NASHNCT06563921
RE and Probiotics in MAFLD/NAFLD
A study testing physical exercise programme and probiotics supplementation in people with NASH and NAFLD, run by Nicolaus Copernicus University.
Trial summary
This project aims to evaluate the roles of the autonomic nervous system (ANS) and gut microbiota as correlates of clinical improvement in metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic fatty liver disease (NAFLD) in response to a therapeutic regimen comprising resistance exercise and… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- What is being tested?
- physical exercise programme and probiotics supplementation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- No sites listed yet
- Study dates
- 10 Nov 2026to 10 Apr 2036
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of NAFLD/MAFLD or NASH (imaging or histological confirmation of fatty liver disease, e.g., ultrasound, MRI-PDFF, biopsy)
- Age 18-60 years
- Ability to understand the study procedures and provide informed consent.
- Stable clinical condition for at least 3 months prior to study initiation.
Who cannot join
- Lack of fluency in English or Polish
- Significant (structural) limitation of upper and/or lower limb mobility
- Pregnancy or breastfeeding
- Inability to understand instructions
- Shift work
- Participation in any study or research project within the last 3 months
Show all 27Show fewer
- Participation in an interventional drug study within the last 3 months
- Participants with hepatic steatosis and regular alcohol consumption > 30 g/day
- Individuals with any concomitant liver disease (viral hepatitis, drug-induced liver injury, metabolic/genetic diseases (e.g., Wilson's disease))
- Anticoagulant/antiplatelet therapy, antithrombotic therapy, immunosuppressive medications, prolonged immunosuppression (e.g., recent cytotoxic chemotherapy, HIV infection with CD4 count < 240), antibiotics, corticosteroids, valproic acid, amiodarone, tamoxifen within 3 months prior to study enrollment
- Use of medications such as steroids, methotrexate, metformin
- Use of agents such as vitamin E, omega-3 fatty acids, or medications with evidence of an effect on NAFLD (pioglitazone, GLP-1 analogues, dipeptidyl peptidase IV inhibitors, ursodeoxycholic acid)
- Active or previous history of invasive cancer (excluding curatively treated carcinoma in situ [e.g., cervical] or benign skin cancer), unless complete remission has been achieved
- Regular use of probiotic or prebiotic supplements within 3 months prior to study enrollment
- Known allergy to probiotics
- History of using an alternative diet within 3 months prior to study enrollment or changing diet during study entry
- Previous surgery (bariatric surgery, gastric or intestinal resection)
- Parenteral nutrition (TPN) within the last 6 months
- Insulin therapy
- Uncontrolled diabetes
- Cardiovascular disease (e.g., uncontrolled blood pressure, coronary artery disease, NYHA class III-IV heart failure, severe arrhythmias, orthostatic intolerance)
- Nervous system disorders
- Cognitive impairment and dementia
- Osteoporosis/osteopenia
- Active thyroid disease
- Cushing's syndrome
- Any implanted battery-powered device (e.g., AICD, pacemaker, cardiac rhythm recorder, cochlear implant)
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: PRObiotic Mixed With Exercise THErapy USe in MAFLD (PROMETHEUS in MAFLD)
This project aims to evaluate the roles of the autonomic nervous system (ANS) and gut microbiota as correlates of clinical improvement in metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic fatty liver disease (NAFLD) in response to a therapeutic regimen comprising resistance exercise and probiotic supplementation. The primary objective is to investigate the effects of these non-pharmacological interventions on MAFLD/NAFLD and to identify patient phenotypes based on baseline ANS profiles and gut microbiota composition that predict clinical responses.
Read the detailed description
The human microbiome, understood here as the collective community of microorganisms, their genetic material, and metabolic products that colonize the body from birth, is particularly concentrated in the gut. The gut microbiome, dominated primarily by anaerobic bacteria, encompasses thousands of species and millions of genes distributed among the major phyla: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia. Recent research has increasingly focused on the gut microbiome due to its dysbiosis being linked to numerous diseases that may be modifiable through diet, supplementation, or physical activity. Dysbiosis of the gut microbiome has also been implicated in MAFLD and NAFLD, which are the most prevalent liver diseases globally, affecting approximately 35% of the adult population, with this prevalence expected to rise. The gut-liver axis has been extensively studied in relation to MAFLD/NAFLD due to the bidirectional interactions between the gut microbiota and hepatic function. The portal vein, which supplies approximately 70% of the liver's blood flow, facilitates this interaction by connecting the intestines to the liver. Patients with NAFLD/MAFLD typically exhibit increased intestinal permeability compared to healthy individuals, thereby increasing the liver's exposure to gut-derived bacteria, endotoxins, bacterial products, and inflammatory mediators.
Probiotics, defined as live microorganisms that confer health benefits to the host, have been shown in previous studies to enhance the integrity of the intestinal barrier, regulate the gut microbiota, reduce intestinal permeability, and mitigate immune and metabolic disturbances. These effects are particularly relevant in patients with NAFLD/MAFLD, where probiotics have been observed to reduce hepatic steatosis and inflammation-related damage.
Physical exercise, particularly structured programs, has been demonstrated to significantly improve liver function in patients with NAFLD/MAFLD and positively modulate the gut microbiota. Exercise may attenuate the production of reactive oxygen species (ROS) and other oxidative agents in NAFLD by regulating antioxidant enzymes and anti-inflammatory mediators. Additionally, exercise interventions in these patients have been shown to improve blood lipid profiles, including triglycerides, cholesterol, AST, and ALT levels, offering substantial clinical benefits. Although the existing literature predominantly emphasizes aerobic training, this study seeks to compare the effects of resistance training and probiotic supplementation in patients with NAFLD/MAFLD and to assess potential changes in clinical outcomes. Furthermore, the study will explore the influence of baseline ANS and gut microbiota profiles on the patients' responses to these non-pharmacological therapies.
- Being tested
- physical exercise programme, probiotics supplementation, Placebo
- Keywords
- NASH, MAFLD, NAFLD, Probiotics, Resistance training, Gut microbiota, Hypertrophy training
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
physical exercise programmeBehavioural
resistance/hypertrophy-oriented resistance programme
probiotics supplementationDietary supplement
probiotics supplementation
PlaceboDietary supplement
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Experimental: probiotics supplementation + physical exercise program | Experimental | Behavioral: physical exercise program in the form of a resistance/hypertrophy-oriented resistance program Dietary Supplement: probiotics supplementation Receives: Behavioral: physical exercise programme; Dietary Supplement: probiotics supplementation |
| Active Comparator: placebo + resistance/hypertrophy-oriented resistance program plus placebo | Active comparator | placebo + resistance/hypertrophy-oriented resistance program Receives: Behavioral: physical exercise programme; Dietary Supplement: Placebo |
| probiotics supplementation | Experimental | Dietary Supplement: probiotics supplementation Receives: Dietary Supplement: probiotics supplementation |
| placebo | Placebo comparator | placebo Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in liver fat quantified using the ultrasound elastography
Change in liver fat quantified using the ultrasound elastography
Measured: 12 weeks
Secondary outcomes (8)
changes in weight in kilograms using scale
Measured: 12 weeks
changes in body fat mass in kilograms measured using bioelectrical impedance method
Measured: 12 weeks
changes in free-fat mass in kilograms measured using bioelectrical impedance method
Measured: 12 weeks
changes in visceral fat level measured using bioelectrical impedance method
Measured: 12 weeks
HDL cholesterol concentration measured in mg/dL (or mmol/L) using a standardized direct enzymatic assay from fasting venous blood samples
Measured: 12 weeks
LDL cholesterol concentration measured in mg/dL (or mmol/L) using a standardized direct enzymatic assay from fasting venous blood samples
Measured: 12 weeks
Aspartate aminotransferase (AST) activity measured in U/L using a standardized spectrophotometric enzymatic assay from serum samples
Measured: 12 weeks
Alanine aminotransferase (ALT) activity measured in U/L using a standardized spectrophotometric enzymatic assay from serum samples
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2024
- Study start10 Nov 2026 (estimated)
- Primary completion10 Apr 2031 (estimated)
- Study completion10 Apr 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NASHStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nicolaus Copernicus University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford, Medical University of Warsaw
- Responsible party
- Principal investigator, Prof. Paweł Zalewski, PhD, Nicolaus Copernicus University
- Investigators
- Lynette Hodges, PhD, Study chair, Massey University, New ZealandBeata Januszko-Giergielewicz, Assoc. Prof., Study chair, Nicolaus Copernicus University, PolandMaciej Słupski, Prof., Study chair, Nicolaus Copernicus University, PolandKarolina Skonieczna-Żydecka, Prof., Study chair, Pomeranian Medical University in Szczecin, PolandAgnieszka Cudnoch-Jędrzejewska, Prof., Study chair, Warsaw Medical University, PolandSławomir Kujawski, PhD, Study director, Nicolaus Copernicus University, PolandJoanna Słomko, Prof., Study chair, Nicolaus Copernicus University, PolandKarl J. Morten, Prof., Study chair, Oxford University, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06563921
- Sponsor's protocol ID
- MAFLD_NAFLD_probiotics_RE
- Status last verified
- Aug 2026
- First submitted
- 12 Aug 2024
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data would be shared upon a reasonable request from other researches. Requests could be made with a contact Authors after publication of papers on the collected data.
