Polymorphisms of Interleukins, Glypican, and Human Leukocyte Antigen Genes and Treatment Response in Multiple Sclerosis. (WESTEMDRB1)

Association of Polymorphisms of the Interleukin-7 Receptor-α (IL-7R), Glypican 5 (GPC5), Interleukin-2 Receptor-α (IL2-RA) , Human Leukocyte Antigen Class II Beta Chain (HLA-DRB1) Genes and Treatment Response in Multiple Sclerosis (MS).

HLA-DRB1 * Gene and some genes involved in inflammation and immunity (IL-7R, GPC5, CTSS) have been linked to risk of MS and the response to treatment with immunomodulators. This research aims to estimate the risk that confers some variations in the sequence of these genes.

Study Overview

• Status: Unknown
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Genetic: Polymorphism of Interleukins, Glypican, and Human Leukocyte Antigen Genes.

Detailed Description

Genes HLA-DRB1 * and some genes involved in inflammation and immunity have been linked to risk of MS and the response to treatment with immunomodulators.

The HLA-DRB1 * genes have been associated with risk and response to treatment in MS in multiple studies; however, other genes have been controversial. This research aims to estimate the risk for MS that confers some variations in the sequence of IL-7R, GPC5, CTSS, HLA-DRB1 genes. Furthermore, it seeks to determine whether these gene variants (polymorphisms) are associated with treatment response to immunomodulators.

Subjects with MS and healthy subjects will be taken to assess the risk for MS. Besides the investigators obtain the medical history of relapse to assess response to treatment in accordance with Expanded Disability Status Scale (EDSS) and relapses.

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Recruiting
      • Instituto Jalisciense de Cancerologia
      • Contact: JOSE A. CRUZ RAMOS, PhD; Phone Number: 0152 3314886313; Email: josealfonsocr@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Subjects with multiple sclerosis and healthy subjects were studied. In subjects with multiple sclerosis, the number of relapses and EDSS was evaluated for two years.

Description

Inclusion Criteria for Cases:

• Subjects with multiple sclerosis
• 18 and over
• EDSS less than 5
• Signed informed consent

Inclusion Criteria for Controls:

• Healthy subjects
• 18 and over
• Signed informed consent

Exclusion Criteria for Cases:

• Mental retardation
• Withdrawal of consent
• No immunomodulatory treatment

Exclusion Criteria for Controls:

• Mental retardation
• Withdrawal of consent

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cases; Subjects with Relapsing-Remitting Multiple Sclerosis. Polymorphisms frequencies of Interleukins, Glypican, and Human Leukocyte Antigen Genes are determined.	Genetic: Polymorphism of Interleukins, Glypican, and Human Leukocyte Antigen Genes.; The frequencies of the polymorphic variants in subjects with MS and healthy subjects were evaluated. Also in subjects with MS, the response to treatment with the number of relapses and EDSS was assessed; to compare the allele frequencies of SNPs of Interleukins, Glypican, and Human Leukocyte Antigen Genes, between responders and no responders MS patients.
Controls; Healthy subjects. Polymorphisms frequencies of Interleukins, Glypican, and Human Leukocyte Antigen Genes are determined.	Genetic: Polymorphism of Interleukins, Glypican, and Human Leukocyte Antigen Genes.; The frequencies of the polymorphic variants in subjects with MS and healthy subjects were evaluated. Also in subjects with MS, the response to treatment with the number of relapses and EDSS was assessed; to compare the allele frequencies of SNPs of Interleukins, Glypican, and Human Leukocyte Antigen Genes, between responders and no responders MS patients.
Responders; Subjects with MS treated for at least two years that have less than one relapse per year or who had an increase of <1.5 points on the Expanded Disability Status Scale (EDSS) (if baseline EDSS was 0) or no increase in EDSS (baseline EDSS ≥1). Polymorphisms frequencies of Interleukins, Glypican, and Human Leukocyte Antigen Genes are determined.	Genetic: Polymorphism of Interleukins, Glypican, and Human Leukocyte Antigen Genes.; The frequencies of the polymorphic variants in subjects with MS and healthy subjects were evaluated. Also in subjects with MS, the response to treatment with the number of relapses and EDSS was assessed; to compare the allele frequencies of SNPs of Interleukins, Glypican, and Human Leukocyte Antigen Genes, between responders and no responders MS patients.
No responders; Subjects with MS that have more than one relapse per year treated for at least two years, and who had ≥1 relapse(s) or an increase of 1.5 points on the EDSS (if baseline EDSS was 0) or an increase of ≥0.5 points (baseline EDSS ≥1). Polymorphisms frequencies of Interleukins, Glypican, and Human Leukocyte Antigen Genes are determined.	Genetic: Polymorphism of Interleukins, Glypican, and Human Leukocyte Antigen Genes.; The frequencies of the polymorphic variants in subjects with MS and healthy subjects were evaluated. Also in subjects with MS, the response to treatment with the number of relapses and EDSS was assessed; to compare the allele frequencies of SNPs of Interleukins, Glypican, and Human Leukocyte Antigen Genes, between responders and no responders MS patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment response evaluated by relapses per year, evaluated during two years after recruitment.	Treatment response evaluated by relapses per year during two years after recruitment. The relapses are defined by any neurological sign or symptom that happens at least 30 days after any previous neurological deterioration episode began.	Two Years
Treatment response evaluated by Expanded Disability Status Scale (EDSS) during two years after recruitment.	Treatment response evaluated by Expanded Disability Status Scale (EDSS) during two years after recruitment. The EDSS scale ranges from 0 to 10; the increments are in 0.5. Scoring is based on an examination by a neurologist about the level of disability.	Two Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multiple Sclerosis Risk Conferred by Single Nucleotide Polymorphisms (SNPs) of Interleukins, Glypican, and Human Leukocyte Antigen Genes.	The risk conferred by SNPs of Interleukins, Glypican, and Human Leukocyte Antigen Genes: calculated by odds ratio when the allele frequencies of SNPs cases are compared with the allele frequencies of SNPs in healthy subjects.	One Year

Collaborators and Investigators

• Sponsor: Instituto Jalisciense de Cancerologia
• Collaborators: University of Guadalajara; Instituto Mexicano del Seguro Social
• Investigators: Principal Investigator: JOSE A. CRUZ RAMOS, PhD, Instituto Jalisciense de Cancerologia

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (ANTICIPATED): December 1, 2016
• Study Completion (ANTICIPATED): December 1, 2016

Study Registration Dates

• First Submitted: April 25, 2016
• First Submitted That Met QC Criteria: May 10, 2016
• First Posted (ESTIMATE): May 12, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): May 12, 2016
• Last Update Submitted That Met QC Criteria: May 10, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: EM-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED