Clinical Importance of Glucose Regulation in Relapsing MS

NCT03004079 | Unknown

• 1 other identifier: 19259
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the relationship of blood glucose levels in persons with Multiple Sclerosis (MS) who have experienced a relapse and will be receiving intravenous steroids for the relapse, to their recovery from the relapse. Steroid exposure commonly leads to elevated serum blood glucose, however, standardized monitoring of blood glucose levels in the outpatient setting is not common. The clinical impact of any associated elevated blood glucose during steroid administration is unknown. We hypothesize that the blood glucose response to steroid treatment is clinically relevant to the MS-relapse recovery.

Conditions

Relapsing Remitting Multiple Sclerosis; Clinically Isolated Syndrome

Outcome Measures

Primary Outcomes (2)

• Relapse Recovery & Hyperglycemia

  Determine the relationship between mean postprandial blood glucoses (BG) and relapse recovery (complete vs. incomplete) following a standardized IVMP treatment.

  Recovery from relapse at 6-months

• Insulin Resistance & Relapse Severity

  Determine if insulin resistance (IR), measured by the Matsuda Index, is an independent predictor of relapse severity.

  At Baseline

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Adults aged 18-54 (inclusive) with a diagnosis of clinically isolated syndrome or relapsing remitting multiple sclerosis with an acute attack (relapse).

You may qualify if:

• Ability to provide informed consent
• Age 18 -59 years (inclusive)
• Ability to walk continuously for 6 minutes (per patient report)
• Clinically Isolated Syndrome (CIS) or Relapsing Remitting MS (RRMS) confirmed diagnosis by McDonald 2010 criteria
• Current MS relapse with objective findings on exam
• Relapse symptom onset within 2-weeks of screening
• Functional System Scores obtainable from a clinic visit within 6 months of the relapse assessment visit
• EDSS \< 6.5 at time of screening visit
• Inpatient, outpatient, emergency department, or inpatient observation status

You may not qualify if:

• Prior steroid exposure within 90 days of enrollment
• HgA1c ≥ 6.5 at baseline screening
• Evidence of concurrent infection
• Known contraindications to IV steroid treatment
• History of diabetes mellitus ( type 1 or 2) or severe hypertension
• Use of any glucose-regulating medications
• Pregnancy or current use of hormone replacement therapy

Sponsors & Collaborators

• University of Virginia: lead
• National Multiple Sclerosis Society: collaborator

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

Related Publications (47)

• Nickerson M, Marrie RA. The multiple sclerosis relapse experience: patient-reported outcomes from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. BMC Neurol. 2013 Sep 10;13:119. doi: 10.1186/1471-2377-13-119.

  PMID: 24016260 BACKGROUND

• Hirst C, Ingram G, Pearson O, Pickersgill T, Scolding N, Robertson N. Contribution of relapses to disability in multiple sclerosis. J Neurol. 2008 Feb;255(2):280-7. doi: 10.1007/s00415-008-0743-8. Epub 2008 Jan 23.

  PMID: 18204919 BACKGROUND

• 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. doi: 10.1212/01.wnl.0000096175.39831.21.

  PMID: 14663037 BACKGROUND

• Kwon S, Hermayer KL, Hermayer K. Glucocorticoid-induced hyperglycemia. Am J Med Sci. 2013 Apr;345(4):274-277. doi: 10.1097/MAJ.0b013e31828a6a01.

  PMID: 23531958 BACKGROUND

• Johnston KC, Hall CE, Kissela BM, Bleck TP, Conaway MR; GRASP Investigators. Glucose Regulation in Acute Stroke Patients (GRASP) trial: a randomized pilot trial. Stroke. 2009 Dec;40(12):3804-9. doi: 10.1161/STROKEAHA.109.561498. Epub 2009 Oct 15.

  PMID: 19834016 BACKGROUND

• Baker L, Juneja R, Bruno A. Management of hyperglycemia in acute ischemic stroke. Curr Treat Options Neurol. 2011 Dec;13(6):616-28. doi: 10.1007/s11940-011-0143-8.

  PMID: 21861124 BACKGROUND

• Southerland AM, Johnston KC. Considering hyperglycemia and thrombolysis in the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial. Ann N Y Acad Sci. 2012 Sep;1268(1):72-8. doi: 10.1111/j.1749-6632.2012.06731.x.

  PMID: 22994224 BACKGROUND

• Bruno A, Biller J, Adams HP Jr, Clarke WR, Woolson RF, Williams LS, Hansen MD. Acute blood glucose level and outcome from ischemic stroke. Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. Neurology. 1999 Jan 15;52(2):280-4. doi: 10.1212/wnl.52.2.280.

