Clinical trial NCT03627819: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Non-Alcoholic Fatty Liver Disease
Keywords: Plant sterols
Plant stanols
Liver inflammation
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Unilever R&D
name: Raisio Group
name: BASF
First posted: 2018-08-13
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Biopsy-proven liver inflammation
timeFrame: 1 year intervention
Secondary outcomes:
measure: Hyperinsulinemic-euglycemic clamp
timeFrame: 1 year intervention
measure: Liver fat
timeFrame: 1 year intervention
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
state: Limburg
Study officials:
affiliation: Maastricht University Medical Centre
name: Jogchum Plat, Prof.
role: STUDY_CHAIR
References: