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.

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.

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