NAFLDNCT05699863
The MULTISITE Study
A study testing Lifestyle intervention in people with NAFLD and Obesity, run by Aalborg University Hospital at 1 site in Denmark.
Trial summary
This study will investigate potential correlations and relationships between obesity and organ-specific complications, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic fatty pancreas disease (NAFPD) and fatty kidney. Read more about this study
- Who is it for?
- Ages 30 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- NAFLD, Obesity, Extracellular Vesicles
- What is being tested?
- Lifestyle intervention
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteDenmark
- Study dates
- 6 Oct 2020to 31 Jan 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 30 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 30-60
- BMI between 30,0 - 39,9 kg/m2.
- Signed informed consent.
- Metabolic syndrome
- NAFLD
- Wishes to participate in a weight reduction program.
Who cannot join
- Diabetes or any significant endocrine, heart, kidney, liver, or malignant disease.
- Pregnancy, planned pregnancy, or breast-feeding during the trial.
- Alcohol abuse or abuse of recreational drugs
- Medical treatment (systemic glucocorticoids, steatosis-inducing drugs, antibiotics up to two months prior to inclusion, or chemotherapy) or participation in clinical trials other than this.
- Excessive weight loss within the last three months (defined as more than 10 kilograms).
- Contraindications for MRI and dual energy x-ray absorptiometry (DEXA)scanning.
- Any medical condition or history thereof or any deviation from normal laboratory values that, in the opinion of the investigator, clinically contraindicates or hinders the completion of the trial procedures.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multidisciplinary Approach to Screening for Obesity Complications - The MULTISITE Study
This study will investigate potential correlations and relationships between obesity and organ-specific complications, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic fatty pancreas disease (NAFPD) and fatty kidney. Furthermore, it will investigate how and if a lifestyle-induced weight-loss intervention decreases liver fat and improve NAFLD.
Furthermore, the study will investigate if extracellular vesicles (EVs) can be used as a biomarker for early detection of any of the above-mentioned by comparing obese individuals with NAFLD and metabolic syndrome with both normal weight controls and obese individuals without NAFLD and metabolic syndrome. Lastly, it will investigate if weight changes and the resulting improvement of NAFLD are accompanied by changes in liver-specific extracellular vesicle (EV) phenotypes.
Read the detailed description
The worldwide prevalence of obesity and obesity-associated complications is increasing. A common feature associated with obesity is an increased ectopic and visceral fat inside and around the liver, kidney and pancreas. Ectopic and visceral fat is associated with systemic and local pathologies, including liver disease, pancreas disease, and kidney disease.
Current tools for diagnosis of obesity-related morbidities are insufficient, where methods either have low diagnostic accuracy, are too expensive, or invasive. This limits their use for patient care. Thus, there is a need for suitable non-invasive biomarkers for obesity-related complications that allow for screening, risk-stratification, and treatment evaluation of the growing obese population. In this context, extracellular vesicles (EVs) are of particular interest. EVs are small membrane-encapsulated particles released from cells into the blood circulation, and each EV can be considered a micro-biopsy of one single cell. It is proposed that differences in EV number and phenotype can function as potential biomarkers for obesity-related complications.
Early intervention against obesity and related complications minimizes future diseases. As obesity and its complications are associated with a positive energy balance, the best intervention is increased energy expenditure and/or decreased energy intake , leading to weight loss. Intervention against obesity requires permanent lifestyle changes, which can be helped by e.g., individualised diet and exercise plans, surgery, and counselling.
The aims of this project are thus, 1) to investigate visceral and ectopic fat and its associated complications with focus on NAFLD, NAFPD and fatty kidney. 2) investigate whether EVs can function as potential non-invasive biomarkers for any of these conditions, and 3) investigate if a lifestyle intervention decreases liver visceral and ectopic fat, and whether this improvement is reflected by an improvement of NAFLD and changes in EV phenotypes. The specific aims are as follows:
- Investigate potential correlations and relationships between obesity and organ-specific complications, including NAFLD, NAFPD and fatty kidney;
- Compare obese participants with lean control subjects, and investigate whether organ-specific EVs can be used as a biomarker for early detection of any of the above-mentioned conditions/states;
- Investigate how and if a lifestyle-induced weight-loss intervention decreases liver fat and improve NAFLD. Furthermore, investigate if weight changes and the resulting improvement of NAFLD are accompanied by changes in liver-specific EV phenotypes.
- Conditions
- NAFLD, Obesity, Extracellular Vesicles, Weight Loss
- Being tested
- Lifestyle intervention
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Obesity, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lifestyle interventionBehavioural
Lifestyle intervention in the form of individualised dietitian consultation with the overall goal of weight loss.
Intervention includes one initial consultation with a dietician of 1 hour and 15 minutes where participants receive a personalised diet-plan customised to the participants everyday life. After the initial consultation, the participants attend 10 "follow-ups" of about 25 minutes that are spread out over 4-5 months.
| Study group | Role | What they receive |
|---|---|---|
| Metabolically unhealthy obese (Intervention group) | Experimental | Obese (BMI: 30.0 - 39.9) participants with non-alcoholic fatty liver disease and metabolic syndrome. Receives: Behavioral: Lifestyle intervention |
| Metabolically healthy obese (Comparison group 1) | No intervention | Obese individuals considered metabolically healthy based on them not presenting non-alcoholic fatty liver disease or metabolic syndrome. |
| Healthy normal weight (Comparison group 2) | No intervention | Normal weight individuals without non-alcoholic fatty liver disease or metabolic syndrome. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of weight loss on organ steatosis
Changes in steatosis of the liver, pancreas and kidneys assessed by magnetic resonance imaging (proton density fat fraction) between baseline, during weight loss, and after weight loss.
Measured: 36 months
Effect of weight loss on plasma alanine transaminase
Changes in plasma alanine transaminase (IU/L) between baseline, during weight loss, and after weight loss.
Measured: 36 months
Effect of weight loss on BMI
Changes in BMI between baseline, during weight loss, and after weight loss.
Weight and height will be combined to report BMI in kg/m^2.
Measured: 36 months
Effect of weight loss on total body fat
Changes in total body fat (%) as assessed by dual dual energy x-ray absorptiometry between baseline, during weight loss, and after weight loss.
Measured: 36 months
Effect of weight loss on the homeostasis model assessment for insulin resistance
Changes in Homeostasis model assessment for insulin resistance (HOMA) between baseline, during weight loss, and after weight loss.
Insulin (pmol/L) and plasma glucose (mmol/L) will be combined to calculate HOMA using the iterative structural model.
Measured: 36 months
Effect of weight loss on plasma aspartate transaminase
Changes in plasma aspartate transaminase (IU/L) between baseline, during weight loss, and after weight loss.
Measured: 36 months
Secondary outcomes (2)
Extracellular vesicles as biomarkers in disease monitoring
Changes in extracellular vesicle concentration and phenotype assessed by high-resolution flow cytometry. Changes are defined as differences of extracellular vesicle concentrations and phenotypes between baseline, during weight loss, and after weight loss.
Measured: 36 months
Extracellular vesicles as biomarkers for NAFLD diagnosis
Differences in extracellular vesicle concentration and phenotype assessed by high-resolution flow cytometry between participants with and without NAFLD.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2023
- Study start6 Oct 2020
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Jan 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for NAFLDStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The study has three three groups, including obese (BMI 30,0 - 39,9 kg/m2) individuals (obese group) and lean (BMI 18,5 - 24,9 kg/m2) age and sex-matched control individuals (control group). Based on initial enrolment into the obese group, individuals with NAFLD (\>5% hepatic steatosis) and metabolic syndrome (according to International Diabetes Foundation (IDF) consensus) will undergo a 4-5 month lifestyle intervention (intervention group).
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aalborg University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aase Handberg, Aalborg University Hospital
- Investigators
- Aase Handberg, Prof MD DMSc, Principal investigator, Aalborg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05699863
- Sponsor's protocol ID
- 2020-013
- Status last verified
- Feb 2024
- First submitted
- 19 Apr 2022
- Last updated
- 22 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is a general wish too share Individual Participant Data (IPD), however, due to stringent data and personal data protection considerations, it will not be possible unless data can be fully anonymised in the future.
Publications
Garcia NA, Klove-Mogensen K, Cliff KL, Baek R, Ulanowska M, Quezada JAD, Jorgensen MM, Handberg A, Mellergaard M. Extracellular Vesicle Surface Protein Profiling in Metabolic Dysfunction-associated Steatotic Liver Disease in Obesity. J Extracell Biol. 2026 Sep 1;5(9):e70183. doi: 10.1002/jex2.70183. eCollection 2026 Sep.
PubMed 42683217Ulanowska M, Gjela M, Nielsen MH, Askeland A, Vestergaard P, Frokjaer JB, Hojlund K, Mellergaard M, Handberg A. Dynamic changes in body fat distribution, ectopic fat, and related metabolic improvement in response to weigt loss in obesity. Sci Rep. 2026 Jul 3. doi: 10.1038/s41598-026-57976-3. Online ahead of print.
PubMed 42399294
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multidisciplinary Approach to Screening for Obesity Complications - The MULTISITE Study
- ClinicalTrials.gov ID
- NCT05699863
- Acronym / sponsor ID
- 2020-013
- Conditions
- NAFLD, Obesity, Extracellular Vesicles, Weight Loss
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Aalborg University HospitalUniversity, hospital or other
- Study start
- 6 Oct 2020 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Jan 2036 (estimated)
- First posted
- 26 Jan 2023 (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 study will investigate potential correlations and relationships between obesity and organ-specific complications, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic fatty pancreas disease (NAFPD) and fatty kidney. Furthermore, it will investigate how and if a lifestyle-induced weight-loss intervention decreases liver fat and improve NAFLD.
Furthermore, the study will investigate if extracellular vesicles (EVs) can be used as a biomarker for early detection of any of the above-mentioned by comparing obese individuals with NAFLD and metabolic syndrome with both normal weight controls and obese individuals without NAFLD and metabolic syndrome. Lastly, it will investigate if weight changes and the resulting improvement of NAFLD are accompanied by changes in liver-specific extracellular vesicle (EV) phenotypes.
Detailed description
The worldwide prevalence of obesity and obesity-associated complications is increasing. A common feature associated with obesity is an increased ectopic and visceral fat inside and around the liver, kidney and pancreas. Ectopic and visceral fat is associated with systemic and local pathologies, including liver disease, pancreas disease, and kidney disease.
Current tools for diagnosis of obesity-related morbidities are insufficient, where methods either have low diagnostic accuracy, are too expensive, or invasive. This limits their use for patient care. Thus, there is a need for suitable non-invasive biomarkers for obesity-related complications that allow for screening, risk-stratification, and treatment evaluation of the growing obese population. In this context, extracellular vesicles (EVs) are of particular interest. EVs are small membrane-encapsulated particles released from cells into the blood circulation, and each EV can be considered a micro-biopsy of one single cell. It is proposed that differences in EV number and phenotype can function as potential biomarkers for obesity-related complications.
Early intervention against obesity and related complications minimizes future diseases. As obesity and its complications are associated with a positive energy balance, the best intervention is increased energy expenditure and/or decreased energy intake , leading to weight loss. Intervention against obesity requires permanent lifestyle changes, which can be helped by e.g., individualised diet and exercise plans, surgery, and counselling.
The aims of this project are thus, 1) to investigate visceral and ectopic fat and its associated complications with focus on NAFLD, NAFPD and fatty kidney. 2) investigate whether EVs can function as potential non-invasive biomarkers for any of these conditions, and 3) investigate if a lifestyle intervention decreases liver visceral and ectopic fat, and whether this improvement is reflected by an improvement of NAFLD and changes in EV phenotypes. The specific aims are as follows:
- Investigate potential correlations and relationships between obesity and organ-specific complications, including NAFLD, NAFPD and fatty kidney;
- Compare obese participants with lean control subjects, and investigate whether organ-specific EVs can be used as a biomarker for early detection of any of the above-mentioned conditions/states;
- Investigate how and if a lifestyle-induced weight-loss intervention decreases liver fat and improve NAFLD. Furthermore, investigate if weight changes and the resulting improvement of NAFLD are accompanied by changes in liver-specific EV phenotypes.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- The study has three three groups, including obese (BMI 30,0 - 39,9 kg/m2) individuals (obese group) and lean (BMI 18,5 - 24,9 kg/m2) age and sex-matched control individuals (control group). Based on initial enrolment into the obese group, individuals with NAFLD (>5% hepatic steatosis) and metabolic syndrome (according to International Diabetes Foundation (IDF) consensus) will undergo a 4-5 month lifestyle intervention (intervention group).
| Arm | Type | Receives |
|---|---|---|
| Metabolically unhealthy obese (Intervention group) | Experimental | Behavioral: Lifestyle interventionObese (BMI: 30.0 - 39.9) participants with non-alcoholic fatty liver disease and metabolic syndrome. |
| Metabolically healthy obese (Comparison group 1) | No intervention | –Obese individuals considered metabolically healthy based on them not presenting non-alcoholic fatty liver disease or metabolic syndrome. |
| Healthy normal weight (Comparison group 2) | No intervention | –Normal weight individuals without non-alcoholic fatty liver disease or metabolic syndrome. |
Who may qualify
- Ages
- 30 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Age 30-60
- BMI between 30,0 - 39,9 kg/m2.
- Signed informed consent.
- Metabolic syndrome
- NAFLD
Key exclusion criteria (7 listed)
- Diabetes or any significant endocrine, heart, kidney, liver, or malignant disease.
- Pregnancy, planned pregnancy, or breast-feeding during the trial.
- Alcohol abuse or abuse of recreational drugs
- Medical treatment (systemic glucocorticoids, steatosis-inducing drugs, antibiotics up to two months prior to inclusion, or chemotherapy) or participation in clinical trials other than this.
- Excessive weight loss within the last three months (defined as more than 10 kilograms).
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 |
|---|---|---|
| Lifestyle interventionLifestyle intervention in the form of individualised dietitian consultation with the overall goal of weight loss. Intervention includes one initial consultation with a dietician of 1 hour and 15 minutes where participants receive a personalised diet-plan customised to the participants everyday life. After the initial consultation, the participants attend 10 "follow-ups" of about 25 minutes that are spread out over 4-5 months. | Behavioural | Metabolically unhealthy obese (Intervention group) |
Primary outcome
Effect of weight loss on organ steatosis
Time frame: 36 months
Changes in steatosis of the liver, pancreas and kidneys assessed by magnetic resonance imaging (proton density fat fraction) between baseline, during weight loss, and after weight loss.
Effect of weight loss on plasma alanine transaminase
Time frame: 36 months
Changes in plasma alanine transaminase (IU/L) between baseline, during weight loss, and after weight loss.
Effect of weight loss on BMI
Time frame: 36 months
Changes in BMI between baseline, during weight loss, and after weight loss. Weight and height will be combined to report BMI in kg/m^2.
Effect of weight loss on total body fat
Time frame: 36 months
Changes in total body fat (%) as assessed by dual dual energy x-ray absorptiometry between baseline, during weight loss, and after weight loss.
Effect of weight loss on the homeostasis model assessment for insulin resistance
Time frame: 36 months
Changes in Homeostasis model assessment for insulin resistance (HOMA) between baseline, during weight loss, and after weight loss. Insulin (pmol/L) and plasma glucose (mmol/L) will be combined to calculate HOMA using the iterative structural model.
Effect of weight loss on plasma aspartate transaminase
Time frame: 36 months
Changes in plasma aspartate transaminase (IU/L) between baseline, during weight loss, and after weight loss.
2 secondary outcomes
Extracellular vesicles as biomarkers in disease monitoring
Time frame: 36 months
Extracellular vesicles as biomarkers for NAFLD diagnosis
Time frame: 36 months
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 22 Feb 2024.
- Derived from this study: PubMed 42683217Garcia NA, Klove-Mogensen K, Cliff KL, Baek R, Ulanowska M, Quezada JAD, Jorgensen MM, Handberg A, Mellergaard M. Extracellular Vesicle Surface Protein Profiling in Metabolic Dysfunction-associated Steatotic Liver Disease in Obesity. J Extracell Biol. 2026 Sep 1;5(9):e70183. doi: 10.1002/jex2.70183. eCollection 2026 Sep.
- Derived from this study: PubMed 42399294Ulanowska M, Gjela M, Nielsen MH, Askeland A, Vestergaard P, Frokjaer JB, Hojlund K, Mellergaard M, Handberg A. Dynamic changes in body fat distribution, ectopic fat, and related metabolic improvement in response to weigt loss in obesity. Sci Rep. 2026 Jul 3. doi: 10.1038/s41598-026-57976-3. Online ahead of print.
- Individual participant dataSharing planned: No. There is a general wish too share Individual Participant Data (IPD), however, due to stringent data and personal data protection considerations, it will not be possible unless data can be fully anonymised in the future.
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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.
Aase Handberg, Prof MD DMSc principal investigator
Aalborg University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lifestyle intervention in people with NAFLD and Obesity, run by Aalborg University Hospital at 1 site 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 6 inclusion and 7 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: under way, not looking for participants, as of the sponsor's last update on 22 Feb 2024. 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 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. 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?
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?
Effect of weight loss on organ steatosis (time frame: 36 months). The study lists 6 primary outcomes in all. 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 NCT05699863, which also lists 2 linked publications.
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 22 Feb 2024.