Supplements, Placebo, or Rosuvastatin Study | NCT04846231

NCT04846231

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
AstraZeneca	INDUSTRY

Description Module

Detailed Description

Few well-controlled trials have studied the LDL-lowering effects of dozens of marketed "cholesterol health" dietary supplements. Prior research suggests most U.S. consumers believe cholesterol health supplements are safer than statins, and a majority of the public also believe supplements are as effective, or more effective, than prescription statins. Approximately one third of US adults who have been told they have elevated cholesterol are using a supplement to provide heart health protection rather than a statin. This represents a significant public health concern.

The purpose of this study is to evaluate the effect of select dietary supplements on cholesterol health compared with a low dose of a statin.

The study is comparing their effect on LDL and HDL cholesterol and inflammatory markers.

A randomized, single blind study design will be used to evaluate rosuvastatin 5 mg. vs. placebo and 6 commercially available over the counter supplements in a hierarchical testing order. Each participant will take study medication/supplement for a total of 4 weeks.

The study will randomize primary prevention patients who are considered borderline and intermediate risk for ASCVD based upon the 2018 Cholesterol Treatment Guidelines7 and are not taking any of the studied medication/supplements at the time of randomization.

Participants must have a documented elevated LDL cholesterol level between 70-189mg/dL, must not currently be taking a statin or one of the dietary supplements included in the trial. Participants willing to discontinue a prohibited supplement for 4 weeks prior to enrollment will be allowed to participate. Study medication will be provided at no charge. There will be 2 visits which include a lab draw at any Cleveland Clinic laboratory. Participants will be randomized (like a coin flip) to be in one of 8 possible groups: Rosuvastatin, Fish oil, Cinnamon, Garlic, Turmeric, Plant sterol, Red yeast rice, or placebo. The study will enroll 200 participants.

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Rosuvastatin	Active Comparator	5 mg once per day	Drug: Rosuvastatin
Placebo	Placebo Comparator	comparable to rosuvastatin 5 mg once per day	Other: Placebo
Fish Oil	Active Comparator	Nature Made 2 soft gels per day	Dietary Supplement: Fish Oil, Cinnamon, Garlique,Turmeric, Plant Sterol, Red Yeast Rice
Cinnamon	Active Comparator	1200mg, 2 capsules per day	Dietary Supplement: Fish Oil, Cinnamon, Garlique,Turmeric, Plant Sterol, Red Yeast Rice
Garlique	Active Comparator	Manufactured by Focus Consumer Health Marketgate,1 tablet per day	Dietary Supplement: Fish Oil, Cinnamon, Garlique,Turmeric, Plant Sterol, Red Yeast Rice
Turmeric	Active Comparator	Bio Schwartz Turmeric Curcumin 1500 mg, 3 capsules per day

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Fish Oil, Cinnamon, Garlique,Turmeric, Plant Sterol, Red Yeast Rice	Dietary Supplement	Subjects will be randomized to a Statin (Rosuvastatin 5 mg), a placebo, or a dietary supplement (Fish oil, Cinnamon, Garlic, Turmeric, Plant sterol, Red yeast rice).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Change in LDL-C From Baseline for Rosuvastatin 5mg Daily Compared With Placebo and Each Dietary Supplement.	The primary objective of this study is to compare the LDL lowering of rosuvastatin with the effect of six commonly used dietary supplements on cholesterol health.	The percent change in LDL-C for rosuvastatin 5 mg compared with dietary supplements after 4 weeks

Secondary Outcomes

Measure	Description	Time Frame
Percent Change in hsCRP for Rosuvastatin vs Dietary Supplements.	Assess the effect of each supplement on inflammatory markers compared with rosuvastatin 5 mg.	The percent change in high sensitivity C reactive protein (hsCRP) for rosuvastatin 5 mg and dietary supplements compared with placebo after 4 weeks.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Written informed consent must be obtained before any assessment is performed.
U.S. adults with primary hypercholesterolemia, 40-75 years of age.
Not currently taking statins or one of the dietary supplements included in the trial. Patients willing to discontinue a prohibited supplement for 4 weeks prior to enrollment will be allowed to participate.
LDL-cholesterol between 70 and 189 mg/dL.
Patients without diabetes mellitus and a 10-year risk of ASCVD between 5 and <20% using the pooled cohort risk equation. * Or Patients with diabetes mellitus in females 50-60 years of age or males 40-50 years of age with an LDL-C between 70-189 mg/dL and with an ASCVD risk below 20%.

Exclusion Criteria:

Age < 40 or >75 years of age
Women who are pregnant, plan to become pregnant within the next 6 months, or are breastfeeding.
Documented liver dysfunction or history of elevated LFTs indicating active liver disease
Documented chronic renal dysfunction within the past two years defined as an eGFR<30mL/min/m2.
Known hypersensitivity to rosuvastatin or any supplement under investigation (i.e. shellfish allergy, etc.).
Currently taking any prescription statin, or other prescription medication/supplements to treat elevated cholesterol or triglycerides.
Currently taking a medication/supplement that has known interaction with rosuvastatin, including fenofibrate, gemfibrozil, HIV medications, colchicine, cyclosporine, warfarin, anti-viral medications to treat Hepatitis C, regorafenib, and darolutamide.
Are unwilling to discontinue prohibited dietary supplement(s) for 4 weeks prior to participation or during the course of the trial. Other non-prohibited supplements will be permitted if doses have been stable for at least 4 weeks.
Known cardiovascular disease including a history of prior MI, stroke/TIA, PAD or prior revascularization procedures of the heart or vasculature (e.g. CABG, stenting, PCI etc.).
Fasting Triglycerides >200mg/dl.
In the opinion of the investigator, any other condition that will preclude participation in the study.

