NCT04841915

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
46

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Mar 2021

Typical duration for not_applicable

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 15, 2021

Completed
9 days until next milestone

First Submitted

Initial submission to the registry

March 24, 2021

Completed
19 days until next milestone

First Posted

Study publicly available on registry

April 12, 2021

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2023

Completed
Last Updated

April 1, 2025

Status Verified

April 1, 2023

Enrollment Period

2.7 years

First QC Date

March 24, 2021

Last Update Submit

March 26, 2025

Conditions

Outcome Measures

Primary Outcomes (3)

  • Steatosis, absolute

    Absolute difference in changes in steatosis (MRs) between diets

    4 weeks and 20 weeks

  • Steatosis, relative

    Relative difference in changes in steatosis (MRs) between diets

    4 weeks and 20 weeks

  • Liver enzymes

    Difference in change of liver enzymes between diets

    4 weeks and 20 weeks

Secondary Outcomes (4)

  • Hepatic Insulin Resistance

    24 weeks

  • Adipose tissue Insulin Resistance

    24 weeks

  • Peripheral insulin resistance

    24 weeks

  • Insulin Secretion

    24 weeks

Other Outcomes (1)

  • Anthropometric measures

    24 weeks

Study Arms (3)

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.

Dietary Supplement: High-Protein DietBehavioral: Clinical dieticianBehavioral: 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.

Dietary Supplement: High-Protein DietBehavioral: Clinical dieticianBehavioral: Weight loss

Normal Diet

PLACEBO COMPARATOR

4weeks eucaloric diet with normal protein content (15E%) followed by 20weeks hypocaloric intake on equivalent diet.

Behavioral: Clinical dieticianBehavioral: Weight loss

Interventions

High-Protein DietDIETARY_SUPPLEMENT

Diet consisting of 25E% from assigned protein during eucaloric diet and 35E% from assigned protein during hypocaloric diet

Micellar Cassein Isolate High-Protein DietWhey Protein High-Protein Diet

Counselling from a clinical dietician bi-weekly until weight loss of 5% is achieved.

Micellar Cassein Isolate High-Protein DietNormal DietWhey Protein High-Protein Diet
Weight lossBEHAVIORAL

4 weeks eucaloric diet \~13 MJ/day followed by, 20 weeks hypocaloric diet \~9 MJ/day until 5% weight loss is achieved.

Micellar Cassein Isolate High-Protein DietNormal DietWhey Protein High-Protein Diet

Eligibility Criteria

Age25 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Aarhus University Hospital, Dept. Hepatology and Gastroenterology

Aarhus N, 8200, Denmark

Location

Hvidovre Hospital

Hvidovre, 2650, Denmark

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver DiseaseMetabolic SyndromeWeight Loss

Interventions

Diet, High-Protein

Condition Hierarchy (Ancestors)

Fatty LiverLiver DiseasesDigestive System DiseasesInsulin ResistanceHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesBody Weight ChangesBody WeightSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet TherapyNutrition TherapyTherapeuticsDietNutritional Physiological PhenomenaDiet, Food, and NutritionPhysiological Phenomena

Study Officials

  • Henning Grønbæk, Prof.

    University of Aarhus

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Masking Details
The participants will be randomized to one of 3 treatment arms. Protein interventions (MCI and WPI) will be blinded to participants and investigators, but controls with regular diet will not be blinded.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 24, 2021

First Posted

April 12, 2021

Study Start

March 15, 2021

Primary Completion

December 1, 2023

Study Completion

December 1, 2023

Last Updated

April 1, 2025

Record last verified: 2023-04

Data Sharing

IPD Sharing
Will not share

Locations