Evaluation of the Effects of Two Dietary Supplement Formulations on the Lipid Profile in Mild Hypercholesterolemia

A Single-blind, Parallel-group, Randomized, Placebo-controlled Clinical Trial, to Evaluate the Effects of Two Different Formulations of a Dietary Supplement on the Lipid Profile in Subjects with Mild Hypercholesterolemia

A single-center, randomized, parallel-group, double-blind, placebo-controlled clinical study followed by an open-label phase to evaluate the effects of a new formulation of a supplement on lipid profile in subjects with mild hypercholesterolemia who are non-responsive to the Mediterranean diet.

The study population consists of 99 subjects with mild hypercholesterolemia who are non-responsive to the Mediterranean diet. The participants will be divided into three groups:

Group A: Test Product A (study product) Group B: Test Product B (comparative product) Placebo group: placebo

The following visits are scheduled during the study:

T-2 (day -35) - Screening visit, 5 weeks before T0 T-1 (day -28) - Enrollment visit, 4 weeks before T0 T0 (day 0) - Randomization visit, baseline T1 (day 56) - Interim visit, 8 weeks after T0 T2 (day 112) - Final visit, 16 weeks after T0 After the first 8 weeks of the study (double-blind), all three groups will continue with only Product A for an additional 8 weeks. This experimental design aims to highlight whether any differences between Test Product A and Test Product B observed during the first 8 weeks can be minimized when both arms receive the same treatment. Additionally, the effect of Product A will be observed at 8 and 16 weeks, thus providing efficacy data over a longer treatment period. This may also provide insights into the potential achievement of a plateau. Regarding the placebo group, it will be possible to distinguish the effect of the diet alone from the combined effect of the diet and supplementation with Test Product A.

Study Overview

• Status: Recruiting
• Conditions: Supplementation; Hypercholesterolemia and Hyperlipidemia
• Intervention / Treatment: Dietary supplement: Test Product A; Dietary supplement: Test Product B; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 99
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Arrigo Francesco Giuseppe Cicero, Prof.; Phone Number: +39 512142224; Email: arrigo.cicero@unibo.it

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • S. Orsola-Malpighi University Hospital
    • Contact: Arrigo F.G. Cicero, Prof.; Phone Number: +39 512142224; Email: arrigo.cicero@unibo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Prevention of cardiovascular disease
• Low cardiovascular risk (< 5%)
• Sub-optimal serum levels of LDL-C (130-136 mg/dl; 3.37-4.14 mmol/l) and/or non-HDL-C (160-190 mg/dl; 4.14-4.92 mmol/l) at T-2
• Signature of informed consent.

Exclusion Criteria:

