Non-Alcoholic Fatty Liver DiseaseNCT04783116
Plant Stanols and Liver Inflammation in Overweight and Obese Children
A study testing Plant stanols (3g/day) in people with Non-Alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Obesity is associated with a variety of co-morbidities. Children with obesity are more likely to have risk factors associated with cardiovascular diseases (CVD) and CVD risk markers (e.g. Read more about this study
- Who is it for?
- Ages 4 to 18 years
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis, NAFLD
- What is being tested?
- Plant stanols (3g/day)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteNetherlands
- Study dates
- 15 Mar 2021to 31 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Participation in lifestyle intervention, provided by the Centre for Overweight Adolescent and Children Healthcare (COACH), at the Department of Pediatrics at the Maastricht University Medical Center (MUMC+).
- Age between 4-18 years old
- Plasma ALT concentrations above 39 U/L for boys and above 33 U/L for girls.
- Willingness to consume 6 soft chews on a daily basis, for a period of 6 months.
Who cannot join
- Presence of a severe medical condition, which contraindicates, in the investigators judgement, entry to the study.
- No signed informed consent by relevant parties (parents of children aged below 12 years, parents and or children aged between 12 and 16 years, or children aged 16 years and older).
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Center
Maastricht
Anita CE Vreugdenhil, MD, PhD, 0031433875284, a.vreugdenhil@mumc.nl
Judith W Lubrecht, MD, 0031433875284, judith.lubrecht@mumc.nl
About this study
Official title: The Effects of Plant Stanol Ester Supplements on Liver Inflammation in Overweight and Obese Children
Obesity is associated with a variety of co-morbidities. Children with obesity are more likely to have risk factors associated with cardiovascular diseases (CVD) and CVD risk markers (e.g. hypertension, elevated serum cholesterol, and type 2 diabetes mellitus), but also with organ specific pathologies such as a non-alcoholic fatty liver disease (NAFLD). A recent meta-analysis has shown that the prevalence of NAFLD in obese pediatric populations is approximately 35%, compared to approximately 8% in general pediatric population, making it a very important health threat in these populations. Successful pharmacological interventions to treat or prevent NASH are not yet available and so far only weight loss has clear benefits. However, it is well known that sustained weight-loss is difficult to achieve on the longer-term. The investigators recently demonstrated in mice that plant sterol and stanol ester consumption inhibited the development of liver inflammation. Moreover, Javanmardi et al. recently demonstrated in a population of adult NAFLD patients, that plasma concentrations of Alanine Transaminase (ALT) were reduced after daily plant sterol consumption (1.6 g/d) for 6 weeks. In this study, the investigators propose to evaluate the effect of consuming soft chews enriched with plant stanol esters (3 grams/day) on ALT concentrations in children with overweight or (morbid) obesity who are at risk of developing NAFLD, in a randomized, placebo-controlled, double blinded study with an intervention period and follow-up period of 6 months. 52 overweight and obese children with elevated ALT concentrations (>39 U/L for boys and >33 U/L for girls) will be included. All children will be randomly allocated to consume control or plant stanol ester enriched soft chews on a daily basis for a period of 6 months. After 12 months there will be an additional blood sample to evaluate whether the 6 months intervention is still effective.
- Conditions
- Non-Alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis, NAFLD, NASH, NASH - Nonalcoholic Steatohepatitis, Childhood Obesity
- Being tested
- Plant stanols (3g/day), Placebo
- Keywords
- Non-alcoholic Fatty Liver Disease, NAFLD, NASH, Non-alcoholic Steatohepatitis, Liver inflammation, Overweight, Obesity, Adolescents, Children, Lifestyle, Combined lifestyle intervention
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Pediatric Obesity, Hepatitis, Overweight, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plant stanols (3g/day)Dietary supplement
Also called Benecol (Raisio Nutrition Ltd., Raisio, Finland)
Oral consumption of 6 plant stanol enriched chews per day for 6 months (total dosage is 3g/day). Chews are consumed with main meals: two with breakfast, two with lunch and two with dinner.
PlaceboDietary supplement
Oral consumption of 6 placebo chews per day for 6 months. Chews are consumed with main meals: two with breakfast, two with lunch and two with dinner.
| Study group | Role | What they receive |
|---|---|---|
| Plant stanols (3g/day) | Experimental | Consumption of plant stanol chews Receives: Dietary Supplement: Plant stanols (3g/day) |
| Control | Placebo comparator | Consumption of placebo chews (without plant stanols) Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in plasma ALT concentration at 6 and 12 months.
Plasma ALT (Alanine Aminotransferase) concentration is a laboratory parameter, measured in blood, reflecting possible presence of NAFLD. Concentrations below 26 U/L for boys, and below 22 U/L for girls, are considered normal. Concentrations above 39 U/L for boys, and above 33 U/L are considered to reflect presence of NAFLD.