  PMID: 9932944 BACKGROUND

• Fang Y, Zhang S, Wu B, Liu M. Hyperglycaemia in acute lacunar stroke: a Chinese hospital-based study. Diab Vasc Dis Res. 2013 May;10(3):216-21. doi: 10.1177/1479164112459663. Epub 2012 Oct 18.

  PMID: 23079541 BACKGROUND

• Matute C, Domercq M, Perez-Samartin A, Ransom BR. Protecting white matter from stroke injury. Stroke. 2013 Apr;44(4):1204-11. doi: 10.1161/STROKEAHA.112.658328. Epub 2012 Dec 4. No abstract available.

  PMID: 23212168 BACKGROUND

• Wens I, Dalgas U, Deckx N, Cools N, Eijnde BO. Does multiple sclerosis affect glucose tolerance? Mult Scler. 2014 Aug;20(9):1273-6. doi: 10.1177/1352458513515957. Epub 2013 Dec 17.

  PMID: 24347183 BACKGROUND

• Sternberg Z, Leung C, Sternberg D, Li F, Karmon Y, Chadha K, Levy E. The prevalence of the classical and non-classical cardiovascular risk factors in multiple sclerosis patients. CNS Neurol Disord Drug Targets. 2013 Feb 1;12(1):104-11. doi: 10.2174/1871527311312010016.

  PMID: 23244431 BACKGROUND

• Marrie RA, Rudick R, Horwitz R, Cutter G, Tyry T, Campagnolo D, Vollmer T. Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurology. 2010 Mar 30;74(13):1041-7. doi: 10.1212/WNL.0b013e3181d6b125.

  PMID: 20350978 BACKGROUND

• Marrie RA, Horwitz R, Cutter G, Tyry T, Campagnolo D, Vollmer T. Comorbidity delays diagnosis and increases disability at diagnosis in MS. Neurology. 2009 Jan 13;72(2):117-24. doi: 10.1212/01.wnl.0000333252.78173.5f. Epub 2008 Oct 29.

  PMID: 18971448 BACKGROUND

• Sellebjerg F, Frederiksen JL, Nielsen PM, Olesen J. Double-blind, randomized, placebo-controlled study of oral, high-dose methylprednisolone in attacks of MS. Neurology. 1998 Aug;51(2):529-34. doi: 10.1212/wnl.51.2.529.

  PMID: 9710030 BACKGROUND

• Eriksson M, Andersen O, Runmarker B. Long-term follow up of patients with clinically isolated syndromes, relapsing-remitting and secondary progressive multiple sclerosis. Mult Scler. 2003 Jun;9(3):260-74. doi: 10.1191/1352458503ms914oa.

  PMID: 12814173 BACKGROUND

• Langer-Gould A, Popat RA, Huang SM, Cobb K, Fontoura P, Gould MK, Nelson LM. Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis: a systematic review. Arch Neurol. 2006 Dec;63(12):1686-91. doi: 10.1001/archneur.63.12.1686.

  PMID: 17172607 BACKGROUND

• Marrie RA, Horwitz R, Cutter G, Tyry T. Cumulative impact of comorbidity on quality of life in MS. Acta Neurol Scand. 2012 Mar;125(3):180-6. doi: 10.1111/j.1600-0404.2011.01526.x. Epub 2011 May 26.

  PMID: 21615355 BACKGROUND

• Godoy DA, Di Napoli M, Rabinstein AA. Treating hyperglycemia in neurocritical patients: benefits and perils. Neurocrit Care. 2010 Dec;13(3):425-38. doi: 10.1007/s12028-010-9404-8.

  PMID: 20652767 BACKGROUND

• Sala F, Menna G, Bricolo A, Young W. Role of glycemia in acute spinal cord injury. Data from a rat experimental model and clinical experience. Ann N Y Acad Sci. 1999;890:133-54. doi: 10.1111/j.1749-6632.1999.tb07989.x.

  PMID: 10668421 BACKGROUND

• Zhao QJ, Zhang XG, Wang LX. Mild hypothermia therapy reduces blood glucose and lactate and improves neurologic outcomes in patients with severe traumatic brain injury. J Crit Care. 2011 Jun;26(3):311-5. doi: 10.1016/j.jcrc.2010.08.014. Epub 2010 Oct 2.

  PMID: 20889287 BACKGROUND

• Selwyn R, Hockenbury N, Jaiswal S, Mathur S, Armstrong RC, Byrnes KR. Mild traumatic brain injury results in depressed cerebral glucose uptake: An (18)FDG PET study. J Neurotrauma. 2013 Dec 1;30(23):1943-53. doi: 10.1089/neu.2013.2928. Epub 2013 Oct 2.

