Non-Alcoholic Fatty Liver DiseaseNCT05968378
Diet, Immunometabolism and Non-alcoholic Fatty Liver Disease
A study testing Standard healthy eating advice and eTRE plus Mediterranean diet in people with Non-Alcoholic Fatty Liver Disease and Liver Fat, run by University College Dublin at 1 site in Ireland.
Trial summary
This study will assess the impact of 8-hour time restricted eating (8 hours of eating, 16 hours fasting) combined with a Mediterranean diet on metabolism and inflammation in adults with non-alcoholic fatty liver disease (NAFLD). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Liver Fat, Obesity
- What is being tested?
- Standard healthy eating advice and eTRE plus Mediterranean diet
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteIreland
- Study dates
- 1 Jun 2023to Jul 2024
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females
- Age 18-65 years, from all ethnic groups, capable of providing informed consent to participate
- Obesity (body mass index >30kg/m^2) and of stable body weight (±3% for ≥3 months)
- Fasting blood glucose <7.0 mmol/L and HbA1c <6.5%.
- Liver fat >10% (CAP score >238 dB/m) and no fibrosis (liver stiffness score 2-7 kPa) as assessed by liver elastography (FibroScan)
Who cannot join
- Impaired renal function
- Abnormal hematocrit
- History of cardiovascular events
- Uncontrolled hypertension
- Type 2 diabetes
- Medications or supplements known to affect glucose or lipid metabolism
Show all 10Show fewer
- Active inflammatory, autoimmune, infectious, gastrointestinal, or malignant disease
- Uncontrolled neurological or psychiatric disease
- Iron deficiency anemia, (hemoglobin < 12g/dl men, < 11g/dl women)
- Fatty acid supplements and consumers of high doses of anti- antioxidant vitamins (A, C, E, b-carotene)
Trial locations and contacts
1 site in 1 country.
Christopher E Shannon, PhD contact
Ireland1 site, 1 recruiting
- Recruiting
University College Dublin
Dublin, Leinster, D04 V1W8
Helen M Roche, Professor, +353 01 7164031, helen.roche@ucd.ie
Christopher E Shannon, PhD, christopher.shannon@ucd.ie
About this study
Official title: Immunometabolic Effects of Time Restricted Eating in Non-alcoholic Fatty Liver Disease
This study will assess the impact of 8-hour time restricted eating (8 hours of eating, 16 hours fasting) combined with a Mediterranean diet on metabolism and inflammation in adults with non-alcoholic fatty liver disease (NAFLD).
Read the detailed description
Non-alcoholic fatty liver disease (NAFLD), defined as the accumulation of fat in the liver that is not related to alcohol intake, is the number 1 global cause of chronic liver disease. Excessive consumption of energy, saturated fat, and simple sugars is a key contributor to hepatic lipid accumulation and obesity-induced metabolic inflammation, reflecting cross-talk between immune and metabolic pathways. Moreover, dietary factors including saturated fatty acids, cholesterol, and their derivatives, as well as gut-derived metabolites, can prime innate immune cells to induce an exaggerated pro-inflammatory response upon re-exposure to such stimuli and may contribute to chronic low grade inflammation.
Dietary strategies focusing on replacing inflammatory dietary triggers with monounsaturated fats, fiber and complex carbohydrates have been shown to improve metabolic dysfunction, but how this relates to a rewiring of the innate immune system is less clear. Time-restricted eating (TRE) is another dietary strategy which has been shown to elicit beneficial effects that reduce the risk of chronic metabolic disease and consolidates eating to a 6-10 hour period daily. Early TRE (eTRE), wherein eating occurs from morning to early afternoon, is associated with greater cardiometabolic health benefits than eating late in the evening. This includes improved insulin sensitivity, glucose tolerance and lipid metabolism, and reduced inflammatory markers.
This study will determine the impact of an 8-week intervention of 8-hour eTRE combined with an anti-inflammatory Mediterranean diet on the metabolic and immune phenotype of individuals with NAFLD, a population at high risk of progressive cardiometabolic decline and chronic inflammation. By focusing on improving both nutrient quality and nutrient timing, a greater understanding of the interaction between systemic metabolism and immune cell rewiring will be gained.
