Metformin Treatment for Children With Obesity-associated Asthma

The Role of Metformin in Asthma Control in Obese/Overweight Children, a Randomized Placebo Controlled Clinical Trial

The goal of this clinical trial is to learn if metformin can improve asthma control in overweight and obese children with mild, moderate, or severe asthma. It will also evaluate the safety and metabolic effects of metformin in this population. The main questions the study aims to answer are:

1) Does metformin improve asthma control, as measured by the Asthma Control Test (ACT) score? 2) Does metformin improve lung function, reduce asthma exacerbations, and improve metabolic and inflammatory markers in overweight/obese children with asthma? Researchers will compare metformin with a placebo (a look-alike substance that contains no active drug) to see if metformin improves asthma outcomes in overweight/obese children with asthma. Participants will take either metformin or a placebo in addition to their standard asthma treatment during the study period. They will attend scheduled clinic visits for asthma assessments, lung function testing, and safety monitoring. Blood, stool, and saliva samples, along with clinical information, will be collected from participants to assess asthma control, and markers related to metabolism and inflammation. Participants will also complete asthma control questionnaires and report medication use and asthma symptoms throughout the study period.

The study is a randomized, double-blinded, placebo-controlled, parallel- group intervention trial aimed to recruit 182 overweight/obese children aged 10-17 years with mild, moderate, or severe persistent asthma from the outpatient Pediatric Pulmonology Department at Sidra Medicine, Qatar. Participants will be randomly assigned in a 1:1 ratio to receive either metformin or placebo for the intervention period of 26 weeks. The primary outcome is defined as an increase in the Asthma Control Test (ACT) score at the end of the treatment compared with baseline. Secondary outcomes include a decrease in annual rate of asthma exacerbations and corticosteroid use, as well as change in lung function, and pediatric asthma quality of life questionnaire (PAQLQ) score from baseline. Exploratory outcomes include changes in the body mass index, clinical parameters, plasma cytokine profile, plasma metabolomic and lipidomic profile, blood transcriptomic profile, and microbiome of gut and saliva after metformin/placebo intervention. Statistical analyses of all primary and secondary end points will be performed using intention-to-treat (ITT) principle and per protocol (PP) approaches.

Inclusion Criteria:

• Participant who are capable of giving assent and parentral consent
• Male/Female participant aged between10-17 years old,
• overweight/obese children (Overweight and obesity are defined as BMI equal and above the 85th percentile, and BMI above the 95th percentile for age and sex, respectively).
• Diagnosed with mild persistent, moderate persistent /severe asthma based on GINA guidelines within the 6 months prior to the recruitment date and having ACT score < 20, residing in Qatar
• Partcipants on standard asthma therapy for at least the last 6 months prior to the recruitment
• Participant who are currently not taking part in any other interventional study

Exclusion Criteria:

• Non-asthma chronic lung disease
• Broncho-pulmonary dysplasia
• Inflammatory bowel disease
• Syndromic disorders (e.g. Down's syndrome, Turner's syndrome)
• Inborn errors of metabolism
• Symptomatic or previously symptomatic congenital heart disease
• Craniofacial abnormalities
• Primary thoracic cage abnormalities
• Neuromuscular disorders
• Swallowing disorders
• Secondary endocrinopathies causing obesity
• Renal complications
• Ongoing treatment for cancer
• Taking metformin or GLP1 medication less than 3 months of the recruitment date
• Children diagnosed with type-1 diabetes