Nonalcoholic Fatty Liver DiseaseFRUITLESSNCT03067428
Effects of Fructose Restriction on Liver Steatosis
A study testing Glucose and Fructose in people with Nonalcoholic Fatty Liver Disease and Glucose Metabolism Disorders, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Nonalcoholic fatty liver disease (NAFLD) is an emerging health problem as it can lead to end stage liver failure and cardiovascular complications. Diet play an important role in the development of NAFLD. Many studies have addressed the effects of added fructose on NAFLD. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Nonalcoholic Fatty Liver Disease, Glucose Metabolism Disorders, Endothelial Dysfunction
- What is being tested?
- Glucose and Fructose
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteNetherlands
- Study dates
- 31 Jan 2017to 20 Dec 2019
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Body mass index ≥ 28 kg/m2
- Fatty liver index ≥ 60
- Fructose intake ≥45 grams/day
Who cannot join
- Medical history of liver disease
- (History of) excessive alcohol consumption (defined as > 2 units/day for women, and > 3 units/day for men)
- Major change in weight and/or physical activity prior to the study
- Use of glucose lowering drugs
- Recent illness
- Pregnancy and/or lactation
Show all 9Show fewer
- Contraindications for magnetic resonance imaging
- Inability to give informed consent
- Protocol change (implemented on July 18, 2018): in order to increase the inclusion of study participants, subjects with an average daily fructose intake < 45 gram/day will also be eligible for participation. In subjects who have an average daily fructose intake < 45 gram/day, supplementation of either fructose or glucose (see 'Arms and Interventions') will be increased to 45 gram/day.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Center
Maastricht, Limburg, 6200 MD
About this study
Nonalcoholic fatty liver disease (NAFLD) is an emerging health problem as it can lead to end stage liver failure and cardiovascular complications. Diet play an important role in the development of NAFLD. Many studies have addressed the effects of added fructose on NAFLD. To date, little attention has been paid to the effects of a diet devoid of fructose. Therefore, the investigators aim to study the effects of fructose restriction on hepatic fat accumulation and vascular function using a double-blind randomized placebo-controlled design.
- Being tested
- Glucose, Fructose
- Keywords
- Fructose, Diet
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Glucose Metabolism Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlucoseDietary supplement
Participants will adhere to a fructose restricted diet for a period of six weeks (<7.5 grams/meal and/or <10 grams/day; ad-libitum intake). In addition, the amount of fructose that will be restricted - which is based on the average individual fructose intake assessed prior to randomization - will be supplemented as glucose powder three times daily during the meal.
FructoseDietary supplement
Participants will adhere to a fructose restricted diet for a period of six weeks (<7.5 grams/meal and/or <10 grams/day; ad-libitum intake). In addition, the amount of fructose that will be restricted - which is based on the average individual fructose intake assessed prior to randomization - will be supplemented as fructose powder three times daily during the meal.
| Study group | Role | What they receive |
|---|---|---|
| Glucose | Active comparator | Participants will follow a six-week low fructose diet. The amount of restricted fructose will be supplemented as glucose powder. Receives: Dietary Supplement: Glucose |
| Fructose | Placebo comparator | Participants will follow a six-week low fructose diet. The amount of restricted fructose will be supplemented as fructose powder. Receives: Dietary Supplement: Fructose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in intrahepatic triglyceride content
Assessed by magnetic resonance spectroscopy
Measured: 6 weeks
Secondary outcomes (5)
Change in arterial stiffness (PWV)
Assessed by pulse wave velocity
Measured: 6 weeks
Change in endothelial function (flowmotion and skin heating response)
Assessed by laser doppler flowmetry
Measured: 6 weeks
Change in endothelial function (RHI)
Assessed by reactive hyperemia peripheral arterial tonometry
Measured: 6 weeks
Change in endothelial function (panel of endothelial dysfunction biomarkers)
Assessed by plasma biomarkers
Measured: 6 weeks
Change in glucose metabolism
Assessed by a standard 75-gram oral glucose tolerance test
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2017
- Study start31 Jan 2017
- Primary completion20 Dec 2019
- Study completion20 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Nonalcoholic 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double blind, randomized controlled trial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Martijn CG Brouwers, MD,PhD, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03067428
- Sponsor's protocol ID
- 162034
- Acronym
- FRUITLESS
- Status last verified
- Feb 2020
- First submitted
- 21 Feb 2017
- Last updated
- 21 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
van Oeteren MAJ, Simons N, van de Waarenburg MPH, Houben AJHM, Schalkwijk CG, Brouwers MCGJ, Scheijen JLJM. Circulating levels of glucoselysine, a fructose-specific glycation product, are modulated by dietary fructose; post-hoc analysis of a case-control study and a randomized controlled trial. Am J Clin Nutr. 2026 Oct 5:101571. doi: 10.1016/j.ajcnut.2026.101571. Online ahead of print.
