Semaglutide Effects in Obese Youth With Prediabetes/New Onset Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease

Phase 2

Recruiting

• Conditions: Impaired Glucose Tolerance; Type 2 Diabetes Mellitus; Obesity, Childhood; Non-Alcoholic Fatty Liver Disease
• Interventions: Drug: Semaglutide Pen Injector; Drug: Placebo

• Registration Number: NCT05067621
• Lead Sponsor: Yale University

Brief Summary

The purpose of this study is to understand the role of GLP-1 in the pathogenesis of T2D in youth and explore their potential salutary effects and ability to delay the progressive loss of ß-cell function and reduce hepatic steatosis in youth with prediabetes/new onset T2D and NAFLD.

Detailed Description

In a recent publication by the TODAY Group Study, it was reported that "diabetes-related complications appear early in youth-onset T2D and accumulate rapidly at a mean age of 26.4 years," and 60.1% of participants developed at least one microvascular complication. The same has been reported in RISE Studies and was suggested that the rapid decline in β-cell function and its insensitivity to two of the most frequently used treatments for T2D in pediatrics is further aggravated by the rising prevalence in NAFLD. These alarming results indicate a pressing need for effective and innovative approaches at preserving β-cell function and reducing hepatic steatosis in obese youth in order to prevent disease progression and associated complications.

This study will provide mechanistic insights in support of a GLP-1 analog, Semaglutide, 2.4 mg weekly, therapy for prediabetes, new onset T2D and NAFLD in youth. The study design is a randomized, double-blind, placebo-controlled, clinical trial (RCT) using Semaglutie (Wegovy up to 2.4mg) for 6 months followed by a wash-out period of 3 months.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2021-09-21
• Study First Submitted QC: 2021-09-23
• Study First Posted: 2021-10-05
• Study Start: 2023-07-17
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-25
• Last Update Posted: 2024-07-29
• Primary Completion: 2026-12
• Study Completion: 2027-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Receive treatment	Semaglutide Pen Injector	Semaglutide (Wegovy) pen is a subcutaneous injection
Placebo	Placebo	The placebo pen is almost exactly the same as the Wegovy subcutaneous injection except it does not contain the active ingredient, Semaglutide.

Primary Outcome Measures

Name	Time	Method
Change in Oral Disposition Index (oDI)	Baseline and 6 months	The oDI value is the product of total responsivity index and insulin sensitivity. The change in oDI from baseline to 6M on treatment is calculated as the difference between 6M oDI value and baseline oDI value. The oDI measures the ability of beta-cell to respond to a glucose stimulus.
Change in Protein Density Fat Fraction (PDFF)	Baseline and 6 months	The change in PDFF from baseline to 6M on treatment is calculated as the difference between 6M PDFF value and Baseline PDFF. It provides an accurate, non-invasive, reproducible, quantitative, and precise estimation of liver fat content. The expected changes in MRI-PDFF from baseline to 6M is ≥ 5.8% reduction compared to the placebo group.

Secondary Outcome Measures

Name	Time	Method
Triglycerides	9 months	Measures of triglycerides in plasma taken at 9M.
Change in Oral glucose tolerance test (OGTT) derived biomarkers: oDI	Baseline and 9 months	Change in oDI from baseline to 9