Effect of Compound (Cardiol Forte) on Lipid And Glycemic Parameters in Low Cardiovascular Risk Individuals (CLARISKI)

A Randomized, Double-Blind, Placebo-Controlled, Two-Arm, Parallel-Group Clinical Trial With an Open-Label Extension to Evaluate the Effects of a Combination Dietary Supplement (Cardiol Forte) on Lipid and Glycemic Parameters in Subjects at Low Cardiovascular Risk With Suboptimal Cholesterol Levels

This study will evaluate the effects of a combination dietary supplement, Cardiol Forte, on lipid and glycemic parameters in adults at low cardiovascular risk with suboptimal cholesterol levels. After a 14- to 28-day run-in period with standardized dietary and behavioral instructions, 50 participants will be randomized in a 1:1 ratio to receive either Cardiol Forte or matching placebo for 8 weeks under double-blind conditions. After completion of the double-blind phase, all participants will receive Cardiol Forte for an additional 8 weeks in an open-label extension. The primary objective is to compare the change in non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to Week 8 between Cardiol Forte and placebo. Secondary objectives include evaluation of other lipid parameters, fasting plasma glucose, Omega-3 Index, selected inflammatory and liver-related markers, and endothelial reactivity.

Study Overview

• Status: Not yet recruiting
• Conditions: Dyslipidemia
• Intervention / Treatment: Dietary supplement: Cardiol Forte; Other: Placebo

Detailed Description

This monocentric, randomized, double-blind, placebo-controlled, parallel-group clinical trial is designed to evaluate the effects of a combination dietary supplement, Cardiol Forte, on lipid and glycemic parameters in adults at low cardiovascular risk with suboptimal cholesterol levels. In routine clinical practice, many individuals in primary cardiovascular prevention have mildly to moderately altered lipid levels that do not necessarily require immediate pharmacological treatment, but may still benefit from non-pharmacological strategies aimed at improving cardiometabolic risk factors. Cardiol Forte contains omega-3 fatty acids, artichoke leaf extract, bergamot extract, olive extract standardized in hydroxytyrosol, coenzyme Q10, folic acid, and vitamin E, and may have favorable effects on lipid metabolism and related cardiometabolic parameters.

A total of 50 participants will be enrolled. After screening and a 14- to 28-day run-in period with standardized dietary and behavioral instructions, eligible participants will be randomized in a 1:1 ratio to receive either Cardiol Forte or matching placebo for 8 weeks under double-blind conditions. After completion of the double-blind phase, all participants will enter an 8-week open-label extension and will receive Cardiol Forte. Study product will be administered orally at a dose of 2 capsules per day, preferably 15 to 30 minutes before dinner. The total duration of participation will therefore be 16 weeks, in addition to the run-in period.

The primary objective is to compare the change in plasma non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to the end of the 8-week double-blind phase between Cardiol Forte and placebo. Secondary objectives include evaluation of changes in total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, triglycerides, remnant cholesterol, fasting plasma glucose, Omega-3 Index, triglyceride-glucose index, liver-related indices, uric acid, high-sensitivity C-reactive protein, and endothelial reactivity. Participants will attend screening, randomization, end-of-double-blind, and final study visits. Blood samples for efficacy and safety assessments will be collected at scheduled visits, Omega-3 Index will be assessed at baseline, Week 8, and Week 16, and endothelial reactivity will be assessed by flow-mediated dilation. Safety will be monitored throughout the study through adverse event collection, vital signs, clinical assessments, and laboratory evaluations.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Arrigo Francesco Giuseppe Cicero, MD, PhD; Phone Number: +39051214290; Email: arrigo.cicero@unibo.it

