Red Yeast Rice and Phytosterols In Statin Intolerance

Red Yeast Rice and Phytosterols Versus Red Yeast Rice and Placebo for the Treatment of Hyperlipidemia in Patients With Statin Intolerance: A Multi-Center Randomized Double-blind Study

Red yeast rice may be useful to lower cholesterol, especially in a population of patients who cannot tolerate traditional therapy with statins.

The addition of an over-the-counter phytosterol to red yeast rice may offer additional lipid lowering benefits when compared to red yeast rice alone.

These supplements will be given to all participants. Up to one-half will enroll in a lifestyle intervention program called Change of Heart and will be compared to patients who do not participate in the program. The study will last one year.

Study Overview

• Status: Completed
• Conditions: Hyperlipidemia
• Intervention / Treatment: Drug: placebo; Dietary supplement: red yeast rice; Drug: phytosterol; Behavioral: therapeutic lifestyle program

Detailed Description

Although recent studies have shown that red yeast rice is an effective therapy in the treatment of hyperlipidemia, additional supplements may be required to lower cholesterol to levels that have been associated with decreased coronary events. Specifically a target has been to lower low-density lipoprotein-C (LDL-C) to levels below 100 mg/dl. Red yeast rice has been found to be effective in lowering cholesterol in the context of the Change of Heart Program, where participants are encouraged to make significant lifestyle changes. This has been documented in two recent trials that we have published in the past year in the Mayo Clinic Proceedings (July 2008) and The Annals of Internal Medicine (in press). Clinically, we have found it necessary to add a phytosterol supplement to red yeast rice to lower LDL-C levels below 100 mg/dl. There has been a great deal of interest in phytosterols in both the lay and medical press in the past several years. This over the counter supplement lowers cholesterol by acting in the intestine to decrease the absorption of cholesterol. As it is not absorbed, there have not been any reports of significant side effects. The purpose of this study is to examine the lipid lowering effects of red yeast rice with and without adding a phytosterol. Some participants will attend the Change of Heart Program and take these supplements. Another group of participants will take the same supplements, with their usual medical care, but not enroll in the Change of Heart Program. The study will last one year, and participants will have been intolerant of statins in the past.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Abington, Pennsylvania, United States
      • Abington Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19118
      • Chestnut Hill Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women age > 21
• LDL > 100 and physician suggestion to take statin
• Subject complains of muscle weakness or aching which he/she or his/her physician feels may be attributable to statin therapy
• Having stopped a statin drug for personal reasons and not willing to restart this medication
• Refusal to take a statin as prescribed by personal physician
• CPK < 400
• Not taking any cholesterol lowering medication, red yeast rice extract or a phytosterol product for at least 1 month prior to initiation of trial
• Ability to exercise without physical restrictions
• Ability to attend 12 week consecutive Change of Heart lifestyle education sessions
• Liver function studies normal at baseline
• Subject willing to remain off the dietary supplement CoQ10 for duration of trial
• TSH must be normal

Exclusion Criteria:

• A history of muscle damage (CPK > 400 IU) on statin therapy
• Any active cardiac problem including chest pain, angina, shortness of breath with minimal activity, or unstable angina/acute coronary syndrome within one year
• Known intolerance to one of the study drugs
• Physical limitation preventing aerobic exercise program, such as severe arthritis, peripheral vascular disease, congestive heart failure, or symptom limiting pulmonary disease
• Uncontrolled hypertension (defined as SBP > 180 mmHg or DBP > 100 mmHg
• Heart attack, bypass surgery, or angioplasty/stent within 1 year of study
• Triglyceride level more than 400 mg/dl
• Underlying musculoskeletal disorder preventing muscle testing
• Taking other medicines including: cyclosporine, erythromycin or other macrolide antibiotics; fluconazole; niacin; fibrates; or > 16 oz. of grapefruit juice daily

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: red yeast rice (RYR) plus phytosterol; arm will take red yeast rice and phytosterol supplement	Dietary supplement: red yeast rice; 600 mg 3 capsules bid; Drug: phytosterol; phytosterol 450 mg 2 tabs bid with food
Placebo Comparator: red yeast rice plus placebo	Drug: placebo; placebo; Dietary supplement: red yeast rice; 600 mg 3 capsules bid
Active Comparator: TLC plus red yeast rice plus placebo; subjects attend 12 week therapeutic lifestyle program and take above supplement	Drug: placebo; placebo; Dietary supplement: red yeast rice; 600 mg 3 capsules bid; Behavioral: therapeutic lifestyle program; TLC - 12 weeks
Experimental: TLC plus RYR plus phytosterol; Therapeutic lifestyle program for 12 weeks plus red yeast rice plus phytosterol	Dietary supplement: red yeast rice; 600 mg 3 capsules bid; Drug: phytosterol; phytosterol 450 mg 2 tabs bid with food; Behavioral: therapeutic lifestyle program; TLC - 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
LDL cholesterol levels	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
myalgia compared to prior statin usage	one year
other lipoprotein levels	one year
weight loss in TLC program vs. baseline	one year

Collaborators and Investigators

• Sponsor: Chestnut Hill Health System
• Investigators: Principal Investigator: David J Becker, MD, Chestnut Hill Heathcare

Publications and helpful links

General Publications

• Becker DJ, French B, Morris PB, Silvent E, Gordon RY. Phytosterols, red yeast rice, and lifestyle changes instead of statins: a randomized, double-blinded, placebo-controlled trial. Am Heart J. 2013 Jul;166(1):187-96. doi: 10.1016/j.ahj.2013.03.019. Epub 2013 Apr 30.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: May 11, 2009
• First Submitted That Met QC Criteria: May 11, 2009
• First Posted (Estimate): May 12, 2009

Study Record Updates

• Last Update Posted (Estimate): July 18, 2011
• Last Update Submitted That Met QC Criteria: July 14, 2011
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Keywords: compliance; hyperlipidemia; phytosterols; red yeast rice; statin associated myalgias; therapeutic lifestyle changes
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Hyperlipoproteinemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Red yeast rice
• Other Study ID Numbers: FWA00005390 Chestnut HillHC