NAFLDPhase 4NAFTxNCT04465032
The Effect of Consecutive Fecal Microbiota Transplantation on Non-Alcoholic Fatty Liver Disease (NAFLD)
A Phase 4 study testing Gut microbiome transplantation in people with NAFLD, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
Nonalcoholic fatty liver disease (NAFLD) is a disease of alarmingly increasing prevalence, linked to metabolic, cardiovascular and malignant morbidity and without any officially approved treatment. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- NAFLD
- What is being tested?
- Gut microbiome transplantation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- 10 Dec 2019to 31 Dec 2021
- Phase
- Phase 4
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Obese (BMI > 27 kg/m2)
- Males and postmenopausal females
- Aged 18 to 70 years
- Hepatic steatosis defined as increased hyperechogenicity of the liver on abdominal ultrasound and/or histological signs of steatosis
- Written informed consent
Who cannot join
- Exclusion criteria for MRI (claustrophobia, pacemaker, metal implants, etc)
- Any other liver disease than NAFLD/NASH
- Present excessive alcohol use defined as > 2 units/day
- Recent use (< 3 months) of antibiotics
- use of possible drugs interfering microbiota or recent (< 3 months) changes in dosages
- use of GLP-1 RA or SU-derivatives
Show all 10Show fewer
- Recent (< 3 months) weight change (>5%)
- Cardiovascular co-morbidity defined as heart failure, coronary insufficiency and hypertension in past history
- Previous use of glucocorticosteroids, hormonal substitution, pagitaxel, theofyllin, amiodarone, myelosuppresive agents.
- A psychiatric, addictive or any other disorder that compromises the subjects ability to understand the study content and to give written informed consent for participation in the study
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Leiden University Medical Center
Leiden, 2333 ZA
Maarten Tushuizen, MD, PhD, m.e.tushuizen@lumc.nl
Merel Ruissen, MD, m.m.ruissen@lumc.nl
About this study
Official title: The Effect of Consecutive Fecal Microbiota Transplantation on Non-Alcoholic Fatty Liver Disease (NAFLD) - a Randomized-controlled Trial -
Nonalcoholic fatty liver disease (NAFLD) is a disease of alarmingly increasing prevalence, linked to metabolic, cardiovascular and malignant morbidity and without any officially approved treatment. It is increasingly recognized that the gut microbiome is implicated in the pathogenesis and progression of numerous chronic diseases, including NAFLD. Through the so-called gut-liver axis, the liver is exposed to gut-bacterial-derived products, including toxins (lipopolysaccharides), enzymes (methylamines), alcohol, and short-chain fatty acids (mainly acetate, propionate, and butyrate), that may lead to accumulation of triglycerides, inflammatory responses, oxidative stress and accompanying damage to the hepatocytes. The primary objective is to study the effect of consecutive FMT on liver fat accumulation measured by Magnetic Resonance Images (MRI) LiverMultiscan at 12 weeks. Secondary objectives are weight, waist, blood pressure, metabolic parameters (including glucose, cholesterol, pancreatic beta-cell function, HOMA-IR), objective and subjective stress indicators, gut-microbiota and bile composition and liver enzymes. Stool samples will be collected for microbiota analysis at time point 0, 3, 6 and 12 weeks.
Read the detailed description
Nonalcoholic fatty liver disease (NAFLD) is a disease of alarmingly increasing prevalence, linked to metabolic, cardiovascular and malignant morbidity and without any officially approved treatment. It is increasingly recognized that the gut microbiome is implicated in the pathogenesis and progression of numerous chronic diseases, including NAFLD. Through the so-called gut-liver axis, the liver is exposed to gut-bacterial-derived products, including toxins (lipopolysaccharides), enzymes (methylamines), alcohol, and short-chain fatty acids (mainly acetate, propionate, and butyrate), that may lead to accumulation of triglycerides, inflammatory responses, oxidative stress and accompanying damage to the hepatocytes. The investigators hypothesize that altered gut microbiota underlie (hepatic) insulin resistance and liver fat accumulation in NAFLD patients. Fecal microbiota transplantation, through amelioration of gut-microbiota released products like lipopolysaccharides, short-chain fatty acids, alcohol and enzymes, and changes in bile acids, may positively affect NAFLD.
