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Without the participation of people with MS, it would be impossible to develop new and better therapies and other interventions.

Therapeutic Monitoring of Drugs Used in the Treatment of Multiple Sclerosis

Study Purpose

The main goal of multiple sclerosis (MS) treatment is to prevent further relapses of the disease and the progression of neurological deficit. Although MS cannot yet be cured, early control of symptoms and reduction of disease progression is associated with a longer time to disability and improve long-term treatment outcomes. Currently, MS is treated using a multidisciplinary approach, which consists of treatment with so-called "disease-modifying drugs" ("DMDs"), symptomatic therapy of individual symptoms, lifestyle adjustments, psychological support, and rehabilitation interventions. According to the latest results, treatment with "DMDs" can reduce the annual incidence of relapses by 29-68% compared to placebo or an active comparator. Thus, as can be seen, even this group of modern drugs does not completely compensate for MS in many patients. For this reason, there is a need to use certain parameters to best assess the effectiveness of individual treatments in specific patients with MS in routine clinical practice. Therapeutic drug monitoring (TDM) is a specific method of clinical pharmacology that has long been used to monitor therapy for a variety of diseases by measuring drug concentrations in body fluids (plasma, serum, whole blood, cerebrospinal fluid, breast milk) with subsequent interpretation by clinical pharmacologist and acceptance by the clinician. The groups of drugs for which TDM is routinely performed include selected groups of antibiotics (aminoglycosides, vancomycin, beta-lactams), immunosuppressants, digoxin, and especially drugs used in neurology and psychiatry (antiepileptics and psychotropic drugs). As far as "DMDs" is concerned, the first data on the possibility of using TDM in the therapy of MS have already appeared in the professional literature, but these are so far rare and completely insufficient. In addition, individual drugs differ not only in efficacy but also in dose, dosing schedule, and safety profile. The development of new analytical methods to determine serum or whole blood "DMDs" concentrations, together with the objectification of the relationship between measured concentrations to the patient's clinical condition and the possibility of objectifying patient adherence to treatment, could therefore significantly help individualize the dosage of "DMDs" in each individual patient.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- patients diagnosed with MS of all forms using any of the oral "DMDs" - men and women older than 18 years.

- signature of the Informed Consent to Participate in the Study.

Exclusion Criteria:

- minor patients (below 18 years of age) - refusal to sign the Informed Consent to Participate in the Study.

- refusal of blood samples taken beyond standard examinations.

Criteria for exclusion from the study.

- non-compliance with the treatment regimen according to the decision of the attending physician.

- non-participation in blood samples taken as part of standard examinations

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05112484
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University Hospital Ostrava
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Ivana Kacířová, Assoc. Prof.,MD,PhD
Principal Investigator Affiliation	University Hospital Ostrava
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries	Czechia
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Multiple Sclerosis
Study Website:	View Trial Website

Additional Details

The study group will consist of individuals with MS who will be indicated for some of the orally used disease-modifying drugs ("DMDs")

- fingolimod, dimethyl fumarate, cladribine, or teriflunomide, both patients with established treatment and patients who will have this medication newly used.

All medical care will be performed according to the habits and decisions of the attending physician depending on the clinical condition of the patient, in addition, only 3 blood tubes will be taken on the day of scheduled standard collection and 1 blood tube for the entire duration of the study for genetic testing. Of these, 2 tubes will be collected as part of a standard fasting sample from fasting before drug administration with other routinely collected blood samples (including one tube for the duration of the genetic testing study) and 1 tube will be collected 2-3 hours after drug administration. to determine the maximum drug concentration. For the patient, all the load will mean only one extra collection, ie a collection after taking the drug, either from a new injection or with an inserted cannula. Blood samples obtained from 2 tubes taken on an empty stomach will be used to determine the concentration of "DMDs" of the drug before use and to analyze other biomarkers that could be used to evaluate the patient's clinical condition, such as signs of axonal damage (plasma neuro-filament light chain

- pNfL).