Study Locations

• Italy
  • BO
    • Bologna, BO, Italy, 40100
      • Cardiovascular Internal Medicine Unit, IRCCS University Hospital of Bologna, Bologna, Italy
      • Contact: Arrigo Francesco Giuseppe Cicero, MD, PhD; Phone Number: +39051214290; Email: arrigo.cicero@unibo.it
      • Sub-Investigator: Valentina Di Micoli, BD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female aged 18 to 79 years
• Individuals in primary cardiovascular prevention
• Estimated 10-year cardiovascular risk <10%
• Screening non-HDL-C between 140 and 220 mg/dL, or screening LDL-C between 110 and 190 mg/dL
• Ability to communicate adequately, to be understood, and to comply with the study requirements
• Willingness to participate in the study and provision of written, signed, and dated informed consent

Exclusion Criteria:

• Triglycerides >400 mg/dL at screening
• Type 1 or type 2 diabetes mellitus
• Body mass index >35 kg/m²
• Current treatment with lipid-lowering drugs or use of dietary supplements active on lipid metabolism
• Antihypertensive treatment not stabilized for at least 3 months
• Known clinically significant alterations of thyroid, hepatic, and/or renal function
• Women of childbearing potential not using adequate contraceptive methods
• Pregnancy or breastfeeding
• Any medical or surgical condition that, in the investigator's judgment, could make adherence to the protocol difficult or inconsistent, compromise participant safety, or interfere with study completion
• Known intolerance or hypersensitivity to any component of the study products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Weeks 0-8: double-blind phase; placebo, 2 capsules orally once daily. Weeks 8-16: open-label phase; Cardiol Forte, 2 capsules orally once daily.	Dietary supplement: Cardiol Forte; Each capsule of Cardiol Forte contains fish oil 5025 TG 550.488 mg, corresponding to total omega-3 fatty acids 456 mg, of which eicosapentaenoic acid (EPA) 275 mg and docosahexaenoic acid (DHA) 137 mg; artichoke extract leaves (Altilix®) 150 mg; Citrus bergamia Risso et Poit. dry extract (BPF®) 100 mg; Cynara scolymus L. dry extract 10 mg; olive fruit dry extract standardized to 9% hydroxytyrosol 55.600 mg, corresponding to hydroxytyrosol 5.004 mg; coenzyme Q10 10 mg; folic acid 0.3 mg; and vitamin E 12 mg.; Other: Placebo; Matching placebo soft capsules are identical to Cardiol Forte in appearance, odour, and taste and contain no active ingredients.
Experimental: Dietary supplement - Cardiol Forte; Weeks 0-8: double-blind phase; Cardiol Forte, 2 capsules orally once daily. Weeks 8-16: open-label phase; Cardiol Forte, 2 capsules orally once daily.	Dietary supplement: Cardiol Forte; Each capsule of Cardiol Forte contains fish oil 5025 TG 550.488 mg, corresponding to total omega-3 fatty acids 456 mg, of which eicosapentaenoic acid (EPA) 275 mg and docosahexaenoic acid (DHA) 137 mg; artichoke extract leaves (Altilix®) 150 mg; Citrus bergamia Risso et Poit. dry extract (BPF®) 100 mg; Cynara scolymus L. dry extract 10 mg; olive fruit dry extract standardized to 9% hydroxytyrosol 55.600 mg, corresponding to hydroxytyrosol 5.004 mg; coenzyme Q10 10 mg; folic acid 0.3 mg; and vitamin E 12 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in plasma non-high-density lipoprotein cholesterol (non-HDL-C)	Between-group comparison of the change from baseline in plasma non-HDL-C after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in total cholesterol (TC)	Between-group comparison of the change from baseline in plasma TC after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in low-density lipoprotein cholesterol (LDL-C)	Between-group comparison of the change from baseline in plasma LDL-C after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in triglycerides (TG)	Between-group comparison of the change from baseline in plasma TG after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in high-density lipoprotein cholesterol (HDL-C)	Between-group comparison of the change from baseline in plasma HDL-C after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in very-low-density lipoprotein cholesterol (VLDL-C)	Between-group comparison of the change from baseline in plasma VLDL-C after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in remnant cholesterol	Between-group comparison of the change from baseline in plasma remnant cholesterol after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in fasting plasma glucose	Between-group comparison of the change from baseline in fasting plasma glucose after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in triglyceride-glucose index (TyG index)	Between-group comparison of the change from baseline in TyG index after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in aspartate aminotransferase (AST)	Between-group comparison of the change from baseline in plasma AST after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in alanine aminotransferase (ALT)	Between-group comparison of the change from baseline in plasma ALT after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in gamma-glutamyl transferase (gamma-GT)	Between-group comparison of the change from baseline in plasma gamma-GT after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in hepatic steatosis index (HSI)	Between-group comparison of the change from baseline in HSI after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in fatty liver index (FLI)	Between-group comparison of the change from baseline in FLI after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in uric acid	Between-group comparison of the change from baseline in plasma uric acid after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in high-sensitivity C-reactive protein (hs-CRP)	Between-group comparison of the change from baseline in plasma hs-CRP after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in endothelial reactivity	Between-group comparison of the change from baseline in endothelial reactivity after 8 weeks of double-blind treatment (Cardiol Forte versus placebo). Endothelial reactivity will be assessed by flow-mediated dilation.	Baseline to Week 8 (Day 56 ± 3 days)
Change from baseline in Omega-3 Index	Between-group comparison of the change from baseline in Omega-3 Index after 8 weeks of double-blind treatment (Cardiol Forte versus placebo).	Baseline to Week 8 (Day 56 ± 3 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Week 8 to Week 16 in total cholesterol (TC)	Exploratory evaluation of the change in plasma TC from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in low-density lipoprotein cholesterol (LDL-C)	Exploratory evaluation of the change in plasma LDL-C from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in triglycerides (TG)	Exploratory evaluation of the change in plasma TG from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in high-density lipoprotein cholesterol (HDL-C)	Exploratory evaluation of the change in plasma HDL-C from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in very-low-density lipoprotein cholesterol (VLDL-C)	Exploratory evaluation of the change in plasma VLDL-C from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in remnant cholesterol	Exploratory evaluation of the change in plasma remnant cholesterol from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in fasting plasma glucose	Exploratory evaluation of the change in fasting plasma glucose from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in triglyceride-glucose index (TyG index)	Exploratory evaluation of the change in TyG index from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in aspartate aminotransferase (AST)	Exploratory evaluation of the change in plasma AST from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in alanine aminotransferase (ALT)	Exploratory evaluation of the change in plasma ALT from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in gamma-glutamyl transferase (gamma-GT)	Exploratory evaluation of the change in plasma gamma-GT from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in hepatic steatosis index (HSI)	Exploratory evaluation of the change in HSI from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in fatty liver index (FLI)	Exploratory evaluation of the change in FLI from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in uric acid	Exploratory evaluation of the change in plasma uric acid from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in high-sensitivity C-reactive protein (hs-CRP)	Exploratory evaluation of the change in plasma hs-CRP from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in endothelial reactivity	Exploratory evaluation of the change in endothelial reactivity from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte. Endothelial reactivity will be assessed by flow-mediated dilation.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)
Change from Week 8 to Week 16 in Omega-3 Index	Exploratory evaluation of the change in Omega-3 Index from Week 8 to Week 16 during the open-label extension, when all participants receive Cardiol Forte.	Week 8 to Week 16 (Day 56 ± 3 days to Day 112 ± 3 days)

Collaborators and Investigators

• Sponsor: U.G.A. Nutraceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): May 4, 2026
• Primary Completion (Estimated): May 4, 2028
• Study Completion (Estimated): May 4, 2028

Study Registration Dates

• First Submitted: March 31, 2026
• First Submitted That Met QC Criteria: March 31, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Dyslipidemia; Vitamin E; Folic acid; DHA; Docosahexaenoic acid; Hydroxytyrosol; Coenzyme Q10; EPA; Glycemic profile; Cardiovascular prevention; Eicosapentaenoic acid; non-HDL cholesterol; Bergamot; Cardiol Forte; Low cardiovascular risk; Artichoke
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Nutritional and Metabolic Diseases; Dyslipidemias
• Other Study ID Numbers: CLARISKI_RCT2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No