During the study 20 patients will be randomized for infusion of allogenic (lean donor) or autologous (own) feces by gastroscopy at time points 0, 3 and 6 weeks on a 1:1 basis. Prior to randomization, and at 12 weeks, all patients will undergo LiverMultiscan to non-invasively quantify liver fat accumulation and other features of NAFLD. In addition, various metabolic parameters (lipids, HOMA-IR), objective and subjective stress indicators, gut-microbiota and bile composition, and liver enzymes will be measured.
The primary objective is to study the effect on consecutive FMT on liver fat accumulation measured by Magnetic Resonance Images (MRI) LiverMultiscan at 12 weeks. Secondary objectives are alterations in anthropometrical data (weight, waist, blood pressure), changes in fecal microbiota, liver enzymes, bile composition and metabolic parameters including glucose, lipids, pancreatic beta-cell function and insulin resistance measured as HOMA-IR and objective and subjective stress indicators.
- Conditions
- NAFLD
- Being tested
- Gut microbiome transplantation
- 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.
Gut microbiome transplantationOther
Also called Fecal transplantation
Fecal transplantation will be performed at baseline and at week 3 and 6. At the Department of Clinical Bacteriology either the autologous or allogenic feces is prepared for donation by an experienced lab co-worker. The fecal transplantation will be performed via gastroduodenal endoscopy at the Department of Gastroenterology by an experienced endoscopist. To alleviate the procedure, midazolam is offered to the participants. Following placement of the endoscope in the horizontal duodenum, 150 mL feces solution is inserted via the endoscope.
| Study group | Role | What they receive |
|---|---|---|
| Autologous gut microbiome transplantation | Active comparator | Three autologous (own) fecal transplantations (at baseline, 3 and 6 weeks) Receives: Other: Gut microbiome transplantation |
| Allogenic gut microbiome transplantation | Experimental | Three allogenic (lean donor) fecal transplantations (at baseline, 3 and 6 weeks) Receives: Other: Gut microbiome transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
the effect on consecutive FMT on liver fat accumulation
measured by MRI Livermultiscan
Measured: 12 weeks
Secondary outcomes (16)
alterations in anthropometric data
differences in weight in kilograms
Measured: 3, 6 and 12 weeks
alterations in anthropometric data
differences in systolic and diastolic blood pressure in mmHg
Measured: 3, 6 and 12 weeks
alterations in anthropometric data
differences in waist in centimeters
Measured: 3, 6 and 12 weeks
alterations in pancreatic beta-cell function and insulin resistance
measured by plasma C-peptide in nmol/L derived during OGTT + arginin
Measured: 3, 6 and 12 weeks
alterations in pancreatic beta-cell function and insulin resistance
measured by glucose in mmol/L derived during OGTT + arginin
Measured: 3, 6 and 12 weeks
alterations in pancreatic beta-cell function and insulin resistance
measured by insulin in mU/L derived during OGTT + arginin
Measured: 3, 6 and 12 weeks
alterations in liver enzymes
Aspartaat aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma glutamyl transpeptidase (GGT), alkalic phosphatase (AF), bilirubin
Measured: 3, 6 and 12 weeks
change in bile composition
measured using endoscopic bile samples (qualitative measurements)
Measured: 3 and 6 weeks
change in bacterial species in small intestine and feces
measured by endoscopic duodenal biopsies and fecal samples
Measured: 3 and 6 weeks
changes in lipid homeostasis
cholesterol, HDL, LDL, triglycerides
Measured: 3, 6 and 12 weeks
alterations in psychological stress
by measuring cortisol levels in hair samples
Measured: 0 and 12 weeks
alterations in psychological stress
by reporting psychological stress daily using stress diaries on a scale from 1-10 (non-validated scale)
Measured: week 1, week 4, week 7, week 9 during 7 days
alterations in psychological stress
by Perceived Stres Scale (PSS) questionnaires, scores on a scale from 0-40
Measured: 0 and 12 weeks
changes in physical activity
measuring physical activity by steps with FitBit activity tracker
Measured: during 14 weeks
changes in physical activity
measuring physical activity by active minutes with FitBit activity tracker
Measured: during 14 weeks
changes in physical activity
measuring physical activity by heart rate with FitBit activity tracker
Measured: during 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2020
- Study start10 Dec 2019
- Primary completion31 Mar 2021 (estimated)
- Study completion31 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NAFLDStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blinded randomized controlled trial, randomization 1:1 to allogenic and autologous gut microbiome transplantation
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Dutch Donor Feces Bank, Vedanta Biosciences
- Responsible party
- Principal investigator, metushuizen, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04465032
- Sponsor's protocol ID
- GE17-05
- Acronym
- NAFTx
- Status last verified
- Jul 2020
- First submitted
- 8 Jan 2020
- Last updated
- 9 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Groenewegen B, Ruissen MM, Crossette E, Menon R, Prince AL, Norman JM, Ballieux BEPB, Lamb HJ, Terveer EM, Keller JJ, Tushuizen ME. Consecutive fecal microbiota transplantation for metabolic dysfunction-associated steatotic liver disease: a randomized controlled trial. Gut Microbes. 2025 Dec;17(1):2541035. doi: 10.1080/19490976.2025.2541035. Epub 2025 Aug 4.
PubMed 40755230
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Consecutive Fecal Microbiota Transplantation on Non-Alcoholic Fatty Liver Disease (NAFLD) - a Randomized-controlled Trial -
- ClinicalTrials.gov ID
- NCT04465032
- Acronym / sponsor ID
- NAFTx / GE17-05
- Conditions
- NAFLD
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Dutch Donor Feces Bank, Vedanta Biosciences
- Study start
- 10 Dec 2019 (actual)
- Primary completion
- 31 Mar 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 9 Jul 2020 (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.
Nonalcoholic fatty liver disease (NAFLD) is a disease of alarmingly increasing prevalence, linked to metabolic, cardiovascular and malignant morbidity and without any officially approved treatment. It is increasingly recognized that the gut microbiome is implicated in the pathogenesis and progression of numerous chronic diseases, including NAFLD. Through the so-called gut-liver axis, the liver is exposed to gut-bacterial-derived products, including toxins (lipopolysaccharides), enzymes (methylamines), alcohol, and short-chain fatty acids (mainly acetate, propionate, and butyrate), that may lead to accumulation of triglycerides, inflammatory responses, oxidative stress and accompanying damage to the hepatocytes. The primary objective is to study the effect of consecutive FMT on liver fat accumulation measured by Magnetic Resonance Images (MRI) LiverMultiscan at 12 weeks. Secondary objectives are weight, waist, blood pressure, metabolic parameters (including glucose, cholesterol, pancreatic beta-cell function, HOMA-IR), objective and subjective stress indicators, gut-microbiota and bile composition and liver enzymes. Stool samples will be collected for microbiota analysis at time point 0, 3, 6 and 12 weeks.
Detailed description
Nonalcoholic fatty liver disease (NAFLD) is a disease of alarmingly increasing prevalence, linked to metabolic, cardiovascular and malignant morbidity and without any officially approved treatment. It is increasingly recognized that the gut microbiome is implicated in the pathogenesis and progression of numerous chronic diseases, including NAFLD. Through the so-called gut-liver axis, the liver is exposed to gut-bacterial-derived products, including toxins (lipopolysaccharides), enzymes (methylamines), alcohol, and short-chain fatty acids (mainly acetate, propionate, and butyrate), that may lead to accumulation of triglycerides, inflammatory responses, oxidative stress and accompanying damage to the hepatocytes. The investigators hypothesize that altered gut microbiota underlie (hepatic) insulin resistance and liver fat accumulation in NAFLD patients. Fecal microbiota transplantation, through amelioration of gut-microbiota released products like lipopolysaccharides, short-chain fatty acids, alcohol and enzymes, and changes in bile acids, may positively affect NAFLD.
During the study 20 patients will be randomized for infusion of allogenic (lean donor) or autologous (own) feces by gastroscopy at time points 0, 3 and 6 weeks on a 1:1 basis. Prior to randomization, and at 12 weeks, all patients will undergo LiverMultiscan to non-invasively quantify liver fat accumulation and other features of NAFLD. In addition, various metabolic parameters (lipids, HOMA-IR), objective and subjective stress indicators, gut-microbiota and bile composition, and liver enzymes will be measured.
The primary objective is to study the effect on consecutive FMT on liver fat accumulation measured by Magnetic Resonance Images (MRI) LiverMultiscan at 12 weeks. Secondary objectives are alterations in anthropometrical data (weight, waist, blood pressure), changes in fecal microbiota, liver enzymes, bile composition and metabolic parameters including glucose, lipids, pancreatic beta-cell function and insulin resistance measured as HOMA-IR and objective and subjective stress indicators.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blinded randomized controlled trial, randomization 1:1 to allogenic and autologous gut microbiome transplantation
| Arm | Type | Receives |
|---|---|---|
| Autologous gut microbiome transplantation | Active comparator | Other: Gut microbiome transplantationThree autologous (own) fecal transplantations (at baseline, 3 and 6 weeks) |
| Allogenic gut microbiome transplantation | Experimental | Other: Gut microbiome transplantationThree allogenic (lean donor) fecal transplantations (at baseline, 3 and 6 weeks) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Obese (BMI > 27 kg/m2)
- Males and postmenopausal females
- Aged 18 to 70 years
- Hepatic steatosis defined as increased hyperechogenicity of the liver on abdominal ultrasound and/or histological signs of steatosis
- Written informed consent
Key exclusion criteria (10 listed)
- Exclusion criteria for MRI (claustrophobia, pacemaker, metal implants, etc)
- Any other liver disease than NAFLD/NASH
- Present excessive alcohol use defined as > 2 units/day
- Recent use (< 3 months) of antibiotics
- use of possible drugs interfering microbiota or recent (< 3 months) changes in dosages
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 |
|---|---|---|
| Gut microbiome transplantationAlso: Fecal transplantationFecal transplantation will be performed at baseline and at week 3 and 6. At the Department of Clinical Bacteriology either the autologous or allogenic feces is prepared for donation by an experienced lab co-worker. The fecal transplantation will be performed via gastroduodenal endoscopy at the Department of Gastroenterology by an experienced endoscopist. To alleviate the procedure, midazolam is offered to the participants. Following placement of the endoscope in the horizontal duodenum, 150 mL feces solution is inserted via the endoscope. | Other | Allogenic gut microbiome transplantation, Autologous gut microbiome transplantation |
Primary outcome
the effect on consecutive FMT on liver fat accumulation
Time frame: 12 weeks
measured by MRI Livermultiscan
16 secondary outcomes
alterations in anthropometric data
Time frame: 3, 6 and 12 weeks
alterations in anthropometric data
Time frame: 3, 6 and 12 weeks
alterations in anthropometric data
Time frame: 3, 6 and 12 weeks
alterations in pancreatic beta-cell function and insulin resistance
Time frame: 3, 6 and 12 weeks
alterations in pancreatic beta-cell function and insulin resistance
Time frame: 3, 6 and 12 weeks
alterations in pancreatic beta-cell function and insulin resistance
Time frame: 3, 6 and 12 weeks
alterations in liver enzymes
Time frame: 3, 6 and 12 weeks
change in bile composition
Time frame: 3 and 6 weeks
change in bacterial species in small intestine and feces
Time frame: 3 and 6 weeks
changes in lipid homeostasis
Time frame: 3, 6 and 12 weeks
alterations in psychological stress
Time frame: 0 and 12 weeks
alterations in psychological stress
Time frame: week 1, week 4, week 7, week 9 during 7 days
alterations in psychological stress
Time frame: 0 and 12 weeks
changes in physical activity
Time frame: during 14 weeks
changes in physical activity
Time frame: during 14 weeks
changes in physical activity
Time frame: during 14 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2020.
- Derived from this study: PubMed 40755230Groenewegen B, Ruissen MM, Crossette E, Menon R, Prince AL, Norman JM, Ballieux BEPB, Lamb HJ, Terveer EM, Keller JJ, Tushuizen ME. Consecutive fecal microbiota transplantation for metabolic dysfunction-associated steatotic liver disease: a randomized controlled trial. Gut Microbes. 2025 Dec;17(1):2541035. doi: 10.1080/19490976.2025.2541035. Epub 2025 Aug 4.
- Individual participant dataSharing planned: No
Related trials for NAFLD
Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
Recruiting
NAFLD Clinical Care Pathway
NAFLD, MASLD
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
Non-alcoholic Fatty Liver Disease
RecruitingPhase 2
A Study of Efimosfermin Alfa in Participants With Biopsy-confirmed Cirrhosis (Compensated) Due to MASH
Metabolic Dysfunction-Associated Steatohepatitis, Non-alcoholic Fatty Liver Disease
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Gut microbiome transplantation in people with NAFLD, run by Leiden University Medical Center at 1 site in Netherlands.
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 10 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: status not confirmed, as of the sponsor's last update on 9 Jul 2020. 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 Netherlands. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Maarten Tushuizen, MD PhD (+31 71 5263541, m.e.tushuizen@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the effect on consecutive FMT on liver fat accumulation (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04465032, which also lists 1 linked publication.
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 9 Jul 2020.