Non-Alcoholic Fatty Liver DiseaseDAIPRO-NAFLDNCT04841915
Dairy Protien Rich Diet for NAFLD Patients
A study testing High-Protein Diet, Clinical dietician and Weight loss in people with Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome, run by University of Aarhus at 2 sites in Denmark.
Trial summary
The overarching aim of this project is to investigate effects of dietary interventions on nonalcoholic fatty liver disease (NAFLD) severity and to delineate the relationship with improvements in metabolic aberrations in liver-, fat- and muscle tissue, using a panel of state-of-the art techniques. Read more about this study
- Who is it for?
- Ages 25 to 70 years
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Metabolic Syndrome, Caseins
- What is being tested?
- High-Protein Diet, Clinical dietician and Weight loss
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 2 sitesDenmark
- Study dates
- 15 Mar 2021to 1 Dec 2023
- 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 25 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- BMI ≥ 27.5 kg/m2
- HbA1C < 48 mmol/mol
- Written informed consent
- Liver steatosis > 10% on MR-spectroscopy
- Premenopausal women will have a negative pregnancy test drawn within 48 hours before the study.
Who cannot join
- Other chronic liver diseases (HBV, HCV, AIH, PBC, PSC, alcoholic steatosis)
- Known systemic disease exempting hypertension and dyslipidemia.
- Former or active malignant disease
- Alcohol consumption >2 drinks/day for men, 1 drink/day for women, evaluated by AUDIT-C
- Pregnancy
- Any medications including non-prescription medications exempting, birth control medications, antihypertensives and statins. Participants taking statins can participate on the condition of a 2 week pause before the experimental days.
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- Estimated glomerular filtration rate <90 ml/min
- Currently smoking
- Blood donation within the last 3 months
- Weight above 130 kg
- Participated in trials using radioactive isotopes within the last 6 months
Trial locations and contacts
2 sites in 1 country.
Denmark2 sites
Aarhus University Hospital, Dept. Hepatology and Gastroenterology
Aarhus N, 8200
Hvidovre Hospital
Hvidovre, 2650
About this study
Official title: A Randomized Controlled Trial of Effects of DAIry PROtein Products on Liver Disease Severity and Metabolism in Patients With Non-Alcoholic Fatty Liver Disease.
The overarching aim of this project is to investigate effects of dietary interventions on nonalcoholic fatty liver disease (NAFLD) severity and to delineate the relationship with improvements in metabolic aberrations in liver-, fat- and muscle tissue, using a panel of state-of-the art techniques.
The investigators will conduct a randomized clinical trial with three arms to investigate if micellar cassein isolate and whey protein supplementation as part of a high-protein diet during 4 weeks of weight maintenance and 20 weeks of hypocaloric intake (30% energy restriction) inducing modest weight loss (5% of baseline weight) has beneficial effects on NAFLD severity and metabolic aberrations compared to normal diet in NAFLD patients.
It is hypothesized that: (i) a high-protein diet improves liver disease severity and metabolic function compared to a normal protein diet; (ii) Cassein provides greater benefits than whey; and(iii) these effects manifest during both weight maintenance and weight loss.
Read the detailed description
To test the hypothesis, state-of-the-art techniques for a comprehensive assessment of liver disease severity and metabolic function will be employed. NAFLD severity and treatment effects will be evaluated on the basis of liver fat content (MR spectroscopy), liver enzymes, liver-specific inflammation and fibrosis markers and fibrosis (fibroscan). Metabolic function will be investigated by basal and insulin mediated whole-body glucose, fatty acid and VLDL-TG turnover, postprandial insulin secretion and clearance (mixed meal test in conjunction with oral minimal modeling). Body composition (total fat mass, leg fat and fat free mass) will be assessed by DEXA-scanning; visceral and upper-body subcutaneous fat by MR-imaging, and fat content of skeletal muscle and liver by MR-spectroscopy. All outcomes will be assessed at baseline, after 4 wk on a eucaloric diet (weight maintenance), and after an additional 20 wk on a hypocaloric diet (5% weight loss), in 54 patients with NAFLD and obesity (BMI ≥30 kg/m2) but without diabetes. Subjects will be block randomized to one of three treatment groups (WPI, MCI, or standard diet, n=18 in each group). A biobank of serum/plasma/DNA including fat and skeletal muscle biopsies will be established for mechanistic analysis in a planned future work-package. Patient related outcomes will include specific questionnaires (CLDQ-NAFLD, SF-36).
All subjects will be phone-contacted on a regular basis by study personnel to monitor progress, resolve problems with the diets, and reinforce compliance; and meet in person with the study dietitians weekly during the weight maintenance phase and biweekly during the weight loss phase to have their body weight measured and receive dietary counselling. Before study initiation, the research teams will put together standardized procedures for patient contact and nutrition counselling, including creating nutrition information leaflets specific to each randomization arm, to ensure uniformity between the study centers. In practice, dietary guidance will be tailored to the individual patient to ensure weight maintenance within 2% of baseline body weight during the first phase (weight stability), and a weight loss of 0.25% per week to reach the target 5% weight loss after 20 weeks during the second phase (weight loss); energy intake will be adjusted as necessary by adding or removing carbohydrate to meet the desired goals. Three-day diet records will be collected before and every 2 weeks during the interventions to evaluate energy and macronutrient intakes. A 3-hour urine sample will be collected during the mixed meal test at baseline, after 4 and 24 weeks in order to monitor dietary protein intake. Participants will be instructed in how to do the sampling and storing the sample cool during the collection.
- Conditions
- Non-Alcoholic Fatty Liver Disease, Metabolic Syndrome, Caseins, Whey, Diet, High Protein, Weight Loss
- Being tested
- High-Protein Diet, Clinical dietician, Weight loss
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Metabolic Syndrome, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-Protein DietDietary supplement
Diet consisting of 25E% from assigned protein during eucaloric diet and 35E% from assigned protein during hypocaloric diet
Clinical dieticianBehavioural
Counselling from a clinical dietician bi-weekly until weight loss of 5% is achieved.
Weight lossBehavioural
4 weeks eucaloric diet ~13 MJ/day followed by, 20 weeks hypocaloric diet ~9 MJ/day until 5% weight loss is achieved.
| Study group | Role | What they receive |
|---|---|---|
| Micellar Cassein Isolate High-Protein Diet | Experimental | 4weeks eucaloric intake on high-protein diet with micellar cassein as primary protein source followed by 20weeks hypocaloric intake on equivalent protein rich diet. Receives: Dietary Supplement: High-Protein Diet; Behavioral: Clinical dietician; Behavioral: Weight loss |
| Whey Protein High-Protein Diet | Experimental | 4weeks eucaloric intake on high-protein diet with whey protein as primary protein source followed by 20weeks hypocaloric intake on equivalent protein rich diet. Receives: Dietary Supplement: High-Protein Diet; Behavioral: Clinical dietician; Behavioral: Weight loss |
| Normal Diet | Placebo comparator | 4weeks eucaloric diet with normal protein content (15E%) followed by 20weeks hypocaloric intake on equivalent diet. Receives: Behavioral: Clinical dietician; Behavioral: Weight loss |
What is being measured
The primary outcome is the main question the study is designed to answer.
Steatosis, absolute
Absolute difference in changes in steatosis (MRs) between diets
Measured: 4 weeks and 20 weeks
Steatosis, relative
Relative difference in changes in steatosis (MRs) between diets
Measured: 4 weeks and 20 weeks
Liver enzymes
Difference in change of liver enzymes between diets
Measured: 4 weeks and 20 weeks
Secondary outcomes (4)
Hepatic Insulin Resistance
Changes in hepatic insulin resistance measured by changes in suppression of EGP from basal period to clamp period.
Measured: 24 weeks
Adipose tissue Insulin Resistance
Changes in adipose insulin resistance measured by changes in suppression of lipolysis from basal period to clamp period.
Measured: 24 weeks
Peripheral insulin resistance
Changes in peripheral insulin resistance measured total rate of disappearance of glucose in hyperinsulinemic clamp.
