Clinical trial NCT03857256: Compare the Efficacy and Safety of Beta-Glucan as Add-On to Statin in Subjects With Hyperlipidemia.
Official title: A Multicenter, Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study To Compare The Efficacy And Safety Of High-Medium Molecular Weight Beta-Glucan As Add-On To Statin Therapy In Subjects With Hyperlipidemia.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hyperlipidemias
Lead sponsor: Montreal Heart Institute
Sponsor class: OTHER
Collaborators: name: Ceapro Inc.
name: The Montreal Health Innovations Coordinating Center (MHICC)
First posted: 2019-02-27
Enrollment: 263
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the effects of adding beta-glucan (1.5 g, 3 g or 6 g daily) administered three times a day (TID) in divided doses, to atorvastatin (10 mg - 20 mg) once a day or an equivalent dose of another statin on heart disease lipid risk factors.

Detailed description: Male and female subjects ≥ 18 years of age with an elevated LDL-C \> 3.37 mmol/L (130 mg/dL) treated with a stable dose of statin for at least 6 weeks (atorvastatin (10-20mg daily) or equivalent dose of another statin), including subject with previous cardiovascular (CV) events, with partial statin intolerance defined as an inability to tolerate statin therapy in the form and dosages required to achieve treatment goals.

Following signature of informed consent, approximately 264 subjects (66 subjects per beta-glucan treatment group and 22 subjects per matching placebo group) meeting all inclusion criteria and no exclusion criteria will be randomized to receive one of the three doses of beta-glucan (1.5 g, 3 g or 6 g daily) administered TID in divided doses or a matching placebo as an add-on therapy to atorvastatin (10- 20 mg administered once daily) or an equivalent dose of another statin.

The subjects will be assigned to the 3 different doses of beta-glucan or placebo in a tiered fashion as follows:

* The first set of 88 subjects randomized will receive either 1.5 g beta-glucan daily (1 tablet of 500 mg TID) or a matching placebo in a 3:1 ratio,
* The next set of 88 subjects randomized will receive either 3 g of beta-glucan daily (2 tablets of 500 mg TID) or a matching placebo in a 3:1 ratio,
* The last set of 88 subjects randomized will receive either 6 g of beta-glucan daily (4 tablets of 500 mg TID) or a matching placebo in a 3:1 ratio.

During the treatment period, subjects will return to the study site at Visit 3 (Week 6) and at the End of Treatment Visit (Week 12) for laboratory tests and clinical assessments, including Adverse Events (AEs), dietary guidance and study product compliance. At the Safety Follow-up Visit (Week 14), subjects will be contacted via telephone for an assessment of AEs.

Eligibility criteria: Inclusion Criteria:

Subjects must meet ALL of the following inclusion criteria in order to be eligible for this study:

1. Male or female ≥18 years of age
2. Subjects with hyperlipidemia treated with stable dose of statin for at least 6 weeks; either atorvastatin (10 mg to 20 mg daily) or equivalent dose of another statin at the time of informed consent and with LDL-C level \>3.37 mmol/L (130 mg/dL) in fasting conditions at screening
3. Subjects willing to maintain stable standard cholesterol lowering diet (Appendix 2) and physical activity level throughout the study
4. Female of childbearing potential must have a negative urine pregnancy test at screening and randomization baseline Visit 2

   Women are considered not of childbearing potential if they:
   1. Have had a hysterectomy, a bilateral oophorectomy or tubal ligation prior to Combination Therapy Baseline Visit.
   2. Are postmenopausal defined as no menses for at least 1 year and have a serum FSH level of 40 IU/L.