• Patients with cardiovascular disease (in secondary prevention) or at risk of cardiovascular disease after 10 years (cardiovascular risk >/= 5)
• diabetes mellitus
• Taking hypolipemiants, supplements or drugs that may involve lipid metabolism
• Hypertension treatment not stabilized for at least 3 months
• History of ongoing kidney, thyroid, gastrointestinal, muscle or liver disease
• Any medical-surgical treatment that may limit adherence to the study protocol
• Pregnant and/or breastfeeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: Placebo; Placebo does not contain functional components and is indistinguishable from Product Test B. After the fist 8 weeks, this arm will continue with the intake of the Product Test A for other 8 weeks.
Experimental: Test Product A; Innovative formulation of dietary supplement	Dietary supplement: Test Product A; Innovative formulation of a dietary supplement for mild hypercholesterolemia. Test Product A will be admistered daily for 8 weeks. After the fist 8 weeks, this arm will continue with the intake of the Product Test A for other 8 weeks.
Active Comparator: Test Product B; Classic formulation of dietary supplement	Dietary supplement: Test Product B; Classic formulation of a dietary supplement for mild hypercholesterolemia. After the fist 8 weeks, this arm will continue with the intake of the Product Test A for other 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low-Density Lipoprotein Cholesterol (LDL-C) Serum Concentration After Target Product A Treatment	Evaluation of absolute value change in Low-Density Lipoprotein Cholesterol (LDL-C) serum concentration (expressed as mg/dL), at 8 weeks (T1) of dietary supplementation with Test Product A vs baseline (T0).	At baseline (T0) and at 8 weeks.
Low-Density Lipoprotein Cholesterol (LDL-C) Serum Concentration After Target Product A Treatment	Evaluation of the percentage variation (%) in Low-Density Lipoprotein Cholesterol (LDL-C) serum concentration at 8 weeks (T1) of dietary supplementation with Test Product A, compared to baseline (T0).	At baseline (T0) and at 8 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low-Density Lipoprotein Cholesterol (LDL-C) Serum Concentration After Treatment with Target Product B	Evaluation of absolute value change in Low-Density Lipoprotein Cholesterol (LDL-C) serum concentration (expressed as mg/dL), at 8 weeks (T1) of dietary supplementation with Test Product B vs baseline (T0).	At baseline (T0) and at 8 weeks.
Low-Density Lipoprotein Cholesterol (LDL-C) Serum Concentration After Treatment with Target Product B	Evaluation of the percentage change (%) in Low-Density Lipoprotein Cholesterol (LDL-C) serum concentration at 8 weeks (T1) of dietary supplementation with Test Product B, compared to baseline (T0)	At baseline (T0), and at 8 weeks (T1)
Serum Total Cholesterol Concentration (TC)	Evaluation of the absolute value change in Serum Total Cholesterol concentration (TC; expressed as mg/dL) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Serum Total Cholesterol Concentration (TC)	Evaluation of the percentage change (%) in Serum Total Cholesterol concentration (TC) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Low-Density Lipoprotein Cholesterol (LDL-C) Serum Concentration	Evaluation of the absolute value change in serum concentrations of Low-Density Lipoprotein Cholesterol (LDL-C; expressed as mg/dL) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Low-Density Lipoprotein Cholesterol (LDL-C)	Evaluation of the percentage change (%) in Low-Density Lipoprotein Cholesterol (LDL-C) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
High-Density Lipoprotein Cholesterol (HDL-C)	Evaluation of the absolute value change in serum concentrations of High-Density Lipoprotein Cholesterol (HDL-C; expressed as mg/dL) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
High-Density Lipoprotein Cholesterol (HDL-C)	Evaluation of the percentage change (%) in serum concentrations of High-Density Lipoprotein Cholesterol (HDL-C) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Non High-Density Lipoprotein Cholesterol (Non-HDL-C)	Evaluation of the absolute value change in serum concentrations of Non High-Density Lipoprotein Cholesterol (Non-HDL-C; expressed in mg/dL) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Non High-Density Lipoprotein Cholesterol (Non-HDL-C)	Evaluation of the percentage change (%) in serum concentrations of Non High-Density Lipoprotein Cholesterol (Non-HDL-C) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Triglycerides (TG)	Evaluation of absolute value change in Triglycerides (TG) serum concentration (expressed as mg/dL), at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Triglycerides (TG)	Evaluation of the percentage change (%) in serum concentrations of Triglycerides (TG) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Apolipoprotein B	Evaluation of the absolute value change in serum concentrations of Apolipoprotein B (expressed as mg/dL) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0)	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Apolipoprotein B	Evaluation of the percentage change (%) in serum concentrations of Apolipoprotein B at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Systolic Blood Pressure	Evaluation of the absolute value change in Systolic Blood Pressure (expressed as mmHg) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Systolic Blood Pressure	Evaluation of the percentage change (%) in Systolic Blood Pressure at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Diastolic Blood Pressure	Evaluation of the absolute value change in Diastolic Blood Pressure (expressed as mmHg) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Diastolic Blood Pressure	Evaluation of the percentage change (%) in Diastolic Blood Pressure at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Mean Arterial Pressure	Evaluation of the absolute change in Mean Arterial Pressure (expressed in mmHg) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Mean Arterial Pressure	Evaluation of the percentage change (%) in Mean Arterial Pressure at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Pulse Pressure	Evaluation of the absolute change in Pulse Pressure (expressed in mmHg) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Pulse Pressure	Evaluation of the percentage change (%) in Pulse Pressure at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Flow-Mediated Dilation (FMD) - Endothelial Function	Evaluation of the percentage change (%) in Flow-Mediated Dilation (FMD), measured as the percentage increase in artery diameter during hyperemia, at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0)	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Body Weight	Evaluation of the absolute value change in Weight (kg) at 8 weeks (T1) and 16 weeks (T2), compared to baseline (T0), within and between groups.	