Plant Sterols and Plant Stanols and Liver Inflammation

• ClinicalTrials.gov Identifier: NCT03627819
• Recruitment Status: Unknown
• First Posted: August 13, 2018
• Last Update Posted: August 27, 2018
• Sponsor: Maastricht University Medical Center
• Collaborators: Unilever R&D; Raisio Group; BASF
• Information provided by (Responsible Party): Maastricht University Medical Center

Tracking Information

• First Submitted Date: July 18, 2018
• First Posted Date: August 13, 2018
• Last Update Posted Date: August 27, 2018
• Actual Study Start Date: May 4, 2018
• Estimated Primary Completion Date: October 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 8, 2018)

Biopsy-proven liver inflammation [ Time Frame: 1 year intervention ]

NASH histology

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 23, 2018)

• Hyperinsulinemic-euglycemic clamp [ Time Frame: 1 year intervention ]
  Insulin sensitivity
• Liver fat [ Time Frame: 1 year intervention ]
  Liver fat measured by magnetic resonance spectroscopy (MRS)

Original Secondary Outcome Measures (submitted: August 8, 2018)

• Hyperinsulinemic-euglycemic clamp [ Time Frame: 1 year intervention ]
  Insulin sensitivity
• Liver fat [ Time Frame: 1 year intervention ]
  Liver fat measured by MRS

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Plant Sterols and Plant Stanols and Liver Inflammation
• Official Title: 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

Brief Summary

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

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
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Investigator, Outcomes Assessor)
Masking Description:

The margarine is provided in white but colour-coded tubs and it is not known to the participant and the researcher which colour coded margarine is placebo, plant sterol or stanol ester margarine.

Primary Purpose: Treatment

• Condition: Non-Alcoholic Fatty Liver Disease

Intervention

• Dietary Supplement: Plant sterol-enriched margarine
  Margarine enriched with plant sterol esters
• Dietary Supplement: Plant stanol-enriched margarine
  Margarine enriched with plant stanol esters
• Dietary Supplement: Control margarine
  Margarine without any addition

Study Arms

• 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
  Intervention: Dietary Supplement: Plant sterol-enriched margarine
• 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
  Intervention: Dietary Supplement: Plant stanol-enriched margarine
• Placebo Comparator: Control margarine
  Intake of 20 gram margarine without any addition, every day for 1 year
  Intervention: Dietary Supplement: Control margarine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 8, 2018): 15
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2019
• Estimated Primary Completion Date: October 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT03627819
• Other Study ID Numbers: NASH Pilot Study
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Maastricht University Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Maastricht University Medical Center
• Original Study Sponsor: Same as current

Collaborators

• Unilever R&D
• Raisio Group
• BASF

Investigators

• Study Chair: Jogchum Plat, Prof.; Maastricht University Medical Centre

• PRS Account: Maastricht University Medical Center
• Verification Date: August 2018