Fatty Liver, NonalcoholicNCT03593343
Hepatic Glycogen and Fat Oxidation
A study testing Overnight fasting duration in people with Fatty Liver, Nonalcoholic and Meal Time, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Excessive fat in the liver is associated with impairments in metabolic health. Low levels of DNL and high levels of hepatic fat oxidation are considered to be protective. A decrease in glycogen stores has been causally linked to improved whole body fat oxidation. Read more about this study
- Who is it for?
- Ages 45 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Fatty Liver, Nonalcoholic, Meal Time, Fasting
- What is being tested?
- Overnight fasting duration
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteNetherlands
- Study dates
- 8 Jan 2019to 13 Jan 2020
- 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 45 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Signed informed consent
- Caucasian (people will be excluded when having a ≥50% racial African/Asian background)
- Male or postmenopausal female
- Aged 45-75 years at start of the study
- Body mass index (BMI) 27 - 38 kg/m2
- Stable dietary habits (no weight loss or gain >3kg in the past 3 months)
- Sedentary lifestyle (not more than 2 hours of sports per week)
- Liver fat ≥5% as determined by 1H-MRS
Who cannot join
- Type 2 diabetes
- Active diseases (cardiovascular, diabetes, liver, kidney, cancer or other)
- Contra-indication for MRI (which can be found in appendix II)
- Alcohol consumption of >2 servings per day
- Regular smoking (>5 cigarettes per day)
- No use of medication interfering with investigated study parameters (as determined by responsible physician)
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Center
Maastricht, Limburg, 6229 ER
About this study
Official title: The Effect of Modulating Hepatic Glycogen Content on Hepatic Fat Oxidation
Excessive fat in the liver is associated with impairments in metabolic health. Low levels of DNL and high levels of hepatic fat oxidation are considered to be protective.
A decrease in glycogen stores has been causally linked to improved whole body fat oxidation. Also on an organ level, it is suggested that hepatic fat oxidation is stimulated by low hepatic glycogen stores. Next to hepatic fat oxidation, DNL may be influenced by hepatic glycogen stores. Some studies have shown that prolongation of fasting time lowers hepatic glycogen content. It is therefore hypothesized that prolonging fasting time will lower glycogen content and thereby increases fat oxidation and decreases DNL in the liver. To this end, hepatic fat oxidation (plasma marker beta-hydroxybutyrate), de novo lipogenesis, hepatic glycogen content and intrahepatic fat content, will be measured upon a short overnight fast and an extended overnight fast in 13 overweight/obese subjects with hepatic steatosis.
Read the detailed description
Rationale:
Excessive fat in the liver is associated with impairments in metabolic health. Hepatic lipid storage can originate from several metabolic pathways, including de novo lipogenesis (DNL). On the other hand, there are several metabolic pathways that can decrease hepatic fat storage, such as hepatic fat oxidation. Therefore, low levels of DNL and high levels of hepatic fat oxidation are considered to be protective.
A decrease in glycogen stores has been causally linked to improved whole body fat oxidation. Also on an organ level, it is suggested that hepatic fat oxidation is stimulated by low hepatic glycogen stores. Furthermore, whole body glycogen levels were also linked to DNL and in situations with increased whole body glycogen levels in animal models rates of DNL were also high. Therefore, next to hepatic fat oxidation, DNL may be influenced by hepatic glycogen stores.
Some studies have shown that prolongation of fasting time lowers hepatic glycogen content. It is therefore hypothesized that prolonging fasting time will lower glycogen content and thereby increases fat oxidation and decreases DNL in the liver.
Objective:
The primary objective of this study is to investigate to what extent hepatic fat oxidation can be stimulated by lowering hepatic glycogen content during a prolonged overnight fast.
The secondary objective is to investigate whether reductions in hepatic glycogen content are also accompanied by a decrease in DNL. In addition, the metabolic response to a meal (metabolites related to energy metabolism and substrate oxidation) will be studied upon prolonged overnight fasting. Finally, it will be studied whether reducing hepatic glycogen content by prolonged overnight fasting during a few consecutive days lowers intrahepatic fat storage and changes hepatic fat composition.
Study design:
This is a randomized cross-over study.
Study population:
Thirteen healthy overweight/obese males and postmenopausal females, aged between 45-75 years and BMI between 27-38 kg/m2, with liver fat content ≥ 5% will participate in the study. To be able to include enough people with a liver fat content ≥5%, around 27 participants are expected to be screened for liver fat. When liver fat content is <5%, participants will not be included in the study after determination of liver fat content.
Main study parameters/endpoints:
The primary study outcome is hepatic fat oxidation measured as plasma beta-hydroxybutyrate (BHB) levels, which will be measured before and after one night adherence to the fasting protocols. The secondary study outcome is DNL as determined by stable isotope techniques and will also be measured after one night adherence to the fasting protocols. Other study outcomes include hepatic glycogen content, substrate oxidation and plasma metabolites related to energy metabolism (measured before and after one night adherence to the fasting protocols) and intrahepatic fat content and composition (measured after 6 days of adherence to the fasting protocols).
- Conditions
- Fatty Liver, Nonalcoholic, Meal Time, Fasting, Glycogen Depletion
- Being tested
- Overnight fasting duration
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Fasting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Overnight fasting durationBehavioural
Subjects will adhere to overnight fasting protocol for 6 days
| Study group | Role | What they receive |
|---|---|---|
| Short overnight fast | Experimental | Overnight fasting duration intervention: Participants will receive their last evening meal at 11 pm and stay overnight fasted afterwards for (9.5h). Receives: Behavioral: Overnight fasting duration |
| Long overnight fast | Experimental | Overnight fasting duration intervention: Participants will receive their last evening meal at 4.30 pm and stay overnight fasted afterwards for (16h). Receives: Behavioral: Overnight fasting duration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic fat oxidation
measured as plasma BHB levels
Measured: 5 hours
Secondary outcomes (1)
De novo lipogenesis (DNL)
measured as percentage of palmitate in VLDL-TG originating from DNL
Measured: 20 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2018
- Study start8 Jan 2019
- Primary completion8 Jan 2020
- Study completion13 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fatty Liver, NonalcoholicStudies of the same condition, open and under way.
- 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Unilever R&D
- Responsible party
- Sponsor
- Investigators
- Vera Schrauwen-Hinderling, Dr, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03593343
- Sponsor's protocol ID
- NL66264.068.18
- Status last verified
- Oct 2020
- First submitted
- 10 Jul 2018
- Last updated
- 5 Oct 2020
- Results posted
- No
- 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 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Modulating Hepatic Glycogen Content on Hepatic Fat Oxidation
- ClinicalTrials.gov ID
- NCT03593343
- Acronym / sponsor ID
- NL66264.068.18
- Conditions
- Fatty Liver, Nonalcoholic, Meal Time, Fasting, Glycogen Depletion
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Unilever R&D
- Study start
- 8 Jan 2019 (actual)
- Primary completion
- 8 Jan 2020 (actual)
- Study completion
- 13 Jan 2020 (actual)
- First posted
- 20 Jul 2018 (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.
Excessive fat in the liver is associated with impairments in metabolic health. Low levels of DNL and high levels of hepatic fat oxidation are considered to be protective.
A decrease in glycogen stores has been causally linked to improved whole body fat oxidation. Also on an organ level, it is suggested that hepatic fat oxidation is stimulated by low hepatic glycogen stores. Next to hepatic fat oxidation, DNL may be influenced by hepatic glycogen stores. Some studies have shown that prolongation of fasting time lowers hepatic glycogen content. It is therefore hypothesized that prolonging fasting time will lower glycogen content and thereby increases fat oxidation and decreases DNL in the liver. To this end, hepatic fat oxidation (plasma marker beta-hydroxybutyrate), de novo lipogenesis, hepatic glycogen content and intrahepatic fat content, will be measured upon a short overnight fast and an extended overnight fast in 13 overweight/obese subjects with hepatic steatosis.
