Efficacy of Colecalciferol Supplementation in Patients with Chronic Periodontitis and Vitamin D Deficiency: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this clinical trial is to evaluate the **efficacy** of vitamin D3 as an adjunct therapy to non-surgical periodontal treatment in reducing the number of residual probing pocket depths ≥ 5mm in participants with chronic **periodontitis**. This is clinically relevant as it aims to enhance the effectiveness of standard periodontal treatments, potentially leading to improved patient outcomes in managing chronic periodontitis.

Secondary objectives include:

• Monitoring changes in secondary periodontal indices such as probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BoP), plaque control (O’Leary), and PPD ≥ 6, 5, or 4 mm.
• Assessing changes in 25(OH)D3 serum concentration.
• Evaluating the overall safety of the products, D-CURE® and placebo.

The clinical trial involves a study population of **Caucasian** males and females over the age of 18, with a confirmed diagnosis of stage III or IV **periodontitis**. Participants must have more than 15 natural teeth and a 25(OH)D3 level of less than 30 ng/mL at the screening visit. The trial does not include a vulnerable population. The sponsor has not provided the total number of participants. Participants are required to comply with all trial procedures and provide written informed consent. Women of childbearing potential must use highly effective contraception during the trial and for at least 28 days following the last dose of the investigational product. The trial aims to evaluate the efficacy of vitamin D3 as an adjunct therapy to non-surgical periodontal treatment.

The clinical trial is designed to evaluate the efficacy of **vitamin D3** supplementation as an adjunct therapy to non-surgical periodontal treatment in participants with chronic **periodontitis**. This study is a randomized, double-blind, placebo-controlled trial with a parallel design. The trial is expected to last until June 30, 2026, with recruitment starting on September 1, 2023. Participants will be randomly assigned to receive either the active treatment, D-CURE 25000 UI capsules containing **colecalciferol**, or a placebo of vitamin D, both administered orally. The maximum treatment period is 24 weeks.

Study visits are structured to ensure comprehensive data collection and participant safety. The inclusion visit, or screening, will confirm eligibility based on criteria such as age, diagnosis of stage III or IV periodontitis, and vitamin D deficiency. Participants must have more than 15 natural teeth and a 25(OH)D3 level below 30 ng/mL. Following the screening, baseline measurements will be taken at visit 2 (V2). Subsequent follow-up visits are scheduled at week 12 (V3) and week 24 (V4), with the primary endpoint being the absolute change in the number of residual probing pocket depths (PPD) ≥ 5mm from baseline to week 24. Secondary endpoints include changes in mean PPD, clinical attachment level, and serum 25(OH)D3 concentration, among others.

The expected length of participant involvement is approximately 24 weeks, with conditions for early termination including non-compliance with trial procedures or withdrawal of consent. Safety assessments will be conducted throughout the trial, monitoring for adverse events, serious adverse events, and suspected unexpected serious adverse reactions. The trial aims to provide valuable insights into the potential benefits of vitamin D3 supplementation in managing periodontitis, with the ultimate goal of improving periodontal health outcomes in affected individuals.

The clinical trial involves the administration of **D-CURE 25000 UI gélules**, which contains the active substance **colecalciferol**, also known as **vitamin D3**. This experimental medication is provided in the form of hard capsules, with each capsule containing 25,000 international units (IU) of colecalciferol. The route of administration is oral, and the maximum total dose allowed during the trial is 600,000 IU over a treatment period of up to 24 weeks. The medication is manufactured by Laboratoires SMB S.A. and is identified by the marketing authorization number BE535191. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.

In addition to the experimental treatment, a **placebo of vitamin D** is used as a comparator in this double-blind, placebo-controlled trial. The placebo is designed to mimic the appearance and administration route of the active treatment, ensuring that neither the participants nor the investigators are aware of the treatment allocation. The placebo is administered orally, in a manner consistent with the experimental medication, to maintain the integrity of the study design and to accurately assess the efficacy of the active treatment.

The efficacy of vitamin D3 supplementation as an adjunct therapy in participants with chronic periodontitis will be assessed through a series of primary and secondary endpoints. The primary endpoint is the absolute change from baseline to week 24 in the number of residual probing pocket depths (PPD) of ≥ 5mm. Secondary endpoints include the absolute change from baseline to weeks 12 and 24 in mean PPD, mean clinical attachment level (CAL), and the number of residual PPDs of ≥ 4mm, ≥ 5mm, and ≥ 6mm. Additional secondary endpoints involve changes in bleeding on probing (BoP), plaque control (O’Leary), and 25(OH)D3 serum concentration, as well as the percentage of participants with ≤ 4 sites with PPD ≥ 5mm at week 24 and those reaching 25(OH)D3 serum concentrations above 30 ng/ml at week 24.

Measurements will be collected at baseline (V2), week 12 (V3), and week 24 (V4) using validated clinical assessments and laboratory tests. The incidence of adverse events, including serious adverse events and suspected unexpected serious adverse reactions, will also be monitored. Changes in laboratory data, specifically serum concentrations of calcium and phosphate, will be evaluated throughout the trial. These assessments will provide comprehensive data on the efficacy of vitamin D3 in improving periodontal health in the study population.