The Effects of Coffee Main Constituents (Caffeine and Chlorogenic Acid) Supplementation on Inflammatory, Metabolic Factors, Hepatic Steatosis and Fibrosis in None- Alcoholic Fatty Liver Patients With Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the effects of coffee main constituents (caffeine and chlorogenic acid) supplements on inflammatory, metabolic factors, hepatic steatosis and fibrosis in none- alcoholic fatty liver patients with type 2 diabetes. Two hundred patients with fatty liver and type 2 diabetes will be randomly assigned to one of four groups: group 1, caffeine (200 mg/d) plus chlorogenic acid (200 mg/d); group 2, caffeine (200 mg/d) plus placebo; group 3, chlorogenic acid (200 mg/d) plus placebo; group 4, placebo plus placebo. Supplementation will be daily and will supervise for 6 months.

Conditions
-----------------
Type 2 Diabetes Nonalcoholic Fatty Liver

Intervention / Treatment
-----------------
* Dietary Supplement: caffeine and chlorogenic acid
* Dietary Supplement: caffeine
* Dietary Supplement: chlorogenic acid
* Dietary Supplement: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient diagnosed with type 2 diabetes based on American Diabetes Association (ADA) definition or who only take oral antidiabetic drug. CAPscore >263 Exclusion Criteria: Criteria: Taking any kind of antibiotics two weeks before recruitment; History of alcohol consumption ; pregnancy or lactation; Professional athletes; Other liver disease (viral/etc); High dose synthetic estrogens, methotrexate , amiodarone, steroids, chloroquine, immunosuppressive drugs; A history of Cardiovascular disease; Renal disease, Celiac disease, Cirrhosis; History of Upper Gastrointestinal surgery ; A history of hypothyroidism or Cushing's syndrome; History of drug dependence; Body mass index (BMI) ≥35 kg/m2; A restrictive diet or weight change ≥ 5 kg during the 3 months prior to study; Any change in treatment with oral hypoglycemic; anti hypertensive and antilipid agents during the study; Use of weight loss medications

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: caffeine and chlorogeinc acid<br>caffeine (200 mg) 1 capsule / day for 6 months plus chlorogenic acid (200 mg) 1 capsule / day for 6 months | Dietary Supplement: caffeine and chlorogenic acid<br>* caffeine plus chlorogenic acid<br>|
| Active Comparator: caffeine<br>caffeine (200 mg) 1 capsule / day for 6 months plus placebo (200) mg 1 capsule / day for 6 months | Dietary Supplement: caffeine<br>* caffeine plus placebo<br>|
| Active Comparator: chlorogenic acid<br>chlorogenic acid (200 mg) 1 capsule / day for 6 months plus placebo (200 mg) 1 capsule / day for 6 months | Dietary Supplement: chlorogenic acid<br>* chlorogenic acid plus placebo<br>|
| Placebo Comparator: placebo<br>placebo (200 mg) 1 capsule / day for 6 months plus placebo (200 mg) 1 capsule / day for 6 months | Dietary Supplement: placebo<br>* placebo plus placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatic steatosis | measured by CAP score using Fibroscan | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose |  | 6 months | 
| Glycated hemoglobin (HBA1C) |  | 6 months | 
| alanine aminotransferase (ALT) |  | 6 months | 
| aspartate aminotransferase (ALS) |  | 6 months | 
| High sensitive C reactive protein ( hs- CRP) |  | 6 months | 
| gut microbiota |  | 3 months |