Evaluation of Sodium Cromoglicate Efficacy and Safety in Symptomatic Management of Fatigue in Multiple Sclerosis: A Randomized, Placebo-Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of oral disodium cromoglycate (200-400 mg) compared to placebo in alleviating fatigue in patients with **multiple sclerosis**. Fatigue is a common and debilitating symptom in multiple sclerosis, significantly impacting patients' quality of life and daily functioning. Addressing this symptom can lead to improved patient outcomes and overall well-being.

Secondary objectives include:

• Evaluating the efficacy of the treatment on urinary dysfunction in patients with urinary incontinence.
• Assessing the effect of the treatment on various aspects such as quality of life, emotional state, bowel function, sexual function, labor productivity, disease progression, and functional magnetic resonance imaging.
• Evaluating the safety profile of oral disodium cromoglycate in this patient population.

The clinical trial focuses on evaluating the efficacy of oral disodium cromoglycate in patients with **multiple sclerosis**. The study population includes both male and female participants aged between 18 and 65 years. Participants are required to have a diagnosis of multiple sclerosis according to the 2017 McDonald criteria, with a follow-up period of more than 6 months and clinical stability, defined as no flare-ups or new lesions, in the last 6 months. The trial includes individuals with an Expanded Disability Status Scale (EDSS) score ranging from 1.0 to 6.5 points. Participants must also exhibit moderate fatigue for at least 6 months, as indicated by a score of 33 or more on the Modified Fatigue Impact Scale (MFIS), and urinary dysfunction, defined by a score of 2 points or more on the ABSST Test. The sponsor has not provided information regarding the total number of participants. The trial does not involve a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria.

The clinical trial is designed to evaluate the **efficacy** and safety of **sodium cromoglicate** as a symptomatic treatment for patients with **multiple sclerosis**. This is a Phase IV, randomized, double-blind, placebo-controlled trial. The study will involve the administration of oral disodium cromoglycate at doses ranging from 200 to 400 mg, compared to a placebo. The primary objective is to assess the impact on fatigue using the Modified Fatigue Impact Scale (MFIS) at the end-of-treatment visit, with secondary endpoints including various quality of life and symptom scales.

The trial is expected to commence recruitment on September 25, 2024, and conclude by April 30, 2026. Participants will be involved for a maximum treatment period of 9 months. The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age, diagnosis, and symptom severity; multiple follow-up visits to monitor progress and collect data on primary and secondary endpoints; and a final end-of-study visit to evaluate overall outcomes and any adverse events.

Inclusion criteria require participants to be aged between 18 and 65 years, have a diagnosis of multiple sclerosis according to the 2017 McDonald criteria, and exhibit moderate fatigue and urinary dysfunction. Participants will be excluded if they do not meet these criteria or if they experience significant clinical instability. Conditions for early termination from the study include the occurrence of severe adverse events or withdrawal of consent by the participant. The trial will ensure rigorous monitoring to maintain participant safety and data integrity throughout the study duration.

The clinical trial involves the administration of **sodium cromoglicate**, a chemical compound known for its role in managing symptoms associated with various conditions. In this study, sodium cromoglicate is utilized as an experimental medication to evaluate its efficacy in treating fatigue in patients with multiple sclerosis. The pharmaceutical form of sodium cromoglicate is identified as PHF00006MIG, and it is administered orally. The dosage ranges from 200 mg to 400 mg per administration, with a maximum daily dose of 1200 mg. The treatment period extends up to 9 weeks, with the frequency of administration tailored to the individual needs of the participants, ensuring compliance with the study protocol. Monitoring of participant compliance is conducted through regular assessments and documentation of dosing schedules.

The study also includes a **placebo** as a comparator treatment to evaluate the efficacy of sodium cromoglicate. The placebo is designed to mimic the experimental medication in appearance but contains no active pharmaceutical ingredients. It serves as a control to help determine the true effect of the sodium cromoglicate treatment. The placebo is administered in a manner consistent with the experimental medication, ensuring that participants and investigators remain blinded to the treatment assignments. This approach allows for an unbiased assessment of the treatment's efficacy and safety in the study population.

The efficacy of the treatment in this clinical trial will be assessed using several primary and secondary endpoints. The primary endpoints include the Modified Fatigue Impact Scale (MFIS) at the end-of-treatment visit compared to baseline, the Fatigue Severity Scale (FSS), and the Patient-Reported Outcome Measurement Information System for Fatigue in Multiple Sclerosis (PROMIS-SF-Fatigue). These scales are designed to evaluate the impact of fatigue, a common symptom in patients with multiple sclerosis, and will be measured at specified timepoints throughout the trial.

Secondary endpoints will encompass a range of assessments to provide a comprehensive evaluation of the treatment's efficacy. These include the Actionable Bladder Symptom Screening Tool (ABSST), Urinary Incontinence Questionnaire (ICIQ-SF), Sandvik Incontinence Severity Test, Bladder Control Scale (BLCS), and the International Prostate Symptom Scale (IPSS). Additionally, quality of life will be assessed using the SF-36 and EQ-5D questionnaires, while psychological impacts will be measured with the Hospital Anxiety and Depression Scale (HADS) and the Beck Depression Inventory (BDI). The Expanded Disability Status Scale (EDSS) will be used to evaluate disability status, and various tests such as the 25 steps test and the 9 sticks test will assess physical function.

Further assessments will include imaging studies to evaluate new lesions and atrophy, as well as laboratory tests to analyze cytokine levels and lymphocyte activation. Optical coherence tomography will be used to assess axonal damage and macular volume. The trial will also monitor treatment-related adverse events and collect analytical values from blood and urine tests. These comprehensive assessments will be conducted at various timepoints, including baseline and each treatment visit, to ensure a thorough evaluation of the treatment's efficacy in managing symptoms of multiple sclerosis.