The MULTISITE Study

NCT ID: NCT05699863

Last Updated: 2024-02-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-06
• Study Completion Date: 2036-01-31

Brief 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. 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:

1. Investigate potential correlations and relationships between obesity and organ-specific complications, including NAFLD, NAFPD and fatty kidney;

2. 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;

3. 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metabolically unhealthy obese (Intervention group)

Obese (BMI: 30.0 - 39.9) participants with non-alcoholic fatty liver disease and metabolic syndrome.

Group Type: EXPERIMENTAL

Lifestyle intervention

Intervention Type: BEHAVIORAL

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.

Metabolically healthy obese (Comparison group 1)

Obese individuals considered metabolically healthy based on them not presenting non-alcoholic fatty liver disease or metabolic syndrome.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Healthy normal weight (Comparison group 2)

Normal weight individuals without non-alcoholic fatty liver disease or metabolic syndrome.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Lifestyle intervention

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.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Aalborg University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Aase Handberg

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Aase Handberg, Prof MD DMSc

Role: PRINCIPAL_INVESTIGATOR

Aalborg University Hospital

Locations

Aalborg University Hospital

Aalborg, North Jutland, Denmark

Countries

Denmark

Other Identifiers

2020-013

Identifier Type: -

Identifier Source: org_study_id