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Body Weight	Evaluation of the percentage change (%) Weight at 8 weeks (T1) and 16 weeks (T2), compared to baseline (T0), within and between groups.	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Body Mass Index (BMI)	Evaluation of the absolute value change in Body Mass Index (BMI; kg/m²), at 8 weeks (T1) and 16 weeks (T2), compared to baseline (T0), within and between groups.	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Body Mass Index (BMI)	Evaluation of the percentage change (%) in Body Mass Index (BMI), at 8 weeks (T1) and 16 weeks (T2), compared to baseline (T0), within and between groups.	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Glutamic Oxaloacetic Transaminase (GOT)	Evaluation of the absolute value change in Glutamic Oxaloacetic Transaminase (GOT) concentration (expressed as U/L) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Glutamic Oxaloacetic Transaminase (GOT)	Evaluation of the percentage change (%) in Glutamic Oxaloacetic Transaminase concentration (GOT; expressed as U/L) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Gamma-Glutamyl Transferase (Gamma - GT)	Evaluation of the absolute value change in Gamma-Glutamyl Transferase (Gamma - GT) concentration (expressed as U/L) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Gamma-Glutamyl Transferase (Gamma - GT)	Evaluation of the percentage change (%) in Gamma-Glutamyl Transferase (Gamma - GT) concentration at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Glutamic Pyruvate Transaminase (GPT)	Evaluation of the absolute value change in Glutamic Pyruvate Transaminase (GPT) concentration (expressed as U/L) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Glutamic Pyruvate Transaminase (GPT)	Evaluation of the percentage change (%) in Glutamic Pyruvate Transaminase (GPT) concentration at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Serum Uric Acid	Evaluation of the absolute value change in Serum Uric Acid concentration (expressed as mg/dL) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Serum Uric Acid	Evaluation of the percentage change (%) in Serum Uric Acid concentrations at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At Baseline (T0), at 8 weeks (T1), and at 16 weeks (T2)
Creatinine Concentration	Evaluation of the absolute value change in Creatinine Concentration (expressed as mg/dL) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At Baseline (T0), at 8 weeks (T1), and at 16 weeks (T2).
Creatinine Concentration	Evaluation of the percentage change (%) in Creatinine Concentration at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1) and 16 weeks (T2).
Creatine phosphokinase (CPK) Concentration	Evaluation of the absolute value change in Creatine Phosphokinase (CPK) concentration (expressed in mcg/L) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline.	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Creatine phosphokinase (CPK) Concentration	Evaluation of the percentage change (%) in Creatine Phosphokinase (CPK) concentration at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline.	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Number of subjects with LDL-C normal concentration	Evaluation at 8 weeks (T1) and 16 weeks (T2) of the number of subjects in each group with LDL-C levels (mg/dL) within the normal range of concentration.	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Fasting Blood Glucose Concentration	Evaluation of the absolute value change in Fasting Blood Glucose concentration (expressed as mg/dL) at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Fasting Blood Glucose Concentration	Evaluation of the percentage change (%) in Fasting Blood Glucose concentration at 8 weeks (T1) and 16 weeks (T2), within and between groups, compared to baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Cardiovascular Risk (CV)	Assessment of the Cardiovascular Risk (CV), based on Cardiovascular Risk Chart, at 8 weeks (T1) and 16 weeks (T2), compared with baseline (T0).	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Patients' compliance with the treatment	Assessment of patient's compliance with the treatment by calculating the percentage ratio between the number of capsules taken and the number of capsules expected at 8 weeks (T1), and 16 weeks (T2), in each group and intergroup vs baseline (T0). Number of patients: 99; assigned treatment: Test Product A; Test product B; Placebo.	At baseline (T0), 8 weeks (T1), and 16 weeks (T2)
Patients' Tolerability of the assigned treatment	Evaluation of Patients' Tolerability of the assigned treatment using the Visual Analogue Scale (VAS), with scores ranging from 1 to 10, where higher scores indicate greater tolerability, assessed at 8 weeks (T1) and 16 weeks (T2), with intra-group and inter-group evaluations. Number of patients: 99; assigned treatments: Test Product A, Test Product B, Placebo.	At 8 weeks (T1) and at 16 weeks (T2)
Patient acceptability of the assigned treatment	Evaluation of patient acceptability of the assigned treatment using the Visual Analogue Scale (VAS), with scores ranging from 1 to 10, where higher scores indicate greater acceptability, assessed at 8 weeks (T1) and 16 weeks (T2), with intra-group and inter-group evaluations. Number of patients: 99; assigned treatments: Test Product A, Test Product B, Placebo.	At 8 weeks (T1) and at 16 weeks (T2)
Patients' adherence to diet	Assessment of patients' adherence to diet based on the food history questionnaire recording at baseline (T0), 8 weeks (T1), 16 weeks (T2), and intra-group and intergroup evaluation.	Baseline (T0), 8 weeks (T1), 16 weeks (T2)
Implementation of patients' lifestyle	Measurement of the rate of successful implementation of patients' lifestyle changes, through the evaluation of the prescription of physical exercise (brisk walking or cycling for 20-30 minutes, 3-5 times per week) by the investigator, assessed at baseline (T0), 8 weeks (T1), and 16 weeks (T2), with both intra-group and inter-group evaluations	At Baseline (T0), at 8 weeks (T1), and at 16 weeks (T2)
Monitoring of adverse events	Collection of adverse events after treatment with product A, B and placebo	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: IBSA Farmaceutici Italia Srl
• Collaborators: Informapro Srl

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: January 8, 2025
• First Submitted That Met QC Criteria: January 30, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 30, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: dietary supplement; supplement; lipid profile; mild hypercholesterolemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Dyslipidemias; Lipid Metabolism Disorders; Hypercholesterolemia; Hyperlipidemias
• Other Study ID Numbers: COLE_TRIAL_2023 (Other Identifier: IBSA Farmaceutici Italia Srl)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Results, data, workflows, and tools may be made available through publication, presentations at scientific meetings.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No