Super HEROES: Searching How the Extract Rebaudioside Occludes Excess Steatosis

In order to determine whether rebaudioside consumption can be used as a treatment for adolescents with Non-alcoholic Fatty Liver Disease (NAFLD) by demonstrating a decrease in alanine aminotransferase (ALT) levels participants will be randomized to receive one of three 8-week liquid diet interventions:

1. Standard of care
2. Water delivery
3. Water with Rebaudioside (stevia natural sweetener)

Study Overview

• Status: Recruiting
• Conditions: Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Other: Water Intervention; Other: Stevia Intervention

Detailed Description

Rationale: Current treatment strategies for Nonalcoholic fatty liver disease, NAFLD, have focused on lifestyle management through a combination of diet and exercise but there are no recommendations for dietary changes that have been proven superior to others. Preliminary data showing an improvement in liver enzymes and fibrosis in mice has demonstrated a novel use of rebaudioside, the non-caloric sweetener (NCS) Stevia leaf's extract, potentially identifying this NCS as a therapeutic intervention where currently there are no targeted treatments.

Intervention: All participants will receive standard of care for diet and nutrition. Additionally, participants will be randomized to one of four 8-week liquid diet interventions:

1. Standard of Care
2. Water Delivery
3. Water with Rebaudioside (Stevia Natural Sweetener)

Objectives and Purpose: To determine whether rebaudioside consumption can be used as a treatment for adolescents with NAFLD by demonstrating a decrease in ALT levels.

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

Contacts and Locations

• Study Contact: Name: Asal Gholikhani, BA; Phone Number: 323-361-1432; Email: agholikhani@chla.usc.edu
• Study Contact Backup: Name: Ronald Martinez; Phone Number: 323-361-3402; Email: rmartinezgalan@chla.usc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hospital of Los Angeles
      • Contact: Asal Gholikhani; Phone Number: 323-361-1432; Email: agholikhani@chla.usc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: 10-18 years
• ALT > 45 IU/L (twice the normal amount)
• BMI >85%
• Fat >5% and kPa> 2.7

Exclusion Criteria:

• Physician diagnosis of a major medical illness including, but not limited to, chronic liver disease, immunodeficiency disorder, hypothalamic obesity, or a genetic cause of obesity.
• Familial hyperlipidemia
• Positive hepatitis lab
• Antibiotics within 1 month of beginning the study
• Physical, mental, or cognitive issues preventing participation
• Pregnancy
• Smoking or drinking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care; The control group will receive standard of care dietary advice for their solid food and beverage intake.
Active Comparator: Water Intervention; We will order and deliver bottled water to the homes of subjects in the treatment group. We will provide each participant with a weekly supply of about 36 16.9 fl oz single-serving containers. We will instruct subjects to notify us by calling a dedicated telephone line on occasions when a delivery is expected but not received so that the problem can be corrected expeditiously.	Other: Water Intervention; Bottled Water
Experimental: Stevia Intervention; We will order and deliver a commercially-available stevia-sweetened soft drink Zevia (Los Angeles, CA) to each participant in the treatment group. We will provide each participant with a weekly supply of 24 12 fl oz single-serving containers. Zevia will be provided in an assortment of flavors for the first week, then catered to the preference of the participant for the remainder of the study. We will instruct subjects to notify us by calling a dedicated telephone line on occasions when a delivery is expected but not received so that the problem can be corrected expeditiously. Participants will also be asked to keep track of how many containers they consume using a sticker chart, and we will also phone parents weekly to verify the sticker charts	Other: Stevia Intervention; We will use commercially available stevia sweetened soft drink Zevia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Alanine Transaminase (ALT)	A fasting blood sample will be taken at baseline and week 8 and assess change over time in all 3 groups	Week 1 to week 8 (IU/L)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fat percentage	Measured using DEXA	week 1 to 8 weeks (%)
Change in kPA levels	Measured using MR elastography (non-sedated study)	week 1 to 8 weeks (kPA)
Change in Height	Height will be measured in duplicate within .5cm.	week 1 to 8 weeks (cm)
Change in Weight	Measured using an electric scale.	week 1 to 8 weeks (kg)
Change in Waist Circumference	Hip-to-waist ratio will be calculated using a measuring tape that does not stretch, measuring twice at hip-level and twice at waist-level and averaging the results	week 1 to 8 weeks (cm)
Change in Acanthosis nigricans skin exam	An Acanthosis Nigricans (AN) skin exam will be performed at each visit. Acanthosis Nigricans is an indicator for disorders of insulin resistance.	week 1 to 8 weeks
Change in Triglyceride levels	measured by fasting blood sample	week 1 to 8 weeks
Change in Glucose Level	Measured by fasting blood samples	Week 1 to week 8 (mg/dl)
Change in Insulin Level	Measured by fasting blood sample	Week 1 to week 8 (UIU/mL)

Collaborators and Investigators

• Sponsor: Children's Hospital Los Angeles
• Investigators: Principal Investigator: Tania Mitsinikos, MD, Children's Hospital Los Angeles; Principal Investigator: Rohit Kohli, MBBS, MS, Children's Hospital Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2019
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: June 6, 2019
• First Submitted That Met QC Criteria: June 12, 2019
• First Posted (Actual): June 13, 2019

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: CHLA-19-00212

Drug and device information, study documents

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