Effect of probiotic and zinc supplementation separately and in combination on reducing the complication of influenza-like syndrome during therapy by beta-interferon in patients with relapsing-remitting multiple sclerosis: a randomized clinical trial

To assess the effect of effect of probiotic and zinc supplementation separately and in combination on reducing the complication of influenza-like syndrome during therapy by beta-interferon in patients with relapsing-remitting multiple sclerosis

This is a randomized clinical trial, phase II, in which 60 eligible patients will be randomly assigned to the intervention and control groups

The eligible patients with relapsing-remitting multiple sclerosis referring to the Imam Khomeini Hospital in Hamadan city during the study period will be enrolled in the trial.

Inclusion criteria: age 20 to 40 years old; relapsing-remitting multiple sclerosis; corticosteroid therapy for at least 3 weeks. Exclusion criteria: pregnancy or breastfeeding; receiving influenza vaccine; respiratory infection in the past 2 weeks; using alcohol or opioid drugs in the past 2 months; autoimmune diseases or immunodeficiency syndrome; abdominal surgery; short bowel syndrome; mesenteric Ischemia; history of tuberculosis or AIDS.

Intervention group 1: Beta-interferon-1a 30 micrograms once a week intramuscular and Beta-interferon-1b 250 micrograms every-other-day subcutaneously for 3 months plus tablet zinc oxide 10 mg daily for 3 months and capsule probiotic 500 mg daily for 3 months. Intervention group 2: Beta-interferon-1a 30 micrograms once a week intramuscular and Beta-interferon-1b 250 micrograms every-other-day subcutaneously for 3 months plus tablet zinc oxide 10 mg daily for 3 months. Intervention group 3: Beta-interferon-1a 30 micrograms once a week intramuscular and Beta-interferon-1b 250 micrograms every-other-day subcutaneously for 3 months plus capsule probiotic 500 mg daily for 3 months.

Primary outcome: influenza-like syndrome; secondary outcome: gastrointestinal complications

The patients will be randomly assigned to intervention groups using block randomization. For this purpose, we will prepare six sheets of paper, writing on two sheets the name of the intervention 1 and on two other sheets the name of the intervention 2 and on the third two sheets the name of the intervention 3. The paper sheets will be pooled, placed in a container, and randomly drawn one at a time for each patient without replacement until all six sheets are drawn. The six paper sheets will be then placed back into the container, and this action repeated until the sample size is reached.