Effect of L. Reuteri NCIMB 30242 on Plasma Bile Acid Profile

Study Overview
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Brief Summary
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Background: In recent years, probiotics have shown promise in treating a variety of diseases. Previously, the investigators have reported on the clinical efficacy of bile salt hydrolase active Lactobacillus reuteri NCIMB 30242 in improving the lipid profile in hypercholesterolemic adults. Objective: The purpose of the study is to investigate the effect of a delayed release or standard vegetarian capsule containing L. reuteri NCIMB 30242, taken in escalated dose over a 4 week period, on the plasma bile acid profile. Design: The study design is a pilot, randomized, double-blind, dose-escalation study. The study will last a total of 6 weeks, including a 4-week intervention period and a 2-week washout period.

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Dietary Supplement: Delayed release capsule, L. reuteri NCIMB 30242, escalated dose
* Dietary Supplement: Standard vegetarian capsule, L. reuteri NCIMB 30242, escalated dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, aged 20 to 75 years (bounds included). LDL-C ≥ 3.40 mmol/L. TG < 4.00 mmol/L. TBA < 10 umol/L. BMI range from 23.0 to 32.5 kg/m2 (bounds included). Signed informed consent form prior to inclusion in the study. Note: Subjects will be permitted to take stable doses of thyroid hormone and anti-hypertensive agents, as long as these are continued equivalently throughout the duration of study. Female subjects not of child bearing potential. Defined as females who have had a hysterectomy or oophorectomy, bilateral tubal ligation or are post-menopausal (natural or surgically with > 1 year since last menstruation) OR Female subject of childbearing potential who agree to use a medically approved method of birth control and have a negative urine pregnancy test result. Acceptable methods of birth control include: Hormonal contraceptives including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (Depo-Provera, Lunelle), or hormone implant (Norplant System); Intrauterine devices; Vasectomy of partner; Total abstinence. Exclusion Criteria: Use of cholesterol lowering prescription drugs within the last 6 months. Use of plant sterols, omega 3, fish oil, soy protein, soluble oat fiber, psyllium seed husk, or other cholesterol lowering non-prescription supplements within last 1 month. History of chronic use of alcohol (> 2 drinks/d). History of heavy smoking (≥ 20 cigarettes/d). Use of systemic antibodies, corticosteroids, androgens, or phenytoin. Immune-compromised subjects (e.g. AIDS, lymphoma, subjects undergoing long-term corticosteroid treatment) Subject having experienced any cardiovascular event (Myocardial infarction, coronary artery bypass, or other major surgical procedures) in the last 6 months. Subjects with elevated LDL-C (≥ 3.40 mmol/L) and high (>20%) CVD risk estimated by the Framingham risk score Previously diagnosed Type I or Type II diabetes. Subject receiving systemic treatment or topical treatment likely to interfere with evaluation of the study parameters. Subject currently involved in a clinical trial or in an exclusion period following participation in another clinical trial. History of angina, congestive heart failure, inflammatory bowel disease, pancreatitis, gastrointestinal, renal, pulmonary, hepatic or biliary disease, or cancer (evidence of active lesions, chemotherapy or surgery in the past year). Clinically significant abnormal laboratory results at screening. Chronic user of probiotics or fibre laxative (greater than 2 doses/wk), or stimulant laxatives. History of eating disorders. Exercise greater than 15 miles/wk or 4,000 kcal/wk. Female subjects that are pregnant, breast feeding or intend to get pregnant. Allergy or sensitivity to test product ingredients Allergy or sensitivity to all 3 antibiotics (Clindamycin, Erythromycin and Ampicillin).

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Delayed release capsule, L. reuteri NCIMB 30242<br> | Dietary Supplement: Delayed release capsule, L. reuteri NCIMB 30242, escalated dose<br> <br> |
| Experimental: Standard vegetarian capsule, L. reuteri NCIMB 30242<br> | Dietary Supplement: Standard vegetarian capsule, L. reuteri NCIMB 30242, escalated dose<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome will be the change in plasma bile acid profile from baseline to endpoint |  | Week 0 and Week 4 of intervention period |