- Conditions
- Non-Alcoholic Fatty Liver Disease, Liver Fat, Obesity, Inflammation
- Being tested
- Standard healthy eating advice, eTRE plus Mediterranean diet
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Fatty Liver, Obesity, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard healthy eating adviceBehavioural
Subjects in this group will be provided with standard healthy eating advice according to the Irish National Healthy Eating Guidelines and Food Pyramid and will be asked to follow this advice for 8-weeks.
eTRE plus Mediterranean dietBehavioural
Subjects in this group will be asked to consume all meals between 8am - 4pm and to adhere to a Mediterranean style diet daily for 8-weeks.
| Study group | Role | What they receive |
|---|---|---|
| Standard healthy eating advice | Active comparator | Subjects in this group will be counselled according to the Irish National Healthy Eating Guidelines. Receives: Behavioral: Standard healthy eating advice |
| eTRE plus Mediterranean diet | Experimental | Subjects in this group will be asked to restrict their eating to 8-hours daily (8am - 4pm) and to adhere to a Mediterranean style diet. Receives: Behavioral: eTRE plus Mediterranean diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in plasma inflammatory response to a high-fat meal: C-reactive protein (CRP)
Postprandial changes in CRP (mg/L) will be measured in response to a high-fat meal
Measured: To be assessed at baseline and post 8-week intervention
Change in plasma inflammatory response to a high-fat meal: Interleukin-6 (IL-6)
Postprandial changes in IL-6 (pg/mL) will be measured in response to a high-fat meal
Measured: To be assessed at baseline and post 8-week intervention
Change in plasma inflammatory response to a high-fat meal: Interleukin-1-beta (IL-1β)
Postprandial changes in IL-1β (pg/mL) will be measured in response to a high-fat meal
Measured: To be assessed at baseline and post 8-week intervention
Change in plasma inflammatory response to a high-fat meal: Tumor necrosis factor alpha (TNF-α)
Postprandial changes in (TNF-α) (pg/mL) will be measured in response to a high-fat meal
Measured: To be assessed at baseline and post 8-week intervention
Secondary outcomes (20)
Change in metabolic response to a high-fat meal: Glucose
Plasma glucose (mg/dL) response to a high-fat meal will be assessed
Measured: To be assessed at baseline and post 8-week intervention
Change in metabolic response to a high-fat meal: Insulin
Plasma insulin (μU/mL) response to a high-fat meal will be assessed
Measured: To be assessed at baseline and post 8-week intervention
Change in metabolic response to a high-fat meal: Glucagon
Plasma glucagon (pg/mL) response to a high-fat meal will be assessed
Measured: To be assessed at baseline and post 8-week intervention
Change in metabolic response to a high-fat meal: Triglycerides
Plasma triglycerides (mg/dL) response to a high-fat meal will be assessed
Measured: To be assessed at baseline and post 8-week intervention
Change in metabolic response to a high-fat meal: Non-esterified fatty acids (NEFA)
Plasma NEFA (mmol/L) response to a high-fat meal will be assessed
Measured: To be assessed at baseline and post 8-week intervention
Innate immune function
8-week change in innate immune function will be assessed ex-vivo using whole blood simulation assay.
Measured: To be assessed at baseline and post 8-week intervention
Innate immune training
8-week change in innate immune function will be assessed in isolated monocytes stimulated with beta glucan and restimulated with lipopolysaccharide.
Measured: To be assessed at baseline and post 8-week intervention
Insulin resistance
8-week change in insulin resistance using Homeostatic Model Assessment for Insulin Resistance (HOMA-IR).
Measured: To be assessed at baseline and post 8-week intervention
Adipose tissue insulin resistance
8-week change in adipose tissue insulin resistance using the adipose tissue insulin resistance index (Adipo-IR).
Measured: To be assessed at baseline and post 8-week intervention
Change in intrahepatic triglyceride content
Liver elastography (FibroScan) will be used to determine change in liver fat after the 8-week intervention.
Measured: To be assessed at baseline and post 8-week intervention
Change in liver stiffness measurement
Liver elastography (FibroScan) will be used to determine change in liver stiffness after the 8-week intervention.
Measured: To be assessed at baseline and post 8-week intervention
HDL Proteome
8-week change in the composition of the HDL proteome.
Measured: To be assessed at baseline and post 8-week intervention
Body weight
8-week change in body weight in kilograms
Measured: To be assessed at baseline and post 8-week intervention
Body mass index (BMI)
8-week change in BMI
Measured: To be assessed at baseline and post 8-week intervention
Body fat percentage
8 week change in body fat percentage using bioelectrical impedance analysis
Measured: To be assessed at baseline and post 8-week intervention
Waist and hip circumferences
8-week change in waist and hip circumference measured in centimeters using a body tape measure
Measured: To be assessed at baseline and post 8-week intervention
Gut microbiome composition and function
8-week functional changes in gut microbiome will be assessed by integrating 16S sequencing of fecal samples with fecal water metabolomics.
Measured: To be assessed at baseline and post 8-week intervention
Dietary intake
8-week change in dietary intake using a 3-day semi-weighed food diary.
