Non-Alcoholic Fatty Liver DiseaseNCT04004403
Alternate Day Fasting, Exercise, and NAFLD
A study testing Alternate day fasting and Exercise in people with Non-Alcoholic Fatty Liver Disease and Obesity, run by University of Illinois at Chicago at 1 site in United States.
Trial summary
Approximately 65% of obese individuals have non-alcoholic fatty liver disease (NAFLD), and this condition is strongly related to the development of insulin resistance and diabetes. Innovative lifestyle strategies to treat NAFLD are critically needed. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Obesity
- What is being tested?
- Alternate day fasting and Exercise
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2019to 1 May 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age between 18 to 65 years old
- BMI between 30.0 and 59.9 kg/m2
- NAFLD (hepatic steatosis ≥ 5% confirmed by MRI-PDFF)
- Sedentary (<20 min, 2x/week of light activity at 3-4 metabolic equivalents (METs) for 3 mo prior to study)
Who cannot join
- Have chronic liver disease other than NAFLD (hepatitis B or C, primary biliary cirrhosis, sclerosing cholangitis, autoimmune hepatitis, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency)
- Consume excessive amounts of alcohol women: 70 g of ethanol (5 alcoholic drinks per week) and men 140 g of ethanol (10 drinks per week) in the past 6 months)
- Have a history of known cardiovascular, pulmonary or renal disease
- Diagnosed T1DM or T2DM
- Are not weight stable for 3 months prior to the beginning of study (weight gain or loss > 4 kg)
- Are claustrophobic or have implanted metallic/electrical devices (e.g. cardiac pacemaker, neuro-stimulator)
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- Are taking drugs that induce steatosis (e.g. corticosteroids, estrogens, methotrexate, Ca channel blockers)
- Are taking drugs that benefit NAFLD (e.g. betaine, pioglitazone, rosiglitazone, metformin, or gemifibrozil)
- Are taking drugs that influence study outcomes (weight loss medications)
- Are perimenopausal or have an irregular menstrual cycle (menses that does not appear every 27-32 days)
- Are pregnant, or trying to become pregnant
- Are smokers
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Illinois Chicago
Chicago, Illinois, 60612
About this study
Official title: Alternate Day Fasting Combined With Exercise for the Treatment of Non-alcoholic Fatty Liver Disease (NAFLD)
Approximately 65% of obese individuals have non-alcoholic fatty liver disease (NAFLD), and this condition is strongly related to the development of insulin resistance and diabetes. Innovative lifestyle strategies to treat NAFLD are critically needed. The proposed research will demonstrate that alternate day fasting (ADF) combined with exercise is an effective non-pharmacological therapy to treat NAFLD.
Read the detailed description
Nonalcoholic fatty liver disease (NAFLD) is characterized by an accumulation of fat in the liver (not resulting from excessive alcohol consumption). Approximately 65% of obese individuals have NAFLD, and this condition is strongly related to the development of insulin resistance and type 2 diabetes. While certain pharmacological agents have been shown to reduce liver fat (i.e. thiazolidinediones), there is mounting concern regarding the safety and weight-gaining effects of these compounds. In light of this, recent research has focused on non-pharmacological lifestyle therapies to reduce hepatic steatosis, such as daily calorie restriction combined with aerobic exercise. Evidence from clinical trials suggest that this combination is an effective lifestyle therapy improve liver fat content and hepatic insulin sensitivity.
More recently, it's been shown that intermittent fasting may produce even greater improvements in hepatic steatosis and hepatic insulin sensitivity, when compared to conventional calorie restriction. For instance, intrahepatic lipid accumulation was lower and insulin sensitivity was higher in mice fasted every other day, when compared to mice who were energy restricted every day. Moreover, data from human trials show that adults with obesity experience greater decreases in insulin and insulin resistance with intermittent fasting versus daily restriction. These findings suggest that intermittent fasting may be a more effective diet therapy to reduce hepatic steatosis and improve insulin sensitivity, when compared to daily calorie restriction. Although these findings are very promising, these data still require confirmation by a randomized controlled clinical trial.
- Conditions
- Non-Alcoholic Fatty Liver Disease, Obesity
- Being tested
- Alternate day fasting, Exercise
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alternate day fastingOther
The diet involves consuming 600 kcal on the "fast day" and eat ad libitum at home on alternating "feed days".