PubMed 42833446Chen H, Simons PIHG, Simons N, van de Waarenburg MPH, Bons JAP, van der Ploeg EMC, Feskens EJM, Schalkwijk CG, Brouwers MCGJ. Effects of glucose and fructose supplementation on serum sex hormone-binding globulin and testosterone levels: Post-hoc analysis of a double-blind randomized controlled trial. Clin Nutr ESPEN. 2025 Oct;69:384-388. doi: 10.1016/j.clnesp.2025.07.1123. Epub 2025 Jul 26.
PubMed 40721209Janssen LEF, Simons N, Simons PIHG, Schaper NC, Feskens EJM, van der Ploeg LMC, Van den Eynde MDG, Schalkwijk CG, Houben AJHM, Stehouwer CDA, Brouwers MCGJ. Effects of fructose restriction on blood pressure: Secondary analysis of a double-blind randomized controlled trial. Clin Nutr ESPEN. 2022 Oct;51:97-103. doi: 10.1016/j.clnesp.2022.07.009. Epub 2022 Jul 30.
PubMed 36184254Simons N, Veeraiah P, Simons PIHG, Schaper NC, Kooi ME, Schrauwen-Hinderling VB, Feskens EJM, van der Ploeg EMCL, Van den Eynde MDG, Schalkwijk CG, Stehouwer CDA, Brouwers MCGJ. Effects of fructose restriction on liver steatosis (FRUITLESS); a double-blind randomized controlled trial. Am J Clin Nutr. 2021 Feb 2;113(2):391-400. doi: 10.1093/ajcn/nqaa332.
PubMed 33381794
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Fructose Restriction on Liver Steatosis
- ClinicalTrials.gov ID
- NCT03067428
- Acronym / sponsor ID
- FRUITLESS / 162034
- Keywords
- Fructose, Diet
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- 31 Jan 2017 (actual)
- Primary completion
- 20 Dec 2019 (actual)
- Study completion
- 20 Dec 2019 (actual)
- First posted
- 1 Mar 2017 (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.
