Efficacy Comparison of Monthly Bolus Versus Daily Colecalciferol Supplementation in Correcting Vitamin D Deficiency in Obese Pediatric Patients

The primary objective of this study is to compare the **efficacy** of two vitamin D supplementation regimens, specifically monthly bolus substitution versus daily substitution, in increasing serum vitamin D levels in obese children and adolescents. This is clinically relevant as vitamin D deficiency is prevalent in this population and can lead to various health issues, including impaired bone health and metabolic disorders.

Secondary objectives include:

• To evaluate the **safety** and tolerance of both treatments.
• To evaluate the compliance of both treatments.
• To describe the influence of skin type, physical activity, general health, and sources of vitamin D on serum vitamin D levels at M3 by treatment arm.
• To compare bone mineral density (DXA) at baseline for the subgroup > 10 years old with a preexisting cohort of healthy children and adolescents.
• To describe the bone mineral density (DXA) in obese children and adolescents at M0.
• To evaluate the variation of the PTH serum level between M0 and M3.

The clinical trial involves **obese children and adolescents** with an age range of 5 to 17 years. The study population includes both male and female participants, and it is noted that the population is considered vulnerable. The sponsor has not provided the total number of participants. Participants were selected based on specific criteria, including a body mass index (BMI) greater than the 97th percentile for their age and gender, as defined by the World Health Organization (WHO) references. Additionally, participants must be affiliated with or benefit from the national health system. The trial aims to evaluate the efficacy of two vitamin D supplementation regimens in increasing serum vitamin D levels in this demographic.

The clinical trial is designed to evaluate the efficacy of two **vitamin D** supplementation regimens in increasing serum vitamin D levels in obese children and adolescents. This study is a randomized, controlled trial with an open-label design, comparing monthly bolus substitution with daily substitution. The trial is expected to last for a total duration of three months, with participant involvement spanning the same period. The primary endpoint is the measurement of vitamin D (25(OH)D) serum levels in each treatment arm after three months of treatment initiation. Secondary endpoints include assessments of calcium and phosphate levels in blood and urine, bone mineral density, and changes in parathyroid hormone (PTH) serum levels.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (5 to 18 years), obesity defined by BMI, and consent from parents or legal guardians. Follow-up visits will occur at the start of the trial (M0) and at the end of the trial (M3), where various assessments and sample collections will be conducted. The end-of-study visit will coincide with the final follow-up visit, marking the conclusion of the participant's involvement in the trial.

Participants are expected to adhere to the assigned supplementation regimen for the entire three-month period. Conditions that may lead to early termination from the study include non-compliance with the treatment protocol, withdrawal of consent, or any adverse events that compromise participant safety. The trial is categorized as low-intervention, as the investigational medicinal products are authorized and used in accordance with their marketing authorization, posing minimal additional risk to participants compared to standard clinical practice.

The clinical trial involves the administration of two different **colecalciferol** formulations to evaluate their efficacy in treating vitamin D deficiency in obese children and adolescents. The first experimental medication is **ZYMAD 50,000 UI**, an **oral solution** provided in ampoules. This formulation contains **colecalciferol** as the active substance, also known as **vitamin D3**. The medication is administered orally as a monthly bolus, with a maximum daily dose of 50,000 IU and a total maximum dose of 100,000 IU over a treatment period of three months. The pharmaceutical form is a solution buvable en ampoule, and the product is manufactured by ROTTAPHARM SAS in France.

The second experimental medication is **ZYMAD 10,000 UI/ml**, an **oral drops** formulation. This product also contains **colecalciferol** as the active ingredient. It is administered orally in daily doses, with a maximum daily dose of 1,200 IU and a total maximum dose of 100,800 IU over the same three-month treatment period. The pharmaceutical form is a solution buvable en gouttes, and it is also produced by ROTTAPHARM SAS in France. Both formulations are chemically derived and are not classified as pediatric formulations. The trial aims to compare the efficacy of these two regimens in increasing serum vitamin D levels in the target population.

Efficacy in this clinical trial will be assessed by comparing the effectiveness of two vitamin D supplementation regimens—monthly bolus substitution versus daily substitution—in increasing serum vitamin D levels in obese children and adolescents. The primary endpoint for evaluating efficacy is the **Vitamin D (25(OH)D) serum level** in each treatment arm, measured three months after the initiation of the treatment. Secondary endpoints include additional assessments at baseline (M0) and three months (M3), such as serum levels of vitamin D, calcium, and phosphorus, as well as urinary calcium, phosphorus, and calcium/creatinine ratios. The amount of treatment taken will be compared to the theoretical treatment quantity, with data collected through patient diaries and the weighing of returned treatments for the daily arm, and the description of taken ampoules for the bolus arm.

Other secondary endpoints involve evaluating the type of skin (phototype), physical activity, sun exposure, and dietary intakes using specific questionnaires at M0, and measuring bone mineral density (DXA) for patients aged 10 years and older at M0, with comparisons to data from a healthy control cohort. Additionally, changes in parathyroid hormone (PTH) serum levels between M0 and M3 will be analyzed. These efficacy parameters will be collected and analyzed at specified timepoints to determine the relative efficacy of the two supplementation regimens in correcting blood vitamin D levels.