ExerciseOther
The exercise intervention involves supervised aerobic exercise program 5 times per week, 40-60 min per session, 60-85% HRmax.
| Study group | Role | What they receive |
|---|---|---|
| Alternate day fasting | Experimental | These participants will consume 600 kcal on the "fast day" and eat ad libitum at home on alternating "feed days". Receives: Other: Alternate day fasting |
| Exercise | Experimental | These participants will participate in a supervised aerobic exercise program 5 times per week, 40-60 min per session, 60-85% HRmax. Receives: Other: Exercise |
| Combination alternate day fasting plus exercise | Experimental | These participants will consume 600 kcal on the "fast day" and eat ad libitum at home on alternating "feed days". They will also participate in a supervised aerobic exercise program 5 times per week, 40-60 min per session, 60-85% HRmax. Receives: Other: Alternate day fasting; Other: Exercise |
| Control | No intervention | Controls will be instructed to maintain their weight throughout the trial, and not to change eating or physical activity habits. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Hepatic Steatosis
Hepatic steatosis will be measured by magnetic resonance imaging (MRI-PDFF)
Measured: Change from week 1 to week 12
Secondary outcomes (7)
Change in Body Weight
Measured by digital scale
Measured: Change from week 1 to week 12
Change in Alanine Aminotransferase (ALT)
Measured by a commercial lab (Medstar, Inc)
Measured: Change from week 1 to week 12
Change in Aspartate Aminotransferase (AST)
Measured by a commercial lab (Medstar, Inc)
Measured: Change from week 1 to week 12
Change in Fasting Glucose
Measured by a commercial lab (Medstar, Inc)
Measured: Change from week 1 to week 12
Change in Fasting Insulin
Measured by a commercial lab (Medstar, Inc)
Measured: Change from week 1 to week 12
Change in Insulin Resistance
Measured by Homeostatic model assessment of insulin resistance (HOMA-IR). The HOMA-IR value was calculated using the formula: [HOMA-IR = glucose (mg/dL) × insulin (mU/L)/405]. Interpretation of HOMA-IR Scores: < 1.0: Normal insulin sensitivity; 1.0-1.9: Mild insulin resistance; > 2.0: Moderate to severe insulin resistance.
Measured: Change from week 1 to week 12
Change in HbA1c
Measured by a commercial lab (Medstar, Inc)
Measured: Change from week 1 to week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2019
- Study start1 Sep 2019
- Primary completion1 May 2024
- Study completion1 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Illinois at Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Krista Varady, University of Illinois at Chicago
- Investigators
- Krista Varady, PhD, Principal investigator, University of Illinois at Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04004403
- Sponsor's protocol ID
- 2019-0300
- Other IDs
- R01DK119783
- Status last verified
- Sep 2025
- First submitted
- 28 Jun 2019
- Last updated
- 25 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will not be shared.
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alternate Day Fasting Combined With Exercise for the Treatment of Non-alcoholic Fatty Liver Disease (NAFLD)
- ClinicalTrials.gov ID
- NCT04004403
- Acronym / sponsor ID
- 2019-0300
- Conditions
- Non-Alcoholic Fatty Liver Disease, Obesity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- University of Illinois at ChicagoUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 1 May 2024 (actual)
- Study completion
- 1 May 2024 (actual)
- First posted
- 2 Jul 2019 (actual)
- Results
- Posted 25 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Approximately 65% of obese individuals have non-alcoholic fatty liver disease (NAFLD), and this condition is strongly related to the development of insulin resistance and diabetes. Innovative lifestyle strategies to treat NAFLD are critically needed. The proposed research will demonstrate that alternate day fasting (ADF) combined with exercise is an effective non-pharmacological therapy to treat NAFLD.
Detailed description
Nonalcoholic fatty liver disease (NAFLD) is characterized by an accumulation of fat in the liver (not resulting from excessive alcohol consumption). Approximately 65% of obese individuals have NAFLD, and this condition is strongly related to the development of insulin resistance and type 2 diabetes. While certain pharmacological agents have been shown to reduce liver fat (i.e. thiazolidinediones), there is mounting concern regarding the safety and weight-gaining effects of these compounds. In light of this, recent research has focused on non-pharmacological lifestyle therapies to reduce hepatic steatosis, such as daily calorie restriction combined with aerobic exercise. Evidence from clinical trials suggest that this combination is an effective lifestyle therapy improve liver fat content and hepatic insulin sensitivity.