Nonalcoholic fatty liver disease (NAFLD) is an emerging health problem as it can lead to end stage liver failure and cardiovascular complications. Diet play an important role in the development of NAFLD. Many studies have addressed the effects of added fructose on NAFLD. To date, little attention has been paid to the effects of a diet devoid of fructose. Therefore, the investigators aim to study the effects of fructose restriction on hepatic fat accumulation and vascular function using a double-blind randomized placebo-controlled design.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- double blind, randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Glucose | Active comparator | Dietary Supplement: GlucoseParticipants will follow a six-week low fructose diet. The amount of restricted fructose will be supplemented as glucose powder. |
| Fructose | Placebo comparator | Dietary Supplement: FructoseParticipants will follow a six-week low fructose diet. The amount of restricted fructose will be supplemented as fructose powder. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥ 18 years
- Body mass index ≥ 28 kg/m2
- Fatty liver index ≥ 60
- Fructose intake ≥45 grams/day
Key exclusion criteria (9 listed)
- Medical history of liver disease
- (History of) excessive alcohol consumption (defined as > 2 units/day for women, and > 3 units/day for men)
- Major change in weight and/or physical activity prior to the study
- Use of glucose lowering drugs
- Recent illness
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 |
|---|---|---|
| GlucoseParticipants will adhere to a fructose restricted diet for a period of six weeks (<7.5 grams/meal and/or <10 grams/day; ad-libitum intake). In addition, the amount of fructose that will be restricted - which is based on the average individual fructose intake assessed prior to randomization - will be supplemented as glucose powder three times daily during the meal. | Dietary supplement | Glucose |
| FructoseParticipants will adhere to a fructose restricted diet for a period of six weeks (<7.5 grams/meal and/or <10 grams/day; ad-libitum intake). In addition, the amount of fructose that will be restricted - which is based on the average individual fructose intake assessed prior to randomization - will be supplemented as fructose powder three times daily during the meal. | Dietary supplement | Fructose |
Primary outcome
Change in intrahepatic triglyceride content
Time frame: 6 weeks
Assessed by magnetic resonance spectroscopy
5 secondary outcomes
Change in arterial stiffness (PWV)
Time frame: 6 weeks
Change in endothelial function (flowmotion and skin heating response)
Time frame: 6 weeks
Change in endothelial function (RHI)
Time frame: 6 weeks
Change in endothelial function (panel of endothelial dysfunction biomarkers)
Time frame: 6 weeks
Change in glucose metabolism
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2020.
- Derived from this study: PubMed 42833446van Oeteren MAJ, Simons N, van de Waarenburg MPH, Houben AJHM, Schalkwijk CG, Brouwers MCGJ, Scheijen JLJM. Circulating levels of glucoselysine, a fructose-specific glycation product, are modulated by dietary fructose; post-hoc analysis of a case-control study and a randomized controlled trial. Am J Clin Nutr. 2026 Oct 5:101571. doi: 10.1016/j.ajcnut.2026.101571. Online ahead of print.
- Derived from this study: PubMed 40721209Chen H, Simons PIHG, Simons N, van de Waarenburg MPH, Bons JAP, van der Ploeg EMC, Feskens EJM, Schalkwijk CG, Brouwers MCGJ. Effects of glucose and fructose supplementation on serum sex hormone-binding globulin and testosterone levels: Post-hoc analysis of a double-blind randomized controlled trial. Clin Nutr ESPEN. 2025 Oct;69:384-388. doi: 10.1016/j.clnesp.2025.07.1123. Epub 2025 Jul 26.
- Derived from this study: PubMed 36184254Janssen LEF, Simons N, Simons PIHG, Schaper NC, Feskens EJM, van der Ploeg LMC, Van den Eynde MDG, Schalkwijk CG, Houben AJHM, Stehouwer CDA, Brouwers MCGJ. Effects of fructose restriction on blood pressure: Secondary analysis of a double-blind randomized controlled trial. Clin Nutr ESPEN. 2022 Oct;51:97-103. doi: 10.1016/j.clnesp.2022.07.009. Epub 2022 Jul 30.
- Derived from this study: PubMed 33381794Simons N, Veeraiah P, Simons PIHG, Schaper NC, Kooi ME, Schrauwen-Hinderling VB, Feskens EJM, van der Ploeg EMCL, Van den Eynde MDG, Schalkwijk CG, Stehouwer CDA, Brouwers MCGJ. Effects of fructose restriction on liver steatosis (FRUITLESS); a double-blind randomized controlled trial. Am J Clin Nutr. 2021 Feb 2;113(2):391-400. doi: 10.1093/ajcn/nqaa332.
- 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.
Martijn CG Brouwers, MD,PhD principal investigator
Maastricht University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Glucose and Fructose in people with Nonalcoholic Fatty Liver Disease and Glucose Metabolism Disorders, 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 9 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: finished, as of the sponsor's last update on 21 Feb 2020. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in intrahepatic triglyceride content (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03067428, which also lists 4 linked publications.
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 21 Feb 2020.