  PMID: 23829400 BACKGROUND

• Johnston KC, Connors AF Jr, Wagner DP, Knaus WA, Wang X, Haley EC Jr. A predictive risk model for outcomes of ischemic stroke. Stroke. 2000 Feb;31(2):448-55. doi: 10.1161/01.str.31.2.448.

  PMID: 10657421 BACKGROUND

• Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, Brott T, Frankel M, Grotta JC, Haley EC Jr, Kwiatkowski T, Levine SR, Lewandowski C, Lu M, Lyden P, Marler JR, Patel S, Tilley BC, Albers G, Bluhmki E, Wilhelm M, Hamilton S; ATLANTIS Trials Investigators; ECASS Trials Investigators; NINDS rt-PA Study Group Investigators. Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet. 2004 Mar 6;363(9411):768-74. doi: 10.1016/S0140-6736(04)15692-4.

  PMID: 15016487 BACKGROUND

• Vespa P, McArthur DL, Stein N, Huang SC, Shao W, Filippou M, Etchepare M, Glenn T, Hovda DA. Tight glycemic control increases metabolic distress in traumatic brain injury: a randomized controlled within-subjects trial. Crit Care Med. 2012 Jun;40(6):1923-9. doi: 10.1097/CCM.0b013e31824e0fcc.

  PMID: 22610193 BACKGROUND

• Moro N, Ghavim S, Harris NG, Hovda DA, Sutton RL. Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury. Brain Res. 2013 Oct 16;1535:124-36. doi: 10.1016/j.brainres.2013.08.044. Epub 2013 Aug 29.

  PMID: 23994447 BACKGROUND

• Nijland PG, Michailidou I, Witte ME, Mizee MR, van der Pol SM, van Het Hof B, Reijerkerk A, Pellerin L, van der Valk P, de Vries HE, van Horssen J. Cellular distribution of glucose and monocarboxylate transporters in human brain white matter and multiple sclerosis lesions. Glia. 2014 Jul;62(7):1125-41. doi: 10.1002/glia.22667. Epub 2014 Apr 1.

  PMID: 24692237 BACKGROUND

• Bruno A, Kent TA, Coull BM, Shankar RR, Saha C, Becker KJ, Kissela BM, Williams LS. Treatment of hyperglycemia in ischemic stroke (THIS): a randomized pilot trial. Stroke. 2008 Feb;39(2):384-9. doi: 10.1161/STROKEAHA.107.493544. Epub 2007 Dec 20.

  PMID: 18096840 BACKGROUND

• Pulsinelli WA, Levy DE, Sigsbee B, Scherer P, Plum F. Increased damage after ischemic stroke in patients with hyperglycemia with or without established diabetes mellitus. Am J Med. 1983 Apr;74(4):540-4. doi: 10.1016/0002-9343(83)91007-0.

  PMID: 6837584 BACKGROUND

• Lassmann H. Hypoxia-like tissue injury as a component of multiple sclerosis lesions. J Neurol Sci. 2003 Feb 15;206(2):187-91. doi: 10.1016/s0022-510x(02)00421-5.

  PMID: 12559509 BACKGROUND

• Zivadinov R, Rudick RA, De Masi R, Nasuelli D, Ukmar M, Pozzi-Mucelli RS, Grop A, Cazzato G, Zorzon M. Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS. Neurology. 2001 Oct 9;57(7):1239-47. doi: 10.1212/wnl.57.7.1239.

  PMID: 11591843 BACKGROUND

• Viardot A, Grey ST, Mackay F, Chisholm D. Potential antiinflammatory role of insulin via the preferential polarization of effector T cells toward a T helper 2 phenotype. Endocrinology. 2007 Jan;148(1):346-53. doi: 10.1210/en.2006-0686. Epub 2006 Sep 28.

  PMID: 17008395 BACKGROUND

• Wieser V, Moschen AR, Tilg H. Inflammation, cytokines and insulin resistance: a clinical perspective. Arch Immunol Ther Exp (Warsz). 2013 Apr;61(2):119-25. doi: 10.1007/s00005-012-0210-1. Epub 2013 Jan 10.

  PMID: 23307037 BACKGROUND

• Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006 Jul;116(7):1793-801. doi: 10.1172/JCI29069.

  PMID: 16823477 BACKGROUND

• Kallaur AP, Oliveira SR, Colado Simao AN, Delicato de Almeida ER, Kaminami Morimoto H, Lopes J, de Carvalho Jennings Pereira WL, Marques Andrade R, Muliterno Pelegrino L, Donizete Borelli S, Kaimen-Maciel DR, Reiche EM. Cytokine profile in relapsing-remitting multiple sclerosis patients and the association between progression and activity of the disease. Mol Med Rep. 2013 Mar;7(3):1010-20. doi: 10.3892/mmr.2013.1256. Epub 2013 Jan 2.

  PMID: 23292766 BACKGROUND

• Rudick RA, Ransohoff RM. Cytokine secretion by multiple sclerosis monocytes. Relationship to disease activity. Arch Neurol. 1992 Mar;49(3):265-70. doi: 10.1001/archneur.1992.00530270079022.

  PMID: 1536629 BACKGROUND

• Khalili M, Azimi A, Izadi V, Eghtesadi S, Mirshafiey A, Sahraian MA, Motevalian A, Norouzi A, Sanoobar M, Eskandari G, Farhoudi M, Amani F. Does lipoic acid consumption affect the cytokine profile in multiple sclerosis patients: a double-blind, placebo-controlled, randomized clinical trial. Neuroimmunomodulation. 2014;21(6):291-6. doi: 10.1159/000356145. Epub 2014 May 6.

  PMID: 24821457 BACKGROUND

• Imitola J, Chitnis T, Khoury SJ. Cytokines in multiple sclerosis: from bench to bedside. Pharmacol Ther. 2005 May;106(2):163-77. doi: 10.1016/j.pharmthera.2004.11.007. Epub 2005 Jan 11.

  PMID: 15866318 BACKGROUND

• Schneider A, Long SA, Cerosaletti K, Ni CT, Samuels P, Kita M, Buckner JH. In active relapsing-remitting multiple sclerosis, effector T cell resistance to adaptive T(regs) involves IL-6-mediated signaling. Sci Transl Med. 2013 Jan 30;5(170):170ra15. doi: 10.1126/scitranslmed.3004970.

  PMID: 23363979 BACKGROUND

• Warabi Y. Role of IL-1 and potential therapies in multiple sclerosis. Drug Discovery Today: Therapeutic Strategies 2007;4:19-24.

  BACKGROUND

• Juhler M. Simultaneous determination of regional cerebral blood flow, glucose metabolism, and pH in acute experimental allergic encephalomyelitis. J Cereb Blood Flow Metab. 1987 Oct;7(5):578-84. doi: 10.1038/jcbfm.1987.108.

  PMID: 3654798 BACKGROUND

• Juhler M. Pathophysiological aspects of acute experimental allergic encephalomyelitis. Acta Neurol Scand Suppl. 1988;119:1-21. doi: 10.1111/j.1600-0404.1988.tb08016.x.

  PMID: 3064529 BACKGROUND

• JONES HH, JONES HH Jr, BUNCH LD. Biochemical studies in multiple sclerosis. Ann Intern Med. 1950 Oct;33(4):831-40. doi: 10.7326/0003-4819-33-4-831. No abstract available.

  PMID: 14771754 BACKGROUND

• Sternberg Z, Leung C, Sternberg D, Yu J, Hojnacki D. Disease modifying therapies modulate cardiovascular risk factors in patients with multiple sclerosis. Cardiovasc Ther. 2014 Apr;32(2):33-9. doi: 10.1111/1755-5922.12049.

  PMID: 24119301 BACKGROUND

• Mowry EM, Pesic M, Grimes B, Deen S, Bacchetti P, Waubant E. Demyelinating events in early multiple sclerosis have inherent severity and recovery. Neurology. 2009 Feb 17;72(7):602-8. doi: 10.1212/01.wnl.0000342458.39625.91.

  PMID: 19221292 BACKGROUND

• Penesova A, Vlcek M, Imrich R, Vernerova L, Marko A, Meskova M, Grunnerova L, Turcani P, Jezova D, Kollar B. Hyperinsulinemia in newly diagnosed patients with multiple sclerosis. Metab Brain Dis. 2015 Aug;30(4):895-901. doi: 10.1007/s11011-015-9665-1. Epub 2015 Mar 27.

  PMID: 25809135 BACKGROUND

• SCHUMACHER GA, BEEBE G, KIBLER RF, KURLAND LT, KURTZKE JF, MCDOWELL F, NAGLER B, SIBLEY WA, TOURTELLOTTE WW, WILLMON TL. PROBLEMS OF EXPERIMENTAL TRIALS OF THERAPY IN MULTIPLE SCLEROSIS: REPORT BY THE PANEL ON THE EVALUATION OF EXPERIMENTAL TRIALS OF THERAPY IN MULTIPLE SCLEROSIS. Ann N Y Acad Sci. 1965 Mar 31;122:552-68. doi: 10.1111/j.1749-6632.1965.tb20235.x. No abstract available.

  PMID: 14313512 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Myla Goldman, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Myla Goldman, MD

CONTACT

434-243-6069

Rachael Coleman, MPH

CONTACT

434-297-4102; rcoleman@virginia.edu

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of the Department of Neurology

Study Record Dates

• First Submitted: November 2, 2016
• First Posted: December 28, 2016
• Study Start: October 1, 2016
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2020
• Last Updated: November 7, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)