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PRObiotic Mixed With Exercise THErapy USe in MAFLD (PROMETHEUS in MAFLD)
- ClinicalTrials.gov ID
- NCT06563921
- Acronym / sponsor ID
- MAFLD_NAFLD_probiotics_RE
- Keywords
- NASH, MAFLD, NAFLD, Probiotics, Resistance training, Gut microbiota, Hypertrophy training
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Nicolaus Copernicus UniversityUniversity, hospital or other
- Collaborators
- University of Oxford, Medical University of Warsaw
- Study start
- 10 Nov 2026 (estimated)
- Primary completion
- 10 Apr 2031 (estimated)
- Study completion
- 10 Apr 2036 (estimated)
- First posted
- 21 Aug 2024 (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 project aims to evaluate the roles of the autonomic nervous system (ANS) and gut microbiota as correlates of clinical improvement in metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic fatty liver disease (NAFLD) in response to a therapeutic regimen comprising resistance exercise and probiotic supplementation. The primary objective is to investigate the effects of these non-pharmacological interventions on MAFLD/NAFLD and to identify patient phenotypes based on baseline ANS profiles and gut microbiota composition that predict clinical responses.
Detailed description
The human microbiome, understood here as the collective community of microorganisms, their genetic material, and metabolic products that colonize the body from birth, is particularly concentrated in the gut. The gut microbiome, dominated primarily by anaerobic bacteria, encompasses thousands of species and millions of genes distributed among the major phyla: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia. Recent research has increasingly focused on the gut microbiome due to its dysbiosis being linked to numerous diseases that may be modifiable through diet, supplementation, or physical activity. Dysbiosis of the gut microbiome has also been implicated in MAFLD and NAFLD, which are the most prevalent liver diseases globally, affecting approximately 35% of the adult population, with this prevalence expected to rise. The gut-liver axis has been extensively studied in relation to MAFLD/NAFLD due to the bidirectional interactions between the gut microbiota and hepatic function. The portal vein, which supplies approximately 70% of the liver's blood flow, facilitates this interaction by connecting the intestines to the liver. Patients with NAFLD/MAFLD typically exhibit increased intestinal permeability compared to healthy individuals, thereby increasing the liver's exposure to gut-derived bacteria, endotoxins, bacterial products, and inflammatory mediators.
Probiotics, defined as live microorganisms that confer health benefits to the host, have been shown in previous studies to enhance the integrity of the intestinal barrier, regulate the gut microbiota, reduce intestinal permeability, and mitigate immune and metabolic disturbances. These effects are particularly relevant in patients with NAFLD/MAFLD, where probiotics have been observed to reduce hepatic steatosis and inflammation-related damage.
