Dairy Protien Rich Diet for NAFLD Patients (DAIPRO-NAFLD)

March 26, 2025 updated by: University of Aarhus

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
46

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Denmark
      • Aarhus N, Denmark, 8200
        • Aarhus University Hospital, Dept. Hepatology and Gastroenterology
      • Hvidovre, Denmark, 2650
        • Hvidovre Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

30 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Micellar Cassein Isolate High-Protein Diet
4weeks eucaloric intake on high-protein diet with micellar cassein as primary protein source followed by 20weeks hypocaloric intake on equivalent protein rich diet.
Dietary supplement: High-Protein Diet
Diet consisting of 25E% from assigned protein during eucaloric diet and 35E% from assigned protein during hypocaloric diet
Behavioral: Clinical dietician
Counselling from a clinical dietician bi-weekly until weight loss of 5% is achieved.
Behavioral: Weight loss
4 weeks eucaloric diet ~13 MJ/day followed by, 20 weeks hypocaloric diet ~9 MJ/day until 5% weight loss is achieved.
Experimental: Whey Protein High-Protein Diet
4weeks eucaloric intake on high-protein diet with whey protein as primary protein source followed by 20weeks hypocaloric intake on equivalent protein rich diet.
Dietary supplement: High-Protein Diet
Diet consisting of 25E% from assigned protein during eucaloric diet and 35E% from assigned protein during hypocaloric diet
Behavioral: Clinical dietician
Counselling from a clinical dietician bi-weekly until weight loss of 5% is achieved.
Behavioral: Weight loss
4 weeks eucaloric diet ~13 MJ/day followed by, 20 weeks hypocaloric diet ~9 MJ/day until 5% weight loss is achieved.
Placebo Comparator: Normal Diet
4weeks eucaloric diet with normal protein content (15E%) followed by 20weeks hypocaloric intake on equivalent diet.
Behavioral: Clinical dietician
Counselling from a clinical dietician bi-weekly until weight loss of 5% is achieved.
Behavioral: Weight loss
4 weeks eucaloric diet ~13 MJ/day followed by, 20 weeks hypocaloric diet ~9 MJ/day until 5% weight loss is achieved.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Steatosis, absolute
Time Frame: 4 weeks and 20 weeks
Absolute difference in changes in steatosis (MRs) between diets
4 weeks and 20 weeks
Steatosis, relative
Time Frame: 4 weeks and 20 weeks
Relative difference in changes in steatosis (MRs) between diets
4 weeks and 20 weeks
Liver enzymes
Time Frame: 4 weeks and 20 weeks
Difference in change of liver enzymes between diets
4 weeks and 20 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Insulin Secretion
Time Frame: 24 weeks
Changes in Insulin Secretion
24 weeks
Hepatic Insulin Resistance
Time Frame: 24 weeks
Changes in hepatic insulin resistance measured by changes in suppression of EGP from basal period to clamp period.
24 weeks
Adipose tissue Insulin Resistance
Time Frame: 24 weeks
Changes in adipose insulin resistance measured by changes in suppression of lipolysis from basal period to clamp period.
24 weeks
Peripheral insulin resistance
Time Frame: 24 weeks
Changes in peripheral insulin resistance measured total rate of disappearance of glucose in hyperinsulinemic clamp.
24 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Anthropometric measures
Time Frame: 24 weeks
Changes in body composition (Fat mass, lean mass, waist-hip-ratio, BMI)
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Aarhus

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Copenhagen
Hvidovre University Hospital
Arla Foods

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Henning Grønbæk, Prof., University of Aarhus

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 15, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 24, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 9, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 12, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 1, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 26, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DAIPRO-NAFLD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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