"), Glial damage (so-called chitinase 3-like 1 -" CHI3L1 "), concentrations of selected cytokines or concentrations of CD4 + and CD8 + T cells. One tube of blood taken also on an empty stomach, once for the duration of the study, will be used for genetic testing of drug transporters such as P-gp (ABCB1) or BCRP (ABCG2). At the same time, the patient will perform the usual clinical examinations (physical assessment of the clinical condition, evaluation of the EDSS scale, monitoring of possible side effects of the medication used and the MSQOL-54 quality of life questionnaire) and once a year routine magnetic resonance imaging of the brain. The information thus obtained will be correlated with the achieved concentration of "DMDs" used to determine whether this group of drugs would be suitable for routine therapeutic monitoring, similar to antiepileptics, for which TDM has been part of routine clinical practice to optimize since the 1970s. pharmacotherapy in individual patients to compensate for the clinical condition with minimal side effects. The investigators would also try to establish a reference range of individual "DMDs", which would be defined as the concentration of drug in serum or whole blood at which most patients are expected to achieve an optimal clinical response. However, since some patients may (similarly to antiepileptics) require a concentration outside this reference range, the investigators would try to determine the so-called "individual therapeutic concentration" in these cases, i.e. the concentration at which MS without an MS attack with good tolerability of medication would be achieved, possibly as the best compromise between improving MS control and concentration-dependent side effects. For the patient, all loading will mean only one extra collection, i.e. a post-drug collection, which can be done either from a new injection or with an inserted cannula. This collection may involve common risks, such as bleeding from an injection site due to insufficient compression of the injection site, the development of a hematoma, or a drop in blood pressure. By obtaining the valuable parameters mentioned above, not only others, resp. future patients with MS, but due to the short duration of the study and at the same time the lifelong influence of the patient with multiple sclerosis, these results may help to optimize the pharmacotherapy of "DMDs" also in a specific individual patient

- study participant.

However, because long-term patient adherence to treatment is equally important for MS compensation, the introduction of TDM "DMDs" for attending physicians could help not only to optimize the pharmacotherapy of MS but also to control the patient's adherence to treatment.

Arms & Interventions

Arms

: Gilenya

Gilenya (fingolimod) - first registration 17 March 2011, last renewal 16 November 2020, selective immunosuppressant (ATC code L04AA27), sphingosine-1-phosphate receptor modulator

: Tecfidera

Tecfidera (dimethyl fumarate) - first registration 30 January 2014, last renewal 20 September 2018, cytostatic and immunomodulatory drug (ATC code L04AX07), an activator of the transcription pathway of nuclear factor Nrf2

: Mavenclad

Mavenclad (cladribine) - first registration 22/08/2017, selective immunosuppressant (ATC code L04AA40), nucleoside analogue of deoxyadenosine

: Aubagio

Aubagio (teriflunomide) - first registration on 26 August 2013, last renewal on 28 May 2018, selective immunosuppressant (ATC code L04AA31), an inhibitor of the mitochondrial enzyme dihydroorotate dehydrogenase

Interventions

Diagnostic Test: - Measurement of concentrations of orally-used DMDs

For effectiveness - the measured concentrations of orally used "DMDs" will be correlated with the clinical condition of patients with MS (usual clinical examinations such as physical assessment of clinical condition, evaluation of EDSS scale, MSQOL-54 quality of life questionnaire, and routine magnetic resonance imaging of the brain once a year). At the same time, the relationship between the measured concentrations of orally used "DMDs" and the concentrations of other biomarkers of MS, such as signs of axonal (so-called plasma neurofilament light chain - "pNfL") and glial (so-called chitinase 3-like 1 - "CHI3L1") damage, will be analyzed. concentrations of selected cytokines, concentrations of CD4 + and CD8 + T-lymphocytes, and the results of a genetic examination of drug transporters, again with an effect on the clinical condition of the patient.

Diagnostic Test: - Genetic testing

One blood tube will be taken for genetic testing for the duration of the study, again with standard and routine single injections before taking the drug.

Diagnostic Test: - Parameters for routine use of DMDs

For safety - the usual parameters for routine use of "DMDs" will be monitored (blood count, liver tests, renal function, etc. according to the specifics of individual drugs).

Other: - Side effects of orally used DMDs

For tolerability - possible side effects of orally used "DMDs" will be monitored and the effect of genetic testing of drug transporters will be analyzed.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.