Study on the relationship between genes and disease severity, disease burden and effectiveness of disease modifying medication in Dutch patients with Multiple Sclerosis

Study on the relationship between genes and disease severity, disease burden and effectiveness of disease modifying medication in Dutch patients with Multiple Sclerosis - GEMS study - Genetic Etiology of Multiple Sclerosis

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON45439

Enrollment

600

Registered

2017-03-14

Start date

2017-03-01

Completion date

Unknown

Last updated

2024-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

demyelinating disease multiple sclerosis

Interventions

disease burden

disease severity

genetic factors

multiple sclerosis

Eligibility

Age

18 Years to 64 Years

Inclusion criteria

Inclusion criteria: 600 Dutch patients with MS from six MS centres. We estimate that approximately 100 patients per centre will participate in the study, which is a feasible number of patients according to the neurologists of the respective centres.;In order to be eligible to participate in this study, subjects must meet all of the following criteria: - diagnosed with MS for at least one year - able and willing to participate in the study - Dutch and from caucasian origin - between 20 and 60 years of age;In addition, we are aiming for the gender distribution of our subjects to reflect the epidemiological findings for MS, i.e. approximately 35 % male and 65 % female subjects.

Exclusion criteria

Exclusion criteria: Not applicable.

Design outcomes

Primary

Measure	Time frame
Here, we first define the genotypic and phenotypic measurements. Subsequently, we will provide the parameter settings to perform the gene set analysis and PRS analysis that we will perform on the measured data. Genotypic/GWAS data For each patient we will establish, from the blood sample, a so-called genotype (one out of the two possible SNP variants) for the 550.000 SNPs on the GWAS chip. We will then use these genome-wide genotyping data and the collected phenotypic data to conduct a within case GWAS of disease severity, disease burden and the effectiveness of a number of selected DMTs for MS (see above). The resulting GWAS data will consist of a P value that indicates the likelihood of association between each of the 550.000 SNPs and each of the phenotypes Phenotypic data Using the outcomes of the online questionnaires (MSQoL-54, MSIP and General Assessment) and the neurological data (EDSS) we will derive the following phenotypic values for each patient: Neurologist-derived disease severity. The MS Severity Score (MSSS) can be obtained by referencing the EDSS and diseases duration (the time between disease onset and time of EDSS scoring) to the global MSSS Table (Roxburgh et al., 2005). The MSSS Table essentially ranks individuals from lowest EDSS to highest EDSS for a given disease duration, and expresses this as a decile rank between 0 (least affected) and 10 (most severely affected). The MSSS will be computed using the MSSS test software version 2.0 (Roxburgh et al., 2005). Patient-derived disease severity. The MSIP is a questionnaire to measure patient-reported severity of MS-related disability (Wynia et al., 2008). The MSIP consists of 36 items divided over seven scales and has four additional impairment items (symptoms). Item scores are graded on three to five-point rating scales with discrete responses, ranging from 0 (no disability) to 3 or 4 (complete disability). To assess patient-derived disease severity the respective sco	—

Measure

Time frame

Here, we first define the genotypic and phenotypic measurements. Subsequently, we will provide the parameter settings to perform the gene set analysis and PRS analysis that we will perform on the measured data. Genotypic/GWAS data For each patient we will establish, from the blood sample, a so-called genotype (one out of the two possible SNP variants) for the 550.000 SNPs on the GWAS chip. We will then use these genome-wide genotyping data and the collected phenotypic data to conduct a *within case* GWAS of disease severity, disease burden and the effectiveness of a number of selected DMTs for MS (see above). The resulting GWAS data will consist of a P value that indicates the likelihood of association between each of the 550.000 SNPs and each of the phenotypes Phenotypic data Using the outcomes of the online questionnaires (MSQoL-54, MSIP and General Assessment) and the neurological data (EDSS) we will derive the following phenotypic values for each patient: Neurologist-derived disease severity. The MS Severity Score (MSSS) can be obtained by referencing the EDSS and diseases duration (the time between disease onset and time of EDSS scoring) to the global MSSS Table (Roxburgh et al., 2005). The MSSS Table essentially ranks individuals from lowest EDSS to highest EDSS for a given disease duration, and expresses this as a decile rank between 0 (least affected) and 10 (most severely affected). The MSSS will be computed using the MSSS test software version 2.0 (Roxburgh et al., 2005). Patient-derived disease severity. The MSIP is a questionnaire to measure patient-reported severity of MS-related disability (Wynia et al., 2008). The MSIP consists of 36 items divided over seven scales and has four additional impairment items (symptoms). Item scores are graded on three to five-point rating scales with discrete responses, ranging from 0 (no disability) to 3 or 4 (complete disability). To assess patient-derived disease severity the respective sco

—

Secondary

Measure	Time frame
To answer our primary research question, we perform gene set analysis and PRS analysis on the phenotypic data which are continous variables. Here, to answer our secondary research question, we will perform the same analysis routines on the effectiveness of the selected DMTs (categorical data). These analysis have a more explorative nature, because it is currently difficult to estimate the medication use in this patient cohort.	—

Measure

Time frame

To answer our primary research question, we perform gene set analysis and PRS analysis on the phenotypic data which are continous variables. Here, to answer our secondary research question, we will perform the same analysis routines on the effectiveness of the selected DMTs (categorical data). These analysis have a more explorative nature, because it is currently difficult to estimate the medication use in this patient cohort.

—

Countries

The Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)