Plant Sterols and Plant Stanols and Liver Inflammation

Study Overview
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Brief Summary
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As the prevalence of obesity is reaching epidemic proportions, the prevalence of non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH), increases concomitantly and becomes a major global health hazard. Successful pharmacological interventions to treat or prevent NASH are not available and so far only weight loss has clear benefits, but sustained weight-loss is difficult to achieve on the longer-term. We recently demonstrated in mice that plant sterol and stanol ester consumption inhibited the development of liver inflammation, which needs to be validated in humans in a translational approach. In the current proposed pilot study, the effect of consuming plant sterol or plant stanol esters on biopsy proven liver inflammation will be investigated in NAFLD patients. The objective is to assess the effect of consuming plant sterol or plant stanol esters (3 grams/day) for 12 months on biopsy proven liver inflammation in NAFLD patients. This study is a randomized, placebo-controlled, double blinded pilot study with a run-period of 2 weeks, an intervention period of 12 months and a wash-out period of 1 month. The study population consists of 15 patients with biopsy-proven liver inflammation, aged 18-75 years. All subjects will start a run-in period of two weeks during which they consume daily 20 grams of control margarine after which they will be randomly allocated to consume 20 grams control margarine or plant sterol or plant stanol enriched margarine on a daily basis for a period of 12 months. The primary outcome parameter in this study is biopsy proven liver inflammation.

Detailed Description
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The objective is to assess the effect of consuming plant sterol or plant stanol esters (3 grams/day) for 12 months on biopsy proven liver inflammation in NAFLD patients. This study is a randomized, placebo-controlled, double blinded pilot study with a run-period of 2 weeks, an intervention period of 12 months and a wash-out period of 1 month. The study population consists of 15 patients with biopsy-proven liver inflammation, aged 18-75 years. All subjects will start a run-in period of two weeks during which they consume daily 20 grams of control margarine after which they will be randomly allocated to consume 20 grams control margarine or plant sterol or plant stanol enriched margarine on a daily basis for a period of 12 months. The primary outcome parameter in this study is biopsy proven liver inflammation.

Official Title
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The Effects of Plant Sterol and Plant Stanol Ester Enriched Foods on Biopsy Proven Liver Inflammation in NAFLD Patients - a Proof-of-concept Pilot Study

Conditions
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Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Dietary Supplement: Plant sterol-enriched margarine
* Dietary Supplement: Plant stanol-enriched margarine
* Dietary Supplement: Control margarine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be able to give written informed consent Diagnosed with liver inflammation by a liver biopsy <12 months prior to start of the study. All patients with biopsies older than 2 months must have a stable weight and biochemical liver test results. A certified, experienced pathologist will assess the presence of liver inflammation. No presence of cirrhosis as diagnosed by the liver biopsy or by the FibroScan Aged between 18 and 75 years Body Mass Index (BMI) <40 kg/m2 Willingness to consume 20 grams of margarine on a daily basis for a period of 12 months Exclusion Criteria: Are less than 18 years of age or over 75 years of age Females who are pregnant, breast feeding or who may wish to become pregnant during the study Have a significant acute or chronic coexisting illness such as cardiovascular disease, chronic kidney disease, gastrointestinal disorder, endocrinological disorder, immunological disorder, cancer or any condition which contraindicates, in the investigators judgement, entry to the study Severe medical conditions that might interfere with the study such as epilepsy, asthma, chronic obstructive pulmonary disease, inflammatory bowel disease and rheumatoid arthritis Use of diuretics or insulin therapy Use of anti-coagulants History of illicit drug use Consume more than the recommended alcohol guidelines i.e. >21 alcohol units/week for males and >14 units/week for females Not willing to stop the consumption of plant sterol or plant stanol enriched products 1 month before the start of the study (wash-in period) Use of an investigational product in another biomedical study within the previous month Contraindications for magnetic resonance imaging (MRI)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study is a randomized, placebo-controlled, double blinded pilot study with a run-period of 2 weeks, an intervention period of 12 months and a wash-out period of 1 month.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Plant sterol-enriched margarine<br>Intake of 20 gram margarine with added plant sterol esters, providing 3 gram plant sterols per day for 1 year | Dietary Supplement: Plant sterol-enriched margarine<br>* Margarine enriched with plant sterol esters<br>|
| Active Comparator: Plant stanol-enriched margarine<br>Intake of 20 gram margarine with added plant stanol esters, 3 gram plant stanols per day for 1 year | Dietary Supplement: Plant stanol-enriched margarine<br>* Margarine enriched with plant stanol esters<br>|
| Placebo Comparator: Control margarine<br>Intake of 20 gram margarine without any addition, every day for 1 year | Dietary Supplement: Control margarine<br>* Margarine without any addition<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biopsy-proven liver inflammation | NASH histology | 1 year intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hyperinsulinemic-euglycemic clamp | Insulin sensitivity | 1 year intervention | 
| Liver fat | Liver fat measured by magnetic resonance spectroscopy (MRS) | 1 year intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plant sterols, Plant stanols, Liver inflammation