventions
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Simvastatin in relapsing remitting multiple sclerosis
Simvastatin use as adjuvant thearapy in relapsing remitting multiple sclerosis
Eligibility Criteria
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Inclusion Criteria
2\. EDSS up to 4. 3. Males and Females aged 18 to 65 4. pregnancy test within 7 days prior to being registered/randomized. Participants are considered not of child bearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
5\. Willing and able to comply with the trial protocol (e.g. can tolerate MRI and fullfills the requirements for MRI, e.g. not fitted with pacemakers or permanent hearing aids), with ability to understand and complete questionnaires 6. Willing and able to provide written informed consent
Exclusion Criteria
4\. Active Hepatic disease or known severe renal failure (creatinine clearance \<30ml/min) 5. Screening levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatine kinase (CK) are three times the upper limit of normal patients.
6\. Patient unable to tolerate or unsuitable to have baseline MRI scan (e.g. metal implants, heart pacemaker) or MRI scan not of adequate quality for analysis (e.g. too much movement artefact).
7\. Females who are pregnant, planning pregnancy or breastfeeding. 8. Allergy to simvastatin
18 Years
65 Years
ALL
No
Sponsors
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Assiut University
OTHER
Responsible Party
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Mena Mahfouz Fahim
researcher
Central Contacts
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References
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Loma I, Heyman R. Multiple sclerosis: pathogenesis and treatment. Curr Neuropharmacol. 2011 Sep;9(3):409-16. doi: 10.2174/157015911796557911.
Gadoth N. Multiple sclerosis in children. Brain Dev. 2003 Jun;25(4):229-32. doi: 10.1016/s0387-7604(03)00035-4.
Boiko A, Vorobeychik G, Paty D, Devonshire V, Sadovnick D; University of British Columbia MS Clinic Neurologists. Early onset multiple sclerosis: a longitudinal study. Neurology. 2002 Oct 8;59(7):1006-10. doi: 10.1212/wnl.59.7.1006.
Haas J, Korporal M, Balint B, Fritzsching B, Schwarz A, Wildemann B. Glatiramer acetate improves regulatory T-cell function by expansion of naive CD4(+)CD25(+)FOXP3(+)CD31(+) T-cells in patients with multiple sclerosis. J Neuroimmunol. 2009 Nov 30;216(1-2):113-7. doi: 10.1016/j.jneuroim.2009.06.011. Epub 2009 Jul 31.
Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech WF. Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clin Infect Dis. 1994 Jan;18 Suppl 1:S79-83. doi: 10.1093/clinids/18.supplement_1.s79.
Other Identifiers
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simvastatin in MS
Identifier Type: -
Identifier Source: org_study_id