Physical exercise, particularly structured programs, has been demonstrated to significantly improve liver function in patients with NAFLD/MAFLD and positively modulate the gut microbiota. Exercise may attenuate the production of reactive oxygen species (ROS) and other oxidative agents in NAFLD by regulating antioxidant enzymes and anti-inflammatory mediators. Additionally, exercise interventions in these patients have been shown to improve blood lipid profiles, including triglycerides, cholesterol, AST, and ALT levels, offering substantial clinical benefits. Although the existing literature predominantly emphasizes aerobic training, this study seeks to compare the effects of resistance training and probiotic supplementation in patients with NAFLD/MAFLD and to assess potential changes in clinical outcomes. Furthermore, the study will explore the influence of baseline ANS and gut microbiota profiles on the patients' responses to these non-pharmacological therapies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Experimental: probiotics supplementation + physical exercise program | Experimental | Behavioral: physical exercise programme, Dietary Supplement: probiotics supplementationBehavioral: physical exercise program in the form of a resistance/hypertrophy-oriented resistance program Dietary Supplement: probiotics supplementation |
| Active Comparator: placebo + resistance/hypertrophy-oriented resistance program plus placebo | Active comparator | Behavioral: physical exercise programme, Dietary Supplement: Placeboplacebo + resistance/hypertrophy-oriented resistance program |
| probiotics supplementation | Experimental | Dietary Supplement: probiotics supplementationDietary Supplement: probiotics supplementation |
| placebo | Placebo comparator | Dietary Supplement: Placeboplacebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Diagnosis of NAFLD/MAFLD or NASH (imaging or histological confirmation of fatty liver disease, e.g., ultrasound, MRI-PDFF, biopsy)
- Age 18-60 years
- Ability to understand the study procedures and provide informed consent.
- Stable clinical condition for at least 3 months prior to study initiation.
Key exclusion criteria (27 listed)
- Lack of fluency in English or Polish
- Significant (structural) limitation of upper and/or lower limb mobility
- Pregnancy or breastfeeding
- Inability to understand instructions
- Shift work
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 |
|---|---|---|
| physical exercise programmeresistance/hypertrophy-oriented resistance programme | Behavioural | Active Comparator: placebo + resistance/hypertrophy-oriented resistance program plus placebo, Experimental: probiotics supplementation + physical exercise program |
| probiotics supplementationprobiotics supplementation | Dietary supplement | Experimental: probiotics supplementation + physical exercise program, probiotics supplementation |
| PlaceboPlacebo | Dietary supplement | Active Comparator: placebo + resistance/hypertrophy-oriented resistance program plus placebo, placebo |
Primary outcome
Change in liver fat quantified using the ultrasound elastography
Time frame: 12 weeks
Change in liver fat quantified using the ultrasound elastography
8 secondary outcomes
changes in weight in kilograms using scale
Time frame: 12 weeks
changes in body fat mass in kilograms measured using bioelectrical impedance method
Time frame: 12 weeks
changes in free-fat mass in kilograms measured using bioelectrical impedance method
Time frame: 12 weeks
changes in visceral fat level measured using bioelectrical impedance method
Time frame: 12 weeks
HDL cholesterol concentration measured in mg/dL (or mmol/L) using a standardized direct enzymatic assay from fasting venous blood samples
Time frame: 12 weeks
LDL cholesterol concentration measured in mg/dL (or mmol/L) using a standardized direct enzymatic assay from fasting venous blood samples
Time frame: 12 weeks
Aspartate aminotransferase (AST) activity measured in U/L using a standardized spectrophotometric enzymatic assay from serum samples
Time frame: 12 weeks
Alanine aminotransferase (ALT) activity measured in U/L using a standardized spectrophotometric enzymatic assay from serum samples
Time frame: 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2026.
- Individual participant dataSharing planned: Undecided. Data would be shared upon a reasonable request from other researches. Requests could be made with a contact Authors after publication of papers on the collected data.
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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.
Lynette Hodges, PhD study chair
Massey University, New Zealand
Beata Januszko-Giergielewicz, Assoc. Prof. study chair
Nicolaus Copernicus University, Poland
Maciej Słupski, Prof. study chair
Nicolaus Copernicus University, Poland
Questions about this trial
What is this clinical trial studying?
A study testing physical exercise programme and probiotics supplementation in people with NASH and NAFLD, run by Nicolaus Copernicus University.
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 27 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: opening soon, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sławomir Kujawski, PhD (0048791448117, skujawski@cm.umk.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in liver fat quantified using the ultrasound elastography (time frame: 12 weeks). 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 21 Oct 2026.