Detailed description
Rationale:
Excessive fat in the liver is associated with impairments in metabolic health. Hepatic lipid storage can originate from several metabolic pathways, including de novo lipogenesis (DNL). On the other hand, there are several metabolic pathways that can decrease hepatic fat storage, such as hepatic fat oxidation. Therefore, low levels of DNL and high levels of hepatic fat oxidation are considered to be protective.
A decrease in glycogen stores has been causally linked to improved whole body fat oxidation. Also on an organ level, it is suggested that hepatic fat oxidation is stimulated by low hepatic glycogen stores. Furthermore, whole body glycogen levels were also linked to DNL and in situations with increased whole body glycogen levels in animal models rates of DNL were also high. Therefore, next to hepatic fat oxidation, DNL may be influenced by hepatic glycogen stores.
Some studies have shown that prolongation of fasting time lowers hepatic glycogen content. It is therefore hypothesized that prolonging fasting time will lower glycogen content and thereby increases fat oxidation and decreases DNL in the liver.
Objective:
The primary objective of this study is to investigate to what extent hepatic fat oxidation can be stimulated by lowering hepatic glycogen content during a prolonged overnight fast.
The secondary objective is to investigate whether reductions in hepatic glycogen content are also accompanied by a decrease in DNL. In addition, the metabolic response to a meal (metabolites related to energy metabolism and substrate oxidation) will be studied upon prolonged overnight fasting. Finally, it will be studied whether reducing hepatic glycogen content by prolonged overnight fasting during a few consecutive days lowers intrahepatic fat storage and changes hepatic fat composition.
Study design:
This is a randomized cross-over study.
Study population:
Thirteen healthy overweight/obese males and postmenopausal females, aged between 45-75 years and BMI between 27-38 kg/m2, with liver fat content ≥ 5% will participate in the study. To be able to include enough people with a liver fat content ≥5%, around 27 participants are expected to be screened for liver fat. When liver fat content is <5%, participants will not be included in the study after determination of liver fat content.
Main study parameters/endpoints:
The primary study outcome is hepatic fat oxidation measured as plasma beta-hydroxybutyrate (BHB) levels, which will be measured before and after one night adherence to the fasting protocols. The secondary study outcome is DNL as determined by stable isotope techniques and will also be measured after one night adherence to the fasting protocols. Other study outcomes include hepatic glycogen content, substrate oxidation and plasma metabolites related to energy metabolism (measured before and after one night adherence to the fasting protocols) and intrahepatic fat content and composition (measured after 6 days of adherence to the fasting protocols).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Short overnight fast | Experimental | Behavioral: Overnight fasting durationOvernight fasting duration intervention: Participants will receive their last evening meal at 11 pm and stay overnight fasted afterwards for (9.5h). |
| Long overnight fast | Experimental | Behavioral: Overnight fasting durationOvernight fasting duration intervention: Participants will receive their last evening meal at 4.30 pm and stay overnight fasted afterwards for (16h). |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Signed informed consent
- Caucasian (people will be excluded when having a ≥50% racial African/Asian background)
- Male or postmenopausal female
- Aged 45-75 years at start of the study
- Body mass index (BMI) 27 - 38 kg/m2
Key exclusion criteria (6 listed)
- Type 2 diabetes
- Active diseases (cardiovascular, diabetes, liver, kidney, cancer or other)
- Contra-indication for MRI (which can be found in appendix II)
- Alcohol consumption of >2 servings per day
- Regular smoking (>5 cigarettes per day)
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 |
|---|---|---|
| Overnight fasting durationSubjects will adhere to overnight fasting protocol for 6 days | Behavioural | Long overnight fast, Short overnight fast |
Primary outcome
Hepatic fat oxidation
Time frame: 5 hours
measured as plasma BHB levels
1 secondary outcome
De novo lipogenesis (DNL)
Time frame: 20 hours
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 5 Oct 2020.
- 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.
Vera Schrauwen-Hinderling, Dr 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 Overnight fasting duration in people with Fatty Liver, Nonalcoholic and Meal Time, 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 8 inclusion and 6 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 5 Oct 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. 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?
Hepatic fat oxidation (time frame: 5 hours). 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 Oct 2020; AzTrials last refreshed its copy on 30 Oct 2026.