Effect of Polyphenol Supplementation on Hepatic Steatosis and Vascular Compliance

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

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

Study Overview

• Status: Recruiting
• Conditions: Obesity, Childhood; Hepatic Steatosis; Intimal Hyperplasia
• Intervention / Treatment: Dietary supplement: Effect of polyphenols on hepatic steatosis and vascular elastography and intima media thickness

Detailed Description

1. 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

2. Effects of polyphenols IMT and vascular elastography. Anthropometric measurements, insulin resistance, inflammation, lipid/lipoprotein profile, gut microbiome and liver function
3. Evaluated different imaging modality for steatosis Different imaging modalities will be compared between children

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Principal investigator; Phone Number: 5143454931; Email: ramy.el-jalbout.hsj@ssss.gouv.qc.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T1C5
      • Recruiting
      • CHU Sainte-Justine
      • Contact: Ramy El Jalbout, MD; Email: ramy.jalbout@gmail.com
      • Contact: Anik Cloutier, MSc; Email: anik.cloutier2.hsj@ssss.gouv.qc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Polyphenol supplementation; 120mg per day of powder polyphenol for 60 days	Dietary supplement: Effect of polyphenols on hepatic steatosis and vascular elastography and intima media thickness; Measurement of effect of polyphenol supplementation vs placebo on hepatic steatosis and vascular elastography and intima media thickness
Placebo Comparator: Placebo; 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; Measurement of effect of polyphenol supplementation vs placebo on hepatic steatosis and vascular elastography and intima media thickness

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
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
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
Compliance with polyphenol supplementation	Percentage of compliance	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

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
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
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
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

Collaborators and Investigators

• Sponsor: St. Justine's Hospital
• Investigators: Principal Investigator: Ramy El Jalbout, MD MSc, St. Justine's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 12, 2019
• First Submitted That Met QC Criteria: June 18, 2019
• First Posted (Actual): June 21, 2019

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Fatty Liver; Pediatric Obesity; Hyperplasia
• Other Study ID Numbers: 2019-2278

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No