Measured: To be assessed at baseline and post 8-week intervention
Physical activity level (PAL)
8-week change in PAL using the International Physical Activity Questionnaire - Short form (IPAQ-SF). This form has 7 questions about time spent doing physical activity(leisure time, work, domestic tasks, and travel) in the last 7 days. Activities are grouped according to vigorous or moderate intensity, and walking. Each intensity is assigned a metabolic equivalent (MET). The time spent at each intensity is used to estimate weekly physical activity using the associated METs. Minimum and maximum values are 0 and 154,224 METs. Classification as 'sufficiently active' requires ≥600 METs/week which may be achieved through a combination of intensities. Classification as 'highly active' requires: a) vigorous-intensity activity on ≥3 days achieving a minimum of ≥1500 METs/week OR b) ≥7 days of any combination of walking, moderate-intensity or vigorous-intensity activities achieving ≥ 3000 METs/week. A physical activity level below these categories is undesirable.
Measured: To be assessed at baseline and post 8-week intervention
Mediterranean diet adherence
8-week change in Mediterranean diet adherence score using the PREDIMED 14-item Mediterranean Diet Assessment Tool. This questionnaire is used to assess adherence to the traditional Mediterranean Diet. Two of the 14 questions relate to the use of olive oil, a key component of the Mediterranean Diet, and 12 questions relate to the consumption of foods which characterize the Mediterranean Diet. Each item has a criteria which must be met to achieve 1 point e.g., at least 3 pieces of fruit daily. The minimum score is 0 and the maximum is 14, where a score of ≤ 5 indicates low adherence, 6-9 moderate adherence, and > 9 high adherence.
Measured: To be assessed at baseline and post 8-week intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2023
- Study start1 Jun 2023
- Primary completionJun 2024 (estimated)
- Study completionJul 2024 (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.
- 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
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College Dublin
- Sponsor type
- University, hospital or other
- Collaborators
- St. James's Hospital, Ireland
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05968378
- Sponsor's protocol ID
- LS-E-22-105-Shannon-Roche
- Status last verified
- Jul 2023
- First submitted
- 26 Jun 2023
- Last updated
- 1 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunometabolic Effects of Time Restricted Eating in Non-alcoholic Fatty Liver Disease
- ClinicalTrials.gov ID
- NCT05968378
- Acronym / sponsor ID
- LS-E-22-105-Shannon-Roche
- Conditions
- Non-Alcoholic Fatty Liver Disease, Liver Fat, Obesity, Inflammation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University College DublinUniversity, hospital or other
- Collaborators
- St. James's Hospital, Ireland
- Study start
- 1 Jun 2023 (actual)
- Primary completion
- Jun 2024 (estimated)
- Study completion
- Jul 2024 (estimated)
- First posted
- 1 Aug 2023 (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.
This study will assess the impact of 8-hour time restricted eating (8 hours of eating, 16 hours fasting) combined with a Mediterranean diet on metabolism and inflammation in adults with non-alcoholic fatty liver disease (NAFLD).
Detailed description
Non-alcoholic fatty liver disease (NAFLD), defined as the accumulation of fat in the liver that is not related to alcohol intake, is the number 1 global cause of chronic liver disease. Excessive consumption of energy, saturated fat, and simple sugars is a key contributor to hepatic lipid accumulation and obesity-induced metabolic inflammation, reflecting cross-talk between immune and metabolic pathways. Moreover, dietary factors including saturated fatty acids, cholesterol, and their derivatives, as well as gut-derived metabolites, can prime innate immune cells to induce an exaggerated pro-inflammatory response upon re-exposure to such stimuli and may contribute to chronic low grade inflammation.
Dietary strategies focusing on replacing inflammatory dietary triggers with monounsaturated fats, fiber and complex carbohydrates have been shown to improve metabolic dysfunction, but how this relates to a rewiring of the innate immune system is less clear. Time-restricted eating (TRE) is another dietary strategy which has been shown to elicit beneficial effects that reduce the risk of chronic metabolic disease and consolidates eating to a 6-10 hour period daily. Early TRE (eTRE), wherein eating occurs from morning to early afternoon, is associated with greater cardiometabolic health benefits than eating late in the evening. This includes improved insulin sensitivity, glucose tolerance and lipid metabolism, and reduced inflammatory markers.
This study will determine the impact of an 8-week intervention of 8-hour eTRE combined with an anti-inflammatory Mediterranean diet on the metabolic and immune phenotype of individuals with NAFLD, a population at high risk of progressive cardiometabolic decline and chronic inflammation. By focusing on improving both nutrient quality and nutrient timing, a greater understanding of the interaction between systemic metabolism and immune cell rewiring will be gained.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard healthy eating advice | Active comparator | Behavioral: Standard healthy eating adviceSubjects in this group will be counselled according to the Irish National Healthy Eating Guidelines. |
| eTRE plus Mediterranean diet | Experimental | Behavioral: eTRE plus Mediterranean dietSubjects in this group will be asked to restrict their eating to 8-hours daily (8am - 4pm) and to adhere to a Mediterranean style diet. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Males and females
- Age 18-65 years, from all ethnic groups, capable of providing informed consent to participate
- Obesity (body mass index >30kg/m^2) and of stable body weight (±3% for ≥3 months)
- Fasting blood glucose <7.0 mmol/L and HbA1c <6.5%.