Measured: Baseline, 6 months and 12 months
Secondary outcomes (11)
Change in plasma AST and plasma CK-18 concentration at 6 and 12 months.
Aspartate Aminotransferase (AST) and cytokeratin-18 (CK-18) are laboratory parameters, measured in the participants blood in U/L, reflecting liver health.
Measured: Baseline, 6 months and 12 months
Change in liver inflammation parameters at 6 and 12 months.
Cathepsin-D and acid phosphatase are laboratory parameters, measured in mg/L in the participants blood, reflecting liver inflammation.
Measured: Baseline, 6 months and 12 months
Change in lipid metabolism parameters at 6 and 12 months.
Serum total cholesterol, HDL cholesterol, triacylglycerol (TAG) with correction for free glycerol and non-esterified fatty acids (NEFA) are laboratory parameters, measured in mmol/L in the participants blood, reflecting their lipid metabolism.
Measured: Baseline, 6 months and 12 months
Change in lipid protein metabolism parameters at 6 and 12 months.
ApoA1 and apoB100 plasma concentrations are laboratory parameters, measured in g/L in the participants blood, reflective of the lipoprotein metabolism.
Measured: Baseline, 6 months and 12 months
Change in plasma glucose concentration at 6 and 12 months.
Fasting glucose is a laboratory parameter, measured in mmol/L in the participants blood, reflecting glucose metabolism.
Measured: Baseline, 6 months and 12 months
Change in plasma insulin concentration at 6 and 12 months.
Fasting insulin concentrations is a laboratory parameters, measured in mU/L in the participants blood, reflecting glucose metabolism.
Measured: Baseline, 6 months and 12 months
Change in insulin sensitivity at 6 and 12 months.
Insulin sensitivity will be calculated using the HOMA-IR formula (homeostatis model) which is (fasting glucose*fasting insulin) /22,5. As HOMA-IR is a ratio, it does not have a unit.
Measured: Baseline, 6 months and 12 months
Change in non-cholesterol sterol and oxy(phyto)sterol concentrations at 6 and 12 months.
A panel of non-cholesterol sterols, as surrogate markers for cholesterol absorption and synthesis will be measured in the participants blood.
Measured: Baseline, 6 months and 12 months
Change in plasma inflammatory markers at 6 and 12 months.
Plasma concentrations of CRP and high sensitivity CRP will be measured in mg/L in the participants blood, to assess presence of low-grade inflammation in the body.
Measured: Baseline, 6 months and 12 months
Change in ultrasonographic hepatorenal index (HRI) at 6 and 12 months.
HRI is measured during a conventional ultrasound of the liver, in which three close-up images of the liver and right kidney are made by a physician-researcher. HRI is calculated from these images by a pediatric radiologist, as the ratio of the hepatic brightness and the renal brightness (HRI = echogenicity of the liver/echogenicity of the kidney). The average of the three images is taken as the definite HRI, as a reflection of hepatic fat content.
Measured: Baseline, 6 months and 12 months
Change in continuous Controlled Attenuation Parameter (CAP) at 6 and 12 months.
CAP is measured during a vibration controlled transient elastography of the liver, which is performed with a Fibroscan by a physician-researcher. The value is a reflection of hepatic fat content.