Name	Affiliation	Role
Luke Laffin, M.D.	The Cleveland Clinic	Principal Investigator
Steven Nissen, M.D.	The Cleveland Clinic	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Cleveland Clinic		Cleveland	Ohio	44195	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
36351465	Derived	Laffin LJ, Bruemmer D, Garcia M, Brennan DM, McErlean E, Jacoby DS, Michos ED, Ridker PM, Wang TY, Watson KE, Hutchinson HG, Nissen SE. Comparative Effects of Low-Dose Rosuvastatin, Placebo, and Dietary Supplements on Lipids and Inflammatory Biomarkers. J Am Coll Cardiol. 2023 Jan 3;81(1):1-12. doi: 10.1016/j.jacc.2022.10.013. Epub 2022 Nov 6.

Arm/Group Information

ID	Title	Description
FG000	Rosuvastatin	5 mg once per day Rosuvastatin: Subjects will be randomized to a Statin (Rosuvastatin 5 mg), a placebo, or a dietary supplement (Fish oil, Cinnamon, Garlic, Turmeric, Plant sterol, Red yeast rice).
FG001	Placebo	comparable to rosuvastatin 5 mg once per day Placebo: Subjects will be randomized to a Statin (Rosuvastatin 5 mg), a placebo, or a dietary supplement (Fish oil, Cinnamon, Garlic, Turmeric, Plant sterol, Red yeast rice).
FG002	Fish Oil	Nature Made 2 soft gels per day Fish Oil, Cinnamon, Garlique,Turmeric, Plant Sterol, Red Yeast Rice: Subjects will be randomized to a Statin (Rosuvastatin 5 mg), a placebo, or a dietary supplement (Fish oil, Cinnamon, Garlic, Turmeric, Plant sterol, Red yeast rice).
FG003	Cinnamon	1200mg, 2 capsules per day Fish Oil, Cinnamon, Garlique,Turmeric, Plant Sterol, Red Yeast Rice: Subjects will be randomized to a Statin (Rosuvastatin 5 mg), a placebo, or a dietary supplement (Fish oil, Cinnamon, Garlic, Turmeric, Plant sterol, Red yeast rice).
FG004	Garlique	Manufactured by Focus Consumer Health Marketgate,1 tablet per day Fish Oil, Cinnamon, Garlique,Turmeric, Plant Sterol, Red Yeast Rice: Subjects will be randomized to a Statin (Rosuvastatin 5 mg), a placebo, or a dietary supplement (Fish oil, Cinnamon, Garlic, Turmeric, Plant sterol, Red yeast rice).
FG005	Turmeric	Bio Schwartz Turmeric Curcumin 1500 mg, 3 capsules per day Fish Oil, Cinnamon, Garlique,Turmeric, Plant Sterol, Red Yeast Rice: Subjects will be randomized to a Statin (Rosuvastatin 5 mg), a placebo, or a dietary supplement (Fish oil, Cinnamon, Garlic, Turmeric, Plant sterol, Red yeast rice).
FG006	Plant Sterol	Nature Made CholestOff Plus, 2 soft gels twice a day Fish Oil, Cinnamon, Garlique,Turmeric, Plant Sterol, Red Yeast Rice: Subjects will be randomized to a Statin (Rosuvastatin 5 mg), a placebo, or a dietary supplement (Fish oil, Cinnamon, Garlic, Turmeric, Plant sterol, Red yeast rice).
FG007	Red Yeast Rice	Arazo Nutrition 1200 mg, 2 capsules per day Fish Oil, Cinnamon, Garlique,Turmeric, Plant Sterol, Red Yeast Rice: Subjects will be randomized to a Statin (Rosuvastatin 5 mg), a placebo, or a dietary supplement (Fish oil, Cinnamon, Garlic, Turmeric, Plant sterol, Red yeast rice).

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Rosuvastatin	5 mg once per day Rosuvastatin: Subjects will be randomized to a Statin (Rosuvastatin 5 mg), a placebo, or a dietary supplement (Fish oil, Cinnamon, Garlic, Turmeric, Plant sterol, Red yeast rice).
BG001	Placebo

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percent Change in LDL-C From Baseline for Rosuvastatin 5mg Daily Compared With Placebo and Each Dietary Supplement.

The primary objective of this study is to compare the LDL lowering of rosuvastatin with the effect of six commonly used dietary supplements on cholesterol health.

Posted

Least Squares Mean

95% Confidence Interval

percent change LDL-C

The percent change in LDL-C for rosuvastatin 5 mg compared with dietary supplements after 4 weeks

ID	Title	Description
OG000	Rosuvastatin	5 mg once per day Rosuvastatin: Subjects will be randomized to a Statin (Rosuvastatin 5 mg), a placebo, or a dietary supplement (Fish oil, Cinnamon, Garlic, Turmeric, Plant sterol, Red yeast rice).
OG001	Placebo

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Rosuvastatin	5 mg once per day Rosuvastatin: Subjects will be randomized to a Statin (Rosuvastatin 5 mg), a placebo, or a dietary supplement (Fish oil, Cinnamon, Garlic, Turmeric, Plant sterol, Red yeast rice).

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 23, 2021	Mar 21, 2023	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Jan 12, 2022	Mar 21, 2023	SAP_001.pdf

ID	Term
D006949	Hyperlipidemias
D050171	Dyslipidemias
D052439	Lipid Metabolism Disorders
D008659	Metabolic Diseases

ID	Term
D005395	Fish Oils
D003474	Curcumin
D010840	Phytosterols
C117343	red yeast rice
D000068718	Rosuvastatin Calcium

ID	Term
D009821	Oils
D008055	Lipids
D036381	Diarylheptanoids
D006536	Heptanes
D000473