- Liver fat >10% (CAP score >238 dB/m) and no fibrosis (liver stiffness score 2-7 kPa) as assessed by liver elastography (FibroScan)
Key exclusion criteria (10 listed)
- Impaired renal function
- Abnormal hematocrit
- History of cardiovascular events
- Uncontrolled hypertension
- Type 2 diabetes
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 |
|---|---|---|
| Standard healthy eating adviceSubjects in this group will be provided with standard healthy eating advice according to the Irish National Healthy Eating Guidelines and Food Pyramid and will be asked to follow this advice for 8-weeks. | Behavioural | Standard healthy eating advice |
| eTRE plus Mediterranean dietSubjects in this group will be asked to consume all meals between 8am - 4pm and to adhere to a Mediterranean style diet daily for 8-weeks. | Behavioural | eTRE plus Mediterranean diet |
Primary outcome
Change in plasma inflammatory response to a high-fat meal: C-reactive protein (CRP)
Time frame: To be assessed at baseline and post 8-week intervention
Postprandial changes in CRP (mg/L) will be measured in response to a high-fat meal
Change in plasma inflammatory response to a high-fat meal: Interleukin-6 (IL-6)
Time frame: To be assessed at baseline and post 8-week intervention
Postprandial changes in IL-6 (pg/mL) will be measured in response to a high-fat meal
Change in plasma inflammatory response to a high-fat meal: Interleukin-1-beta (IL-1β)
Time frame: To be assessed at baseline and post 8-week intervention
Postprandial changes in IL-1β (pg/mL) will be measured in response to a high-fat meal
Change in plasma inflammatory response to a high-fat meal: Tumor necrosis factor alpha (TNF-α)
Time frame: To be assessed at baseline and post 8-week intervention
Postprandial changes in (TNF-α) (pg/mL) will be measured in response to a high-fat meal
20 secondary outcomes
Change in metabolic response to a high-fat meal: Glucose
Time frame: To be assessed at baseline and post 8-week intervention
Change in metabolic response to a high-fat meal: Insulin
Time frame: To be assessed at baseline and post 8-week intervention
Change in metabolic response to a high-fat meal: Glucagon
Time frame: To be assessed at baseline and post 8-week intervention
Change in metabolic response to a high-fat meal: Triglycerides
Time frame: To be assessed at baseline and post 8-week intervention
Change in metabolic response to a high-fat meal: Non-esterified fatty acids (NEFA)
Time frame: To be assessed at baseline and post 8-week intervention
Innate immune function
Time frame: To be assessed at baseline and post 8-week intervention
Innate immune training
Time frame: To be assessed at baseline and post 8-week intervention
Insulin resistance
Time frame: To be assessed at baseline and post 8-week intervention
Adipose tissue insulin resistance
Time frame: To be assessed at baseline and post 8-week intervention
Change in intrahepatic triglyceride content
Time frame: To be assessed at baseline and post 8-week intervention
Change in liver stiffness measurement
Time frame: To be assessed at baseline and post 8-week intervention
HDL Proteome
Time frame: To be assessed at baseline and post 8-week intervention
Body weight
Time frame: To be assessed at baseline and post 8-week intervention
Body mass index (BMI)
Time frame: To be assessed at baseline and post 8-week intervention
Body fat percentage
Time frame: To be assessed at baseline and post 8-week intervention
Waist and hip circumferences
Time frame: To be assessed at baseline and post 8-week intervention
Gut microbiome composition and function
Time frame: To be assessed at baseline and post 8-week intervention
Dietary intake
Time frame: To be assessed at baseline and post 8-week intervention
Physical activity level (PAL)
Time frame: To be assessed at baseline and post 8-week intervention
Mediterranean diet adherence
Time frame: To be assessed at baseline and post 8-week intervention
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2023.
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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.
Christopher E Shannon, PhD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Standard healthy eating advice and eTRE plus Mediterranean diet in people with Non-Alcoholic Fatty Liver Disease and Liver Fat, run by University College Dublin at 1 site in Ireland.
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 5 inclusion and 10 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 1 Aug 2023. 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 Ireland. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Helen M Roche, Professor (+353017164031, helen.roche@ucd.ie), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in plasma inflammatory response to a high-fat meal: C-reactive protein (CRP) (time frame: To be assessed at baseline and post 8-week intervention). The study lists 4 primary outcomes in all. 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 1 Aug 2023.