Plant Sterols and Plant Stanols and Liver Inflammation

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

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.

Study Overview

• Status: Unknown
• Conditions: Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: Plant sterol-enriched margarine; Dietary supplement: Plant stanol-enriched margarine; Dietary supplement: Control margarine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sabine Baumgartner, Dr.; Phone Number: 043-3881305; Email: sabine.baumgartner@maastrichtuniversity.nl

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 ER
      • Recruiting
      • Maastricht University Medical Centre
      • Contact: Sabine Baumgartner, Dr.; Phone Number: +31 (0)43 3881305; Email: sabine.baumgartner@maastrichtuniversity.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Be able to give written informed consent
2. 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.
3. No presence of cirrhosis as diagnosed by the liver biopsy or by the FibroScan
4. Aged between 18 and 75 years
5. Body Mass Index (BMI) <40 kg/m2
6. Willingness to consume 20 grams of margarine on a daily basis for a period of 12 months

Exclusion Criteria:

1. Are less than 18 years of age or over 75 years of age
2. Females who are pregnant, breast feeding or who may wish to become pregnant during the study
3. 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
4. Severe medical conditions that might interfere with the study such as epilepsy, asthma, chronic obstructive pulmonary disease, inflammatory bowel disease and rheumatoid arthritis
5. Use of diuretics or insulin therapy
6. Use of anti-coagulants
7. History of illicit drug use
8. Consume more than the recommended alcohol guidelines i.e. >21 alcohol units/week for males and >14 units/week for females
9. 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)
10. Use of an investigational product in another biomedical study within the previous month
11. Contraindications for magnetic resonance imaging (MRI)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Plant sterol-enriched margarine; 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; Margarine enriched with plant sterol esters
Active Comparator: Plant stanol-enriched margarine; 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; Margarine enriched with plant stanol esters
Placebo Comparator: Control margarine; Intake of 20 gram margarine without any addition, every day for 1 year	Dietary supplement: Control margarine; Margarine without any addition

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Unilever R&D; Raisio Group; BASF
• Investigators: Study Chair: Jogchum Plat, Prof., Maastricht University Medical Centre

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2018
• Primary Completion (Anticipated): October 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: July 18, 2018
• First Submitted That Met QC Criteria: August 8, 2018
• First Posted (Actual): August 13, 2018

Study Record Updates

• Last Update Posted (Actual): August 27, 2018
• Last Update Submitted That Met QC Criteria: August 23, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Plant stanols; Plant sterols; Liver inflammation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Inflammation; Hepatitis; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: NASH Pilot Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No