Improving the Effect of Multiple Sclerosis Drugs by Chronobiology

May 3, 2024 updated by: Hadassah Medical Organization

Improving the Effect of Dimethyl Fumarate and Diroximel Fumarate (DRF) for Patients With Multiple Sclerosis by Chronobiology

A trial for evaluating the ability to improve the effect of dimethyl fumarate in patients with Multiple Sclerosis (MS) by chronobiology A controlled-randomization dosing regimen administered to patients with MS and provided by a designated app. The treatment limitations of time interval is pre-defined according to approved therapeutic windows.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Dimethyl fumarate (DMF) is an oral option for patients with relapsing forms of MS. The effectiveness of DMF on the clinical and radiological activity of multiple sclerosis were demonstrated in a real-world setting, both in naive patients and in those switching from other multiple sclerosis therapies. Sustained safety and efficacy of DMF was observed in patients continuing on treatment for up to 11 years, supporting DMF as a long-term treatment option for patients with MS. It continues to be an efficacious treatment for multiple sclerosis with a favorable safety profile demonstrated over 10 years of clinical use Patients who have partial response or non-responders in most cases require different medications associated with a less favorable safety profile. Recently fda approved Diroximel fumarate (DRF) is a noval drug which is bioequivalent to DMF regarding efficacy and safety profiles, differing only by chemical precursor structure which is hypothesized to elicit less irritation in the GI tract than DMF. Both drug active metabolites are similar in bioactivity and efficacy treating MS Many aspects of cellular physiology display circadian (approximately 12-h) rhythms. Dysfunction of the circadian clock molecular circuitry is associated with human health derangements, including neurodegeneration, increased risk of cancer, cardiovascular diseases and the metabolic syndrome. Recent evidences support a link between the circadian clock circuitry and biological cycles in multiple systems. Regular dosing of therapy may lead to compensatory mechanisms and are associated with adaptation of the immune system that may prohibit a maximal clinical effect.

This open-label study will test the implementation of controlled randomization of time of administration of Dimethyl fumarate to patients with MS. Random changes in the time of administration and dosages of Dimethyl fumarate within pre-defined approved limits which are within the approved therapeutic window will be provided to patient by a designated cellular application. Patients will be followed for 12 weeks for clinical improvement using the Expanded Disability Status Scale (EDSS) and MRI.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Jerusalem, Israel
        • Hadassah Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age between 18-60 at the time of enrollment
  2. A diagnosis of MS and treatment with dimethyl fumarateDimethyl fumarate or Diroximel fumarate for at least 6 months
  3. Females of childbearing potential must be non-pregnant (as determined by a serum pregnancy test at enrollment) and agree to use adequate contraceptive means throughout the study.
  4. Patients must be able to adhere to the visit schedule and protocol requirements and be available to complete the study.
  5. Patients must satisfy a medical examiner about their fitness to participate in the study.
  6. Patients must provide written informed consent to participate in the study.

Exclusion Criteria:

  • 1. Active malignancy or any malignancy diagnosed in the last 5 years or previous diagnosis of hepatocellular carcinoma at any time.

    2. Known human deficiency virus (HIV) or Hepatitis virus infections. 3. The use of steroids, or other immunosuppression. 4. Participation in another clinical trial within 30 days prior to intervention.

    5. Patients with an inability to communicate well with the PI and staff (i.e., language problem, poor mental development or impaired cerebral function).

    6. Patients who will be unavailable for the duration of the trial, are likely to be noncompliant with the protocol, or who are felt to be unsuitable by the PI for any other reason.

    7. Any underlying medical condition that in the opinion of the study investigator impair the ability of the patient to complete the follow-up or to receive the planned treatment regimen

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Device Feasibility
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: patients using the app for dosing regimen
All of the enrolled patients will receive their dimethyl fumarate prescribed by their GP. During the 12 weeks' study period, patients in the intervention arm will receive the medication timed by the app- dose and time of administration will be determined using a designated app. The app will implement random changes in time of administration limited by a pre-defined range assigned by the therapeutic windows
Device: App randomizing dosing regimen
patients will receive their dimethyl fumarate treatment and the dose and time of administration will be determined using a designated app.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
safety assessment
Time Frame: 12 weeks
The primary outcome is to assess to assess the safety of incorporating controlled randomization to Dimethyl fumarate dosing regimen provided by an app in patients with MS. Safety will be assessed through clinical follow-up which will include history taking with emphasize on possible AE
12 weeks
assessment of AE
Time Frame: 12 weeks
physical examination and assessment by EDSS score
12 weeks
assessment of AE
Time Frame: 12 weeks
laboratory tests - detect changes in cbc for lymphopenia (below 1.03 10e9/L)
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hadassah Medical Organization

Investigators

  • Study Director: yoav hershkovtiz, md, Hadassah Medical Organization

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 8, 2022

Primary Completion (Actual)

June 1, 2023

Study Completion (Actual)

June 2, 2023

Study Registration Dates

First Submitted

April 17, 2024

First Submitted That Met QC Criteria

April 23, 2024

First Posted (Actual)

April 25, 2024

Study Record Updates

Last Update Posted (Actual)

May 6, 2024

Last Update Submitted That Met QC Criteria

May 3, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 170886-HMO-CTIL

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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