Measured: 24 weeks
Insulin Secretion
Changes in Insulin Secretion
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2021
- Study start15 Mar 2021
- Primary completion1 Dec 2023
- Study completion1 Dec 2023
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 University of AarhusThe 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Arla Foods, University of Copenhagen, Hvidovre University Hospital
- Responsible party
- Sponsor
- Investigators
- Henning Grønbæk, Prof., Principal investigator, University of Aarhus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04841915
- Sponsor's protocol ID
- DAIPRO-NAFLD
- Acronym
- DAIPRO-NAFLD
- Status last verified
- Apr 2023
- First submitted
- 24 Mar 2021
- Last updated
- 1 Apr 2025
- 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 1 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of Effects of DAIry PROtein Products on Liver Disease Severity and Metabolism in Patients With Non-Alcoholic Fatty Liver Disease.
- ClinicalTrials.gov ID
- NCT04841915
- Acronym / sponsor ID
- DAIPRO-NAFLD / DAIPRO-NAFLD
- Conditions
- Non-Alcoholic Fatty Liver Disease, Metabolic Syndrome, Caseins, Whey, Diet, High Protein, Weight Loss
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Arla Foods, University of Copenhagen, Hvidovre University Hospital
- Study start
- 15 Mar 2021 (actual)
- Primary completion
- 1 Dec 2023 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 12 Apr 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.
The overarching aim of this project is to investigate effects of dietary interventions on nonalcoholic fatty liver disease (NAFLD) severity and to delineate the relationship with improvements in metabolic aberrations in liver-, fat- and muscle tissue, using a panel of state-of-the art techniques.
The investigators will conduct a randomized clinical trial with three arms to investigate if micellar cassein isolate and whey protein supplementation as part of a high-protein diet during 4 weeks of weight maintenance and 20 weeks of hypocaloric intake (30% energy restriction) inducing modest weight loss (5% of baseline weight) has beneficial effects on NAFLD severity and metabolic aberrations compared to normal diet in NAFLD patients.
It is hypothesized that: (i) a high-protein diet improves liver disease severity and metabolic function compared to a normal protein diet; (ii) Cassein provides greater benefits than whey; and(iii) these effects manifest during both weight maintenance and weight loss.
Detailed description
To test the hypothesis, state-of-the-art techniques for a comprehensive assessment of liver disease severity and metabolic function will be employed. NAFLD severity and treatment effects will be evaluated on the basis of liver fat content (MR spectroscopy), liver enzymes, liver-specific inflammation and fibrosis markers and fibrosis (fibroscan). Metabolic function will be investigated by basal and insulin mediated whole-body glucose, fatty acid and VLDL-TG turnover, postprandial insulin secretion and clearance (mixed meal test in conjunction with oral minimal modeling). Body composition (total fat mass, leg fat and fat free mass) will be assessed by DEXA-scanning; visceral and upper-body subcutaneous fat by MR-imaging, and fat content of skeletal muscle and liver by MR-spectroscopy. All outcomes will be assessed at baseline, after 4 wk on a eucaloric diet (weight maintenance), and after an additional 20 wk on a hypocaloric diet (5% weight loss), in 54 patients with NAFLD and obesity (BMI ≥30 kg/m2) but without diabetes. Subjects will be block randomized to one of three treatment groups (WPI, MCI, or standard diet, n=18 in each group). A biobank of serum/plasma/DNA including fat and skeletal muscle biopsies will be established for mechanistic analysis in a planned future work-package. Patient related outcomes will include specific questionnaires (CLDQ-NAFLD, SF-36).
