Effect of Polyphenol Supplementation on Hepatic Steatosis and Vascular Compliance

Study Overview
=================
Brief Summary
-----------------
The main objective is to study the effect of polyphenol supplementation on hepatic steatosis as measured by hepatic ultrasound, hepatic magnetic resonance imaging and on intima-media thickness and vascular elastography in obese adolescents known for hepatic steatosis as diagnosed by liver biopsy

Detailed Description
-----------------
Evaluate the feasibility of a larger, open-label, randomized, controlled trial on the effects of polyphenol supplementation: Recruitment, compliance to polyphenol supplementation and the visit roadmaps Duration of the radiological exams and participants' satisfaction and point of view on the experience. Test the relevance of using a food diary. Test the effectiveness of the data collection procedure during the visits. Explore the obstacles encountered while performing the radiological exams and the rate of adverse events (AE). Calculate the sample size of the future randomized clinical study Effects of polyphenols IMT and vascular elastography. Anthropometric measurements, insulin resistance, inflammation, lipid/lipoprotein profile, gut microbiome and liver function Evaluated different imaging modality for steatosis Different imaging modalities will be compared between children

Official Title
-----------------
The Effects of Polyphenol Supplementation on Hepatic Steatosis, Intima-media Thickness and Non-invasive Vascular Elastography in Obese Adolescents

Conditions
-----------------
Obesity, Childhood, Hepatic Steatosis, Intimal Hyperplasia

Intervention / Treatment
-----------------
* Dietary Supplement: Effect of polyphenols on hepatic steatosis and vascular elastography and intima media thickness


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 12 to 18 years BMI percentile > 85th for age and sex Diagnosis of hepatic steatosis on imaging (ultrasound or MR). Diagnosis of hepatic steatosis, NASH, or fibrosis on liver biopsy. Elevated alanine aminotransferase (ALT) enzyme level. Index of hepatic steatosis 8xALT/AST + BMI (+2 for girls) > 30. Fatty liver infiltration index (FLI) = e0.953logTG + 0.139IMC + 0.718logGGT + 0.053 abdominal circumference-15.745x 100 > 60. Exclusion Criteria: Known chronic systematic diseases Any other serious conditions which, according to the doctor's judgment, would prevent compliance and safe participation in the study until completion. Exclusion criteria to be validated when contacting the participants and their parents/tutors: Being pregnant. Taking all kinds of prescription or over-the-counter natural health products/natural supplements/vitamins on an ongoing basis or within the next four months, excluding vitamin D. Weight loss of 5% to 10% of the usual weight in the last six months before recruitment or weight change of 5% in the last three months. Alcohol consumption > two drinks/day or > one day/week. Known peanut allergy and/or to the medicinal ingredients contained in the active polyphenol supplement: elderberry, haskap, black chokeberry, blueberry, blackcurrant. Any contraindications for MRI.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Polyphenol supplementation<br>120mg per day of powder polyphenol for 60 days | Dietary Supplement: Effect of polyphenols on hepatic steatosis and vascular elastography and intima media thickness<br>* Measurement of effect of polyphenol supplementation vs placebo on hepatic steatosis and vascular elastography and intima media thickness<br>|
| Placebo Comparator: Placebo<br>1 tab PO QD per day of placebo for 60 days | Dietary Supplement: Effect of polyphenols on hepatic steatosis and vascular elastography and intima media thickness<br>* Measurement of effect of polyphenol supplementation vs placebo on hepatic steatosis and vascular elastography and intima media thickness<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment | Rate of recruitment | Through study completion an average of 1 year | 
| Retention: | The percentage of adolescents who agree to participate in the study and the retention | Through study completion an average of 1 year | 
| Compliance with polyphenol supplementation | Percentage of compliance | Through study completion an average of 1 year | 
| Effectiveness of the data collection procedure during the visits | Percentage of completed visits | Through study completion an average of 1 year | 
| Adverse event | Percentage of adverse events | Through study completion an average of 1 year | 
| Satisfaction of the participants and their point of view on the experience | Percentage of satisfaction of participants enrolled | Through study completion an average of 1 year | 
| Sample size calculation for a randomized controlled study | A sample size for a future randomized controlled study will be calculated from the estimates obtained during this pilot study. | Through study completion an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hepatic steatosis MR | mDixonQuant in percentage | At recruitment, after 60 days, and after 120 days | 
| Change in hepatic steatosis B-mode US | US liver echogenicity normal or increased | At recruitment, after 60 days, and after 120 days | 
| Change in intima media thickness (vascular compliance) | Measurement of carotid artery intima media thickness in mm | At recruitment, after 60 days, and after 120 days | 
| Metabolic syndrome | Insulin resistance evaluated by HOMA-IR mg\dl | At recruitment, after 60 days, and after 120 days | 
| Cholesterol | Triglyceride index (no unit) | At recruitment, after 60 days, and after 120 days | 
| Anthropometric measure | Body mass index | At recruitment, after 60 days, and after 120 days | 
| Inflammatory marker 1 | CRP | At recruitment, after 60 days, and after 120 days | 
| Inflammatory marker 2 | TNF alpha | At recruitment, after 60 days, and after 120 days | 
| Inflammatory marker 3 | IL-6 | At recruitment, after 60 days, and after 120 days | 
| Lipid markers 1 | Triglycerides | At recruitment, after 60 days, and after 120 days | 
| Lipid markers 2 | LDL | At recruitment, after 60 days, and after 120 days | 
| Lipid markers 3 | HDL | At recruitment, after 60 days, and after 120 days | 
| Lipid markers 4 | Apo AI | At recruitment, after 60 days, and after 120 days | 
| Lipid markers 5 | Apo B-100 | At recruitment, after 60 days, and after 120 days | 
| Lipid markers 6 | Adiponectin, leptin | At recruitment, after 60 days, and after 120 days | 
| Liver function test | ALT | At recruitment, after 60 days, and after 120 days | 
| Stool test | Gut microbiome composition | At recruitment, after 60 days, and after 120 days |