Measured: Baseline, 6 months and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2021
- Study start15 Mar 2021 (estimated)
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04783116
- Sponsor's protocol ID
- NL73527.000.20
- Status last verified
- Mar 2021
- First submitted
- 23 Feb 2021
- Last updated
- 5 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Plant Stanol Ester Supplements on Liver Inflammation in Overweight and Obese Children
- ClinicalTrials.gov ID
- NCT04783116
- Acronym / sponsor ID
- NL73527.000.20
- Conditions
- Non-Alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis, NAFLD, NASH, NASH - Nonalcoholic Steatohepatitis, Childhood Obesity
- Keywords
- Non-alcoholic Fatty Liver Disease, NAFLD, NASH, Non-alcoholic Steatohepatitis, Liver inflammation, Overweight, Obesity, Adolescents
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- 15 Mar 2021 (estimated)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 5 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Obesity is associated with a variety of co-morbidities. Children with obesity are more likely to have risk factors associated with cardiovascular diseases (CVD) and CVD risk markers (e.g. hypertension, elevated serum cholesterol, and type 2 diabetes mellitus), but also with organ specific pathologies such as a non-alcoholic fatty liver disease (NAFLD). A recent meta-analysis has shown that the prevalence of NAFLD in obese pediatric populations is approximately 35%, compared to approximately 8% in general pediatric population, making it a very important health threat in these populations. Successful pharmacological interventions to treat or prevent NASH are not yet available and so far only weight loss has clear benefits. However, it is well known that sustained weight-loss is difficult to achieve on the longer-term. The investigators recently demonstrated in mice that plant sterol and stanol ester consumption inhibited the development of liver inflammation. Moreover, Javanmardi et al. recently demonstrated in a population of adult NAFLD patients, that plasma concentrations of Alanine Transaminase (ALT) were reduced after daily plant sterol consumption (1.6 g/d) for 6 weeks. In this study, the investigators propose to evaluate the effect of consuming soft chews enriched with plant stanol esters (3 grams/day) on ALT concentrations in children with overweight or (morbid) obesity who are at risk of developing NAFLD, in a randomized, placebo-controlled, double blinded study with an intervention period and follow-up period of 6 months. 52 overweight and obese children with elevated ALT concentrations (>39 U/L for boys and >33 U/L for girls) will be included. All children will be randomly allocated to consume control or plant stanol ester enriched soft chews on a daily basis for a period of 6 months. After 12 months there will be an additional blood sample to evaluate whether the 6 months intervention is still effective.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Plant stanols (3g/day) | Experimental | Dietary Supplement: Plant stanols (3g/day)Consumption of plant stanol chews |
| Control | Placebo comparator | Dietary Supplement: PlaceboConsumption of placebo chews (without plant stanols) |
Who may qualify
- Ages
- 4 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Participation in lifestyle intervention, provided by the Centre for Overweight Adolescent and Children Healthcare (COACH), at the Department of Pediatrics at the Maastricht University Medical Center (MUMC+).
- Age between 4-18 years old
- Plasma ALT concentrations above 39 U/L for boys and above 33 U/L for girls.
- Willingness to consume 6 soft chews on a daily basis, for a period of 6 months.
Key exclusion criteria (2 listed)
- Presence of a severe medical condition, which contraindicates, in the investigators judgement, entry to the study.
- No signed informed consent by relevant parties (parents of children aged below 12 years, parents and or children aged between 12 and 16 years, or children aged 16 years and older).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Plant stanols (3g/day)Also: Benecol (Raisio Nutrition Ltd., Raisio, Finland)Oral consumption of 6 plant stanol enriched chews per day for 6 months (total dosage is 3g/day). Chews are consumed with main meals: two with breakfast, two with lunch and two with dinner. | Dietary supplement | Plant stanols (3g/day) |
| PlaceboOral consumption of 6 placebo chews per day for 6 months. Chews are consumed with main meals: two with breakfast, two with lunch and two with dinner. | Dietary supplement | Control |
Primary outcome
Change in plasma ALT concentration at 6 and 12 months.
Time frame: Baseline, 6 months and 12 months
Plasma ALT (Alanine Aminotransferase) concentration is a laboratory parameter, measured in blood, reflecting possible presence of NAFLD. Concentrations below 26 U/L for boys, and below 22 U/L for girls, are considered normal. Concentrations above 39 U/L for boys, and above 33 U/L are considered to reflect presence of NAFLD.
11 secondary outcomes
Change in plasma AST and plasma CK-18 concentration at 6 and 12 months.
Time frame: Baseline, 6 months and 12 months
Change in liver inflammation parameters at 6 and 12 months.
Time frame: Baseline, 6 months and 12 months
Change in lipid metabolism parameters at 6 and 12 months.
Time frame: Baseline, 6 months and 12 months
Change in lipid protein metabolism parameters at 6 and 12 months.
Time frame: Baseline, 6 months and 12 months
Change in plasma glucose concentration at 6 and 12 months.
Time frame: Baseline, 6 months and 12 months
Change in plasma insulin concentration at 6 and 12 months.
Time frame: Baseline, 6 months and 12 months
Change in insulin sensitivity at 6 and 12 months.
Time frame: Baseline, 6 months and 12 months
Change in non-cholesterol sterol and oxy(phyto)sterol concentrations at 6 and 12 months.
Time frame: Baseline, 6 months and 12 months
Change in plasma inflammatory markers at 6 and 12 months.
Time frame: Baseline, 6 months and 12 months
Change in ultrasonographic hepatorenal index (HRI) at 6 and 12 months.
Time frame: Baseline, 6 months and 12 months
Change in continuous Controlled Attenuation Parameter (CAP) at 6 and 12 months.
Time frame: Baseline, 6 months and 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Plant stanols (3g/day) in people with Non-Alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anita CE Vreugdenhil, MD, PhD (0031433875284, a.vreugdenhil@mumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in plasma ALT concentration at 6 and 12 months. (time frame: Baseline, 6 months and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2021.