More recently, it's been shown that intermittent fasting may produce even greater improvements in hepatic steatosis and hepatic insulin sensitivity, when compared to conventional calorie restriction. For instance, intrahepatic lipid accumulation was lower and insulin sensitivity was higher in mice fasted every other day, when compared to mice who were energy restricted every day. Moreover, data from human trials show that adults with obesity experience greater decreases in insulin and insulin resistance with intermittent fasting versus daily restriction. These findings suggest that intermittent fasting may be a more effective diet therapy to reduce hepatic steatosis and improve insulin sensitivity, when compared to daily calorie restriction. Although these findings are very promising, these data still require confirmation by a randomized controlled clinical trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Alternate day fasting | Experimental | Other: Alternate day fastingThese participants will consume 600 kcal on the "fast day" and eat ad libitum at home on alternating "feed days". |
| Exercise | Experimental | Other: ExerciseThese participants will participate in a supervised aerobic exercise program 5 times per week, 40-60 min per session, 60-85% HRmax. |
| Combination alternate day fasting plus exercise | Experimental | Other: Alternate day fasting, Other: ExerciseThese participants will consume 600 kcal on the "fast day" and eat ad libitum at home on alternating "feed days". They will also participate in a supervised aerobic exercise program 5 times per week, 40-60 min per session, 60-85% HRmax. |
| Control | No intervention | –Controls will be instructed to maintain their weight throughout the trial, and not to change eating or physical activity habits. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age between 18 to 65 years old
- BMI between 30.0 and 59.9 kg/m2
- NAFLD (hepatic steatosis ≥ 5% confirmed by MRI-PDFF)
- Sedentary (<20 min, 2x/week of light activity at 3-4 metabolic equivalents (METs) for 3 mo prior to study)
Key exclusion criteria (12 listed)
- Have chronic liver disease other than NAFLD (hepatitis B or C, primary biliary cirrhosis, sclerosing cholangitis, autoimmune hepatitis, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency)
- Consume excessive amounts of alcohol women: 70 g of ethanol (5 alcoholic drinks per week) and men 140 g of ethanol (10 drinks per week) in the past 6 months)
- Have a history of known cardiovascular, pulmonary or renal disease
- Diagnosed T1DM or T2DM
- Are not weight stable for 3 months prior to the beginning of study (weight gain or loss > 4 kg)
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 |
|---|---|---|
| Alternate day fastingThe diet involves consuming 600 kcal on the "fast day" and eat ad libitum at home on alternating "feed days". | Other | Alternate day fasting, Combination alternate day fasting plus exercise |
| ExerciseThe exercise intervention involves supervised aerobic exercise program 5 times per week, 40-60 min per session, 60-85% HRmax. | Other | Combination alternate day fasting plus exercise, Exercise |
Primary outcome
Change in Hepatic Steatosis
Time frame: Change from week 1 to week 12
Hepatic steatosis will be measured by magnetic resonance imaging (MRI-PDFF)
7 secondary outcomes
Change in Body Weight
Time frame: Change from week 1 to week 12
Change in Alanine Aminotransferase (ALT)
Time frame: Change from week 1 to week 12
Change in Aspartate Aminotransferase (AST)
Time frame: Change from week 1 to week 12
Change in Fasting Glucose
Time frame: Change from week 1 to week 12
Change in Fasting Insulin
Time frame: Change from week 1 to week 12
Change in Insulin Resistance
Time frame: Change from week 1 to week 12
Change in HbA1c
Time frame: Change from week 1 to week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. IPD will not be shared.
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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.
Krista Varady, PhD principal investigator
University of Illinois at Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Alternate day fasting and Exercise in people with Non-Alcoholic Fatty Liver Disease and Obesity, run by University of Illinois at Chicago at 1 site in United States.
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 12 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 25 Sep 2025. 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 United States. 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?
Yes. Results are posted in the registry (first posted 25 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Hepatic Steatosis (time frame: Change from week 1 to week 12). 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 25 Sep 2025; AzTrials last refreshed its copy on 29 Oct 2026.