All subjects will be phone-contacted on a regular basis by study personnel to monitor progress, resolve problems with the diets, and reinforce compliance; and meet in person with the study dietitians weekly during the weight maintenance phase and biweekly during the weight loss phase to have their body weight measured and receive dietary counselling. Before study initiation, the research teams will put together standardized procedures for patient contact and nutrition counselling, including creating nutrition information leaflets specific to each randomization arm, to ensure uniformity between the study centers. In practice, dietary guidance will be tailored to the individual patient to ensure weight maintenance within 2% of baseline body weight during the first phase (weight stability), and a weight loss of 0.25% per week to reach the target 5% weight loss after 20 weeks during the second phase (weight loss); energy intake will be adjusted as necessary by adding or removing carbohydrate to meet the desired goals. Three-day diet records will be collected before and every 2 weeks during the interventions to evaluate energy and macronutrient intakes. A 3-hour urine sample will be collected during the mixed meal test at baseline, after 4 and 24 weeks in order to monitor dietary protein intake. Participants will be instructed in how to do the sampling and storing the sample cool during the collection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Micellar Cassein Isolate High-Protein Diet | Experimental | Dietary Supplement: High-Protein Diet, Behavioral: Clinical dietician, Behavioral: Weight loss4weeks eucaloric intake on high-protein diet with micellar cassein as primary protein source followed by 20weeks hypocaloric intake on equivalent protein rich diet. |
| Whey Protein High-Protein Diet | Experimental | Dietary Supplement: High-Protein Diet, Behavioral: Clinical dietician, Behavioral: Weight loss4weeks eucaloric intake on high-protein diet with whey protein as primary protein source followed by 20weeks hypocaloric intake on equivalent protein rich diet. |
| Normal Diet | Placebo comparator | Behavioral: Clinical dietician, Behavioral: Weight loss4weeks eucaloric diet with normal protein content (15E%) followed by 20weeks hypocaloric intake on equivalent diet. |
Who may qualify
- Ages
- 25 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- BMI ≥ 27.5 kg/m2
- HbA1C < 48 mmol/mol
- Written informed consent
- Liver steatosis > 10% on MR-spectroscopy
- Premenopausal women will have a negative pregnancy test drawn within 48 hours before the study.
Key exclusion criteria (11 listed)
- Other chronic liver diseases (HBV, HCV, AIH, PBC, PSC, alcoholic steatosis)
- Known systemic disease exempting hypertension and dyslipidemia.
- Former or active malignant disease
- Alcohol consumption >2 drinks/day for men, 1 drink/day for women, evaluated by AUDIT-C
- Pregnancy
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 |
|---|---|---|
| High-Protein DietDiet consisting of 25E% from assigned protein during eucaloric diet and 35E% from assigned protein during hypocaloric diet | Dietary supplement | Micellar Cassein Isolate High-Protein Diet, Whey Protein High-Protein Diet |
| Clinical dieticianCounselling from a clinical dietician bi-weekly until weight loss of 5% is achieved. | Behavioural | Micellar Cassein Isolate High-Protein Diet, Normal Diet, Whey Protein High-Protein Diet |
| Weight loss4 weeks eucaloric diet ~13 MJ/day followed by, 20 weeks hypocaloric diet ~9 MJ/day until 5% weight loss is achieved. | Behavioural | Micellar Cassein Isolate High-Protein Diet, Normal Diet, Whey Protein High-Protein Diet |
Primary outcome
Steatosis, absolute
Time frame: 4 weeks and 20 weeks
Absolute difference in changes in steatosis (MRs) between diets
Steatosis, relative
Time frame: 4 weeks and 20 weeks
Relative difference in changes in steatosis (MRs) between diets
Liver enzymes
Time frame: 4 weeks and 20 weeks
Difference in change of liver enzymes between diets
4 secondary outcomes
Hepatic Insulin Resistance
Time frame: 24 weeks
Adipose tissue Insulin Resistance
Time frame: 24 weeks
Peripheral insulin resistance
Time frame: 24 weeks
Insulin Secretion
Time frame: 24 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 1 Apr 2025.
- 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.
Henning Grønbæk, Prof. principal investigator
University of Aarhus
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High-Protein Diet, Clinical dietician and Weight loss in people with Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome, run by University of Aarhus at 2 sites in Denmark.
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 11 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 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. 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?
Steatosis, absolute (time frame: 4 weeks and 20 weeks). The study lists 3 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 Apr 2025.