Metabolic Effects of an Ophiocordyceps Sinensis- and CoQ10-Based Formulation in Mild-to-Moderate Hypercholesterolemia (CORDICOL)

Participants will receive CORDICOL, a nutraceutical formulation containing Ophiocordyceps sinensis (200 mg) and Coenzyme Q10 (50 mg), administered as one capsule per day. The product will be provided free of charge by the Sponsor, noiVita S.r.l.s., exclusively for use in the study, ensuring standardized dosing and continuity of treatment throughout the study period.

CORDICOL is a nutraceutical formulation containing 200 mg of Ophiocordyceps sinensis extract and 50 mg of Coenzyme Q10 per capsule. Participants will take one capsule orally once daily for the duration of the treatment period. The intervention is intended to evaluate the effects of the formulation on lipid and glucose metabolism in subjects with mild-to-moderate hypercholesterolemia.

• Ophiocordyceps sinensis + Coenzyme Q10

Participants assigned to the placebo group will receive capsules identical in appearance, size, color, taste, and packaging to the active product, but containing no active ingredients. The placebo will be manufactured by a GMP-certified company and packaged in anonymized blisters identified only by the unique patient code assigned by the centralized system, ensuring treatment blinding throughout the study.

The placebo consists of capsules identical to the active CORDICOL capsules in appearance, size, color, taste, and packaging, but containing no active ingredients. Participants will take one capsule orally once daily for the duration of the treatment period. The placebo will be manufactured under GMP-compliant conditions and packaged in anonymized blisters identified by the unique participant code.

The primary endpoint of the study is represented by the percentage change in levels of LDL cholesterol (LDL-C) from baseline (T0) to end of treatment (week 12). LDL cholesterol is the main modifiable lipid factor associated with risk cardiovascular and is universally recognized as a priority therapeutic target in primary cardiovascular prevention. The evaluation of its variation represents therefore the most appropriate parameter to determine the metabolic efficacy of the study formulation

In addition to LDL cholesterol, the study will assess changes in total cholesterol, triglycerides, and HDL cholesterol, which plays an important role in reverse cholesterol transport and vascular protection.

Fasting blood glucose and fasting insulin concentrations will be assessed and used to calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. HOMA-IR is a continuous numerical index with a theoretical minimum value of 0 and no predefined maximum value. Higher HOMA-IR values indicate greater insulin resistance and therefore a worse outcome, whereas lower values indicate greater insulin sensitivity and therefore a better outcome. Changes in HOMA-IR from baseline will be evaluated to explore the possible impact of treatment on insulin sensitivity and carbohydrate homeostasis, which are closely related to alterations in lipid metabolism.

The impact of treatment on quality of life will be assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire. The EQ-5D-5L assesses health status across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, with five response levels for each dimension. Each dimension is scored from 1 (no problems) to 5 (extreme problems), with higher dimension scores indicating worse health status. The responses will be converted into a single EQ-5D-5L Index Value using the applicable country-specific value set. The Index Value ranges from values below 0 to 1, with 1 representing the best possible health state (perfect health); therefore, higher Index Values indicate better health-related quality of life, with values closer to 1 representing better health status. The joint use of this tool will allow biochemical outcomes to be integrated with the patient's subjective perception of health status and clinical benefit.

The benefit perceived by the participant will be assessed using a 7-point Likert-type Global Perceived Effect (GPE) scale designed to capture the participant's subjective perception of change following treatment. Each participant will report how their condition has changed compared with the pre-treatment phase by selecting one of seven possible responses: 1 = definitely worsened, 2 = worsened, 3 = did not improve, 4 = no change, 5 = partly improved, 6 = improved, and 7 = definitely improved. Higher scores indicate a greater perceived benefit and improvement in the participant's health status, whereas lower scores indicate a worse perceived outcome. The joint use of this tool will allow biochemical outcomes to be integrated with the participant's subjective perception of health status and clinical benefit.

The safety and tolerability of the study treatment will be evaluated throughout the study by systematically monitoring, recording, and assessing all adverse events (AEs; such as nausea, instetinal disorders, headache...) reported by participants or identified by the investigator. The occurrence, severity, duration, and potential relationship to the study treatment will be documented and evaluated in accordance with applicable clinical study procedures and regulatory requirements.