Improving the Treatment of Acute Relapses in Multiple Sclerosis Through Intranasal Methylprednisolone Administration (IN-DXM-EMRR)

Towards the Improvement of the Treatment of Acute Relapses in Multiple Sclerosis: A Randomized Double-blind, Non-inferiority Controlled Trial Comparing Intranasal Versus Intravenous Methylprednisolone

This Clinical Trial evaluates the nasal administration of Methylprednisolone as a treatment strategy for Acute Relapses in Multiple Sclerosis

Study Overview

• Status: Enrolling by invitation
• Conditions: Treatment; Multiple Sclerosis Relapsing Remitting
• Intervention / Treatment: Other: IV Methylprednisolone administration; Drug: Nasal Methylprednisolone (MT)

Detailed Description

This is a prospective, comparative, randomized, double-blind study adhered to the principles established by the Helsinki Declaration, including informed consent. Patients with a diagnosis of Relapsing-Remitting Multiple Sclerosis (RRMS) from the National Institute of Neurology and Neurosurgery (INNN) that are coursing with acute recurrency will be included. The recruited patients will be organized into two paired groups of 40 patients each, of which group 1 will receive 1g IV methylprednisolone, and group 2 will receive the intranasal dose equivalent to 1g of IV methylprednisolone. Clinical symptoms will be measured with the Expanded Disability Status Scale (EDSS) and data will be complemented with results of clinical tests, general laboratories and serum concentration of MP and inflammatory markers. Adverse effects in each group will also be identified and quantified. Statistical analysis: descriptive, assumption of normality, bivariate comparison of means and multivariate, in addition to intention to treat.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 14269
    • Instituto Nacional de Neurologia y Neurocirugia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age between 18 and 65 years.
• Diagnosis of RRMS with an evolution from diagnosis of 3 months to 10 years.
• Kurtzke Expanded Disability Status Scale (EDSS) from 1 to 6 (grade 6 includes patients with unilateral aid to ambulate)
• No contraindication for the administration of MP.
• Agree to participate in the study by means of a signed informed consent

Exclusion Criteria:

• Intake of anti-inflammatory steroids in the last 3 days.
• Patients with active bacterial, viral or fungal infections or undergoing treatment.
• Patients with hypertension.
• Patients with diabetes mellitus.
• Patients with hypo or hyperthyroidism.
• Patients with glaucoma.
• Patients with neoplasms.
• Diagnosis of systemic diseases such as: cardiovascular, pulmonary, hepatic, endocrine, gastrointestinal, etc.
• Patients with suspected or confirmed pregnancy by means of serum or urinary laboratory tests.
• Breastfeeding patients.
• Patients with a history of resistance to glucocorticoids.
• Patients with a history of severe adverse reactions to glucocorticoids.
• Patients with a history of hyposmia or anosmia.
• Patients diagnosed with active sinusitis.
• Patients with allergic rhinitis.
• Patients with upper respiratory tract infections.
• deviated septum
• History of nasal surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Intravenous Methylprednisolone treatment in relapsing-remittent multiple sclerosis; Intravenous methylprednisolone is the standard treatment for a multiple sclerosis relapse. Thus, 40 randomly enrolled patients aged 18-65 years with relapsing-remitting multiple sclerosis that assist to the hospital and confirmed with a relapse, will be treated with intravenous methylprednisolone, 1000 mg, once a day for 3 days for moderate relapses or 5 days for severe ones. A written informed consent will be obtained from each participant or a legal representative whenever the participant could not provide consent.	Other: IV Methylprednisolone administration; Group 1 will receive 1g methylprednisolone IV for 3 or 5 days, according to the severity of the relapse; Other Names: ST
Experimental: Intranasal Methylprednisolone administration in relapsing-remittent multiple sclerosis; Nasal Methylprednisolone Administration For this group, 40 randomly enrolled patients aged 18-65 years with relapsing-remitting multiple sclerosis that assist to the hospital and confirmed with a relapse, will be treated with intranasal methylprednisolone administration (1000 mg once a day for 3 days for moderate relapses or 5 days for severe ones) using a Mucosal Atomization Device (MAD Nasal). A written informed consent will be obtained from each participant or a legal representative whenever the participant could not provide consent	Drug: Nasal Methylprednisolone (MT); Group 2 will receive the dose intranasal equivalent to 1g of methylprednisolone for 3 or 5 days according to the severity of the relapse; Other Names: Nasal MT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients' score on the Expanded Disability Status Scale (EDSS) before and after treatment to assess clinical efficacy of treatments	The Expanded Disability Status Scale has a minimum score of 0, when the patient has no MS-related disability or abnormalities, and a maximum score of 10, when death is caused by MS.; Patients will be assessed with the EDSS prior to treatment and 30 days after the treatment ends	Days 0 and 30 after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of inflammatory cytokines and chemokines in peripheral blood before, during, and after treatment	Enzyme-Linked Immunosorbent Assay (ELISA) to detect inflammatory molecules will be performed in plasma derived from blood samples taken from patients prior to treatment, on day 5 of treatment and 30 days after treatment	Days 0, 5 and 30 after treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of lymphocyte subsets in peripheral blood before, during, and after treatment	•Flow cytometry will be performed using blood samples taken from patients prior to treatment, on day 5 of treatment and 30 days after treatment	Days 0, 5 and 30 after treatment
Shannon and Chao1 indexes in feces samples to determine diversity and composition of intestinal microbiota in patients before and after treatment	16S rRNA will be sequenced from isolated microbial DNA obtained from patient samples to determine global microbial composition prior to treatment and 30 days after treatment	Days 0 and 30 after treatment
Number of patients with adverse effects related to the methylprednisolone intranasal treatment as assessed by a questionnaire	• The physician will assess possible adverse effects of the treatment using a questionnaire 30 days after treatment	Day 30 after treatment

Collaborators and Investigators

• Sponsor: Universidad Nacional Autonoma de Mexico
• Collaborators: Instituto Nacional de Neurología y Neurocirugía

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2023
• Primary Completion (Estimated): February 25, 2026
• Study Completion (Estimated): July 5, 2026

Study Registration Dates

• First Submitted: April 25, 2023
• First Submitted That Met QC Criteria: January 15, 2024
• First Posted (Actual): January 25, 2024

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: March 31, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: intranasal administration; methylprednisolone; Multiple Sclerosis Relapsing Remitting
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis; Antineoplastic Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Neuroprotective Agents; Methylprednisolone Acetate; Prednisolone; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: BD2012-34CEC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Information exchange for research purposes
• IPD Sharing Time Frame: Upon study completion, by request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No