   Women of childbearing potential must agree to use an effective method of birth control throughout the study. Acceptable means of birth control include: implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, male or female condoms with spermicide, abstinence, or a sterile sexual partner
5. Ability and willingness to give written informed consent and to comply with the requirements of the study

Exclusion Criteria:

A subject who meets any of the following criteria will NOT be eligible to the study:

1. Use of any other lipid modifying drugs including but not limited to:

   1. Niacin (nicotinic acid) or niacinamide (nicotinamide)
   2. Fibrates or fibric acid derivatives including fenofibrate, gemfibrozil, clofibrate
   3. Bile acid sequestrants including cholestyramine, colesevelam, colestipol
   4. Ezetimibe
   5. PCSK9 inhibitors
   6. Systemic corticosteroids
2. Use of any other lipid modifying supplements within the last 30 days, including but not limited to (a 30-day wash out period is permitted):

   1. Beta-glucan supplements other than the investigational product
   2. Omega-3 fatty acids
   3. Supplements containing flaxseed, fish oil, or algal oil
   4. Sterol/stanol products
   5. Red yeast rice supplements or soy isoflavone supplements
   6. Dietary fiber supplements including \> 2 teaspoonful of Metamucil® or psyllium containing supplements per day
   7. Supplements containing oats, oatmeal and oat bran.
3. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) with the exception of acetylsalicylic acid (ASA) at a concentration of up to 325 mg twice a day
4. BMI ≥ 40 kg/m2
5. Female who is pregnant, planning to become pregnant during the study, or breast feeding
6. Subject who is not willing to keep stable the exercise level during the study
7. History of poorly controlled diabetes within the last 3 months (HbA1C \>10%)
8. Subjects with poorly controlled blood pressure defined as a sustained mean systolic blood pressure 160 or \<100 mmHg and/or diastolic blood pressure 100 or \<60 mmHg at screening
9. History of unstable angina, myocardial infarction, coronary artery bypass graft surgery (CABG), percutaneous coronary intervention (PCI), carotid surgery or stenting, cerebrovascular accident, or transient ischemic attack (TIA) within 6 months prior to screening
10. History of heart failure NYHA III-IV within 12 months prior to screening.
11. Subjects with clinically significant electrocardiographic abnormalities
12. Subjects with history of clinically significant endocrine disease known to influence serum lipids
13. Subjects with evidence of hepatic disease (ALT and/or AST greater than 2X ULN, total bilirubin greater than 1.5X ULN, or cirrhosis) at screening
14. Renal dysfunction defined as glomerular filtration rate (GFR) ≤45 mL/min/1.73 m2 at screening
15. Subjects who suffer from inflammatory bowel disease or irritable bowel syndrome
16. Known allergies or intolerance to oats
17. History of malignancy, except subjects who have been disease-free for \> 3 yrs or resected basal or squamous cell skin carcinoma or cervical carcinoma in situ
18. Consumption of \> 14 alcoholic drinks per week (1 drink = 12 oz beer, 5 oz wine, or 1.5 oz hard liquor at screening). Counseling should be given to encourage the subject to maintain consumption at or below this level throughout the study
19. History of drug abuse
20. Participation in another clinical trial within 30 days of signing the Information and Consent Form (ICF)
21. Any condition or therapy that the investigator believes might pose a risk to the subject or makes participation in the study not in the subject's best interest

Primary outcomes:
measure: Change in Direct-measured LDL-C
timeFrame: week 0 to week 12
Secondary outcomes:
measure: Changes in Total Cholesterol,
timeFrame: week 0 to week 12
measure: Changes in Non-High-density Lipoprotein Cholesterol,
timeFrame: week 0 to week 12
measure: Changes in Small Low-density Lipoprotein Subclass Particle Concentration,
timeFrame: week 0 to week 12
measure: Changes in High Sensitivity C-reactive Protein,
timeFrame: week 0 to week 12
measure: Changes in Very Low-density Lipoprotein Cholesterol,
timeFrame: week 0 to week 12
measure: Changes in Apo B.
timeFrame: week 0 to week 12
Other outcomes:
measure: Changes in HDL-C
timeFrame: week 0 to week 12
measure: Changes in Triglycerides,
timeFrame: week 0 to week 12
measure: Changes in Lipoprotein (a) (Lp(a))
timeFrame: week 0 to week 12
measure: Changes in Glycated Hemoglobin (HbA1c)
timeFrame: week 0 to week 12
Locations:
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
Study officials:
affiliation: Montreal Heart Institute
name: Jean-Claude Tardif, MD
role: PRINCIPAL_INVESTIGATOR
References: