Clinical trial NCT04871880: Lifestyle Modification for MAFLD Based on TTM
Official title: Lifestyle Modification for the Treatment of Metabolic Associated Fatty Liver Disease Based on Transtheoretical Model: a Single-center, Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Metabolic Associated Fatty Liver Disease
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
First posted: 2021-05-04
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Lifestyle changes aiming at weight loss remain the cornerstone of MAFLD treatment.Evaluating the motivational stage of patients' change and providing targeted lifestyle guidance may significantly improve the efficiency of weight loss. The investigators hypothesize that gut microbiota may affect motivation to lose weight, and the changes in gut microbiota due to weight loss may positively feedback the behavior of motivation, forming a virtuous circle. Thus, this study aims at ①evaluating the relationships between motivational stage of weight loss and the gut microbiota (Gut-brain axis); ②investigating the effects of lifestyle interventions on the gut microbiota in MAFLD patients.

Detailed description: Fatty liver associated with metabolic dysfunction is common, affects a quarter of the population, and has no approved drug therapy. In 2020, two position articles have proposed not only the change of the terminology from NAFLD to metabolic associated fatty liver disease (MAFLD), but also an update and revision of the definition of fatty liver disease. According to these papers, indeed, the diagnosis of MAFLD can be made with the presence of hepatic steatosis (detected by serum biomarker scores, imaging methods or histology) and at least one of the fol- lowing metabolic criteria: (a) overweight/obesity, (b) T2DM and (c) metabolic dysregulation (that means at least two factors among increased waist circumference, hypertension, hypertriglyceridemia, low serum HDL-cholesterol levels, impaired fasting glucose, homeostatic model assessment of insulin resistance \[HOMA-IR\] \> 2.5 or high sensitivity C-reactive protein \> 2 mg/L). Here，the investigators focus on the obese NAFLD, which considered as a sub-phenotype in MAFLD.

Lifestyle changes aiming at weight loss remain the cornerstone of MAFLD treatment. However, it is not easy to make patients change their unhealthy lifestyle. Behavior therapy may only be successful in motivated patients, and motivation to dieting and exercising may be different according to age and sex. Personal motivation for change plays a pivotal role in behavior changes. The transtheoretical model (TTM) is an empirically validated model of individual behavioral change, which involves progress through a series of stages to make a particular behavioral change. TTM-based interventions have been applied to facilitate health behavioral changes, such as physical exercise, smoking cessation, and weight management, studies of which continue to demonstrate positive effects. Evaluating the motivational stage of patients' change and providing targeted lifestyle guidance may significantly improve the efficiency of weight loss. The investigators hypothesize that gut microbiota may affect motivation to lose weight, and the changes in gut microbiota due to weight loss may positively feedback the behavior of motivation, forming a virtuous circle.

Thus, a total of seventy obese patients with NAFLD will be recruited in this study, divided into lifestyle modification program group(n=35) and usual care group(n=35). All subjects will undergo dietary assessment based on Food Frequency Questionnaire ( FFQ) and motivational stages evaluation based on TTM. Stool samples will be collected at each visit. Demographic data will be recorded, consisted of age, weight, height, waist circumference, BMI, and so on. MRI-PDFF will be performed to evaluate liver steatosis. Meanwhile, vibration-controlled transient elastography will be carried out, which include liver stiffness (LSM) and controlled attenuation parameter (CAP) measurements. Biochemistry tests will be conducted as supplementary for assessment of NAFLD and cardiovascular risks, comprising liver function test, lipid, fasting glucose, etc.

The investigators aim at ①evaluating the relationships between motivational stage of weight loss and the gut microbiota (Gut-brain axis); ②investigating the effects of lifestyle interventions on the gut microbiota in MAFLD patients.

Eligibility criteria: Inclusion Criteria:

1. With age range of 18-65 years.
2. BMI ≥ 28kg/m2
3. Fatty infiltration of the liver was confirmed on imaging studies (ultrasound, transient elastography, computed tomography, or magnetic resonance imaging) or liver biopsy.
4. With valid motivational stage assessment based on TTM.
5. Written consent form obtained.

Exclusion Criteria:

1. History of other chronic liver disease (Viral hepatitis B or C, autoimmune hepatitis, cholestatic and Inherited metabolic liver diseases) and hemochromatosis.
2. Self-reported HIV-positive status, active tuberculosis, active malaria, or inflammatory bowel disease.
3. Excessive alcohol consumption (\>30g/d for men and \>20g/d for women).
4. Patient has known cirrhosis (compensated/decompensated) either based on clinical criteria or liver histology or Imaging techniques.
5. Subjects using thyroid hormones, oestrogens, amiodarone, steroids, tamoxifen and other medicine known to affect liver fat accumulation.
6. Subjects using thiazolidinedione hypoglycemic drugs, vitamin E and other medicine have potential benefits for NASH within six months.
7. Subjects with organ failure.
8. Subjects with hepatocellular carcinoma or other active malignancy.
9. Solid organ transplant recipients.
10. Antibiotic treatment within the previous 3 months.
11. Suffering from any acute or chronic cardiovascular, GI or immunological condition.
12. Gastric or duodenal ulcer in the past six months.
13. Currently pregnant or nursing.
14. Concomitant diseases with reduced life expectancy.
15. Combined mental illness.
16. Contraindication to MRI scanning.
17. Exclusions may also be made at the discretion of the attending physician or the eligibility committee.
18. Inability to provide informed consent.

Primary outcomes:
measure: Hepatic fat
timeFrame: 12 months
measure: Obesity
timeFrame: 1, 4, 8, 12, 24 months
measure: Gut microbiota
timeFrame: 1, 4, 8, 12, 24 months
Secondary outcomes:
measure: Blood pressure
timeFrame: 1, 4, 8, 12, 24 months
measure: Central obesity
timeFrame: 1, 4, 8, 12, 24 months
measure: Insulin resistance
timeFrame: 1, 4, 8, 12, 24 months
measure: FPG
timeFrame: 1, 4, 8, 12, 24 months
measure: HbA1c
timeFrame: 1, 4, 8, 12, 24 months
measure: Plasma triglycerides
timeFrame: 1, 4, 8, 12, 24 months
measure: Plasma HDL-cholesterol
timeFrame: 1, 4, 8, 12, 24 months
measure: Plasma high-sensitivity C-reactive protein level
timeFrame: 1, 4, 8, 12, 24 months
measure: Gut microbiota diversity
timeFrame: 1, 4, 8, 12, 24 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
References: