Risk Factors in Early Multiple Sclerosis

NCT03586986 | Unknown

• 1 other identifier: 17-1884
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

The central hypothesis of this protocol is that it is possible, using First Degree Relatives (FDRs) of patients with Multiple Sclerosis (MS) and assessing a variety of both known and unknown risk factors for MS, to define a risk algorithm for earliest signs of development of MS. The plan will be to do an abbreviated brain Magnetic Resonance Imaging (MRI) scan in asymptomatic, young FDRs, analyze blood for a variety of immunological, genetic, neuroaxonal damage, metabolic, viral serology and other markers, and have FDRs fill out a detailed bioscreen questionnaire about lifestyle factors and perform a cognitive screening test. The investigators will then compare the results of the various blood/other studies in FDRs with and without an MRI showing signs signs concerning for MS, as well as age-and sex-matched NON-FDRs who will have blood drawn and fill out the questionnaire. With this preliminary cross-sectional study, the investigators hope to begin to identify a risk stratification model for those at highest risk of developing MS, ie FDRs, with a long-term goal of developing a longitudinal study to increase sensitivity and specificity of the risk model.

Conditions

Multiple Sclerosis; Magnetic Resonance Imaging; Biomarkers; Clinically Isolated Syndrome; Radiologically Isolated Syndrome

Keywords

First degree relative

Outcome Measures

Primary Outcomes (1)

• Discovery of Lesions disseminated in space on brain MRI

  Lesions disseminated in space on brain MRI. The presence or absence of these lesions will only be measured once at the initial visit.

  At the subject's Initial Visit

Secondary Outcomes (14)

• Define risk stratification algorithm for prediction of MS

  Within 4 months of the Initial Visit

• Define risk stratification algorithm for prediction of MS

  Within 4 months of the Initial Visit

• Define risk stratification algorithm for prediction of MS

  Within 4 months of the Initial Visit

• Define risk stratification algorithm for prediction of MS

  Within 4 months of the Initial Visit

• Define risk stratification algorithm for prediction of MS

  Within 4 months of the Initial Visit

Study Arms (3)

FDR with abnormal brain MRI

First degree relatives fulfilling lesions disseminated in space on MRI

Diagnostic Test: Brain MRI

FDR with normal brain MRI

First degree relatives not fulfilling lesions disseminated in space on MRI

Diagnostic Test: Brain MRI

Non-FDR

Age and sex-matched controls to FDRs noted above

Interventions

Brain MRI DIAGNOSTIC_TEST

Perform brain MRI; draw blood; fill out bioscreen questionnaire; perform SDMT

Also known as: Blood analysis, Bioscreen, Symbol Digit Modality Test (SDMT)

FDR with abnormal brain MRI; FDR with normal brain MRI

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The population will be a total of 300 women and men, of all races and ethnicities, between the ages of 18-30, inclusive, who have no symptoms of MS, but have at least one FDR with documented MS fulfilling McDonald 2017 criteria. FDRs with one or more siblings/parents with MS will be included, and more than one FDR of a proband MS patient will be allowed. A control group of age- and sex-matched controls who have no known family members with MS (out to first cousins and grandparents) will have blood drawn and fill out the environmental questionnaire, but will not undergo a brain/spine MRI. The controls will be matched 1:1:1 for those FDRs with positive MRI scans suggesting pre-symptomatic MS and those age-and sex-matched FDRs who do NOT have positive MRI scans suggesting pre-symptomatic MS.

You may qualify if:

• Male and female
• All races and ethnicities
• Ages 18-30
• Must have a parent, sibling or child with MS fulfilling McDonald 2017 criteria
• No symptoms suggestive of MS on formal screen
• Ability to undergo a non-contrast MRI and venipuncture, and perform an environmental screen, mood screen and cognitive test
• Male and female
• All races and ethnicities
• Ages 18-30
• Must NOT have a FDR (parent, sibling, child) or second degree relative (grandparent, aunt or uncle) with MS fulfilling McDonald 2017 criteria
• No symptoms suggestive of MS on formal screen
• Ability to undergo venipuncture and perform an environmental screen.

You may not qualify if:

• Symptoms suggestive of MS on formal screen
• Prior diagnosis of autoimmune disease that may be associated with CNS dysfunction and MRI lesions, e.g. Sjogren's
• Symptoms suggestive of MS on formal screen
• Prior diagnosis of autoimmune disease that may be associated with CNS dysfunction and MRI lesions, e.g. Sjogren's

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Colorado School of Public Health: collaborator

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Related Publications (19)

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  PMID: 24598783 BACKGROUND

• Rojas JI, Patrucco L, Miguez J, Besada C, Cristiano E. Brain atrophy in radiologically isolated syndromes. J Neuroimaging. 2015 Jan-Feb;25(1):68-71. doi: 10.1111/jon.12182. Epub 2014 Oct 13.

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• Disanto G, Barro C, Benkert P, Naegelin Y, Schadelin S, Giardiello A, Zecca C, Blennow K, Zetterberg H, Leppert D, Kappos L, Gobbi C, Kuhle J; Swiss Multiple Sclerosis Cohort Study Group. Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Ann Neurol. 2017 Jun;81(6):857-870. doi: 10.1002/ana.24954.

  PMID: 28512753 BACKGROUND

• Weinstock-Guttman B, Zivadinov R, Mahfooz N, Carl E, Drake A, Schneider J, Teter B, Hussein S, Mehta B, Weiskopf M, Durfee J, Bergsland N, Ramanathan M. Serum lipid profiles are associated with disability and MRI outcomes in multiple sclerosis. J Neuroinflammation. 2011 Oct 4;8:127. doi: 10.1186/1742-2094-8-127.

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• Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20;296(23):2832-8. doi: 10.1001/jama.296.23.2832.

  PMID: 17179460 BACKGROUND

• Salzer J, Hallmans G, Nystrom M, Stenlund H, Wadell G, Sundstrom P. Smoking as a risk factor for multiple sclerosis. Mult Scler. 2013 Jul;19(8):1022-7. doi: 10.1177/1352458512470862. Epub 2012 Dec 20.

  PMID: 23257617 BACKGROUND

• De Stefano N, Cocco E, Lai M, Battaglini M, Spissu A, Marchi P, Floris G, Mortilla M, Stromillo ML, Paolillo A, Federico A, Marrosu MG. Imaging brain damage in first-degree relatives of sporadic and familial multiple sclerosis. Ann Neurol. 2006 Apr;59(4):634-9. doi: 10.1002/ana.20767.

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• Gabelic T, Ramasamy DP, Weinstock-Guttman B, Hagemeier J, Kennedy C, Melia R, Hojnacki D, Ramanathan M, Zivadinov R. Prevalence of radiologically isolated syndrome and white matter signal abnormalities in healthy relatives of patients with multiple sclerosis. AJNR Am J Neuroradiol. 2014 Jan;35(1):106-12. doi: 10.3174/ajnr.A3653. Epub 2013 Jul 25.

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• Solomon AJ, Schindler MK, Howard DB, Watts R, Sati P, Nickerson JP, Reich DS. "Central vessel sign" on 3T FLAIR* MRI for the differentiation of multiple sclerosis from migraine. Ann Clin Transl Neurol. 2015 Dec 16;3(2):82-7. doi: 10.1002/acn3.273. eCollection 2016 Feb.

  PMID: 26900578 BACKGROUND

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  PMID: 24076602 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood drawn for SNP, HLA typing, and possible RNA analysis

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Hematologic Tests

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• John R Corboy, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John R Corboy, MD

CONTACT

303-724-2187; john.corboy@ucdenver.edu

Sydney Lipton, BA

CONTACT

sydney.lipton@cuanschutz.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2018
• First Posted: July 16, 2018
• Study Start: July 26, 2018
• Primary Completion: May 1, 2024
• Study Completion: May 1, 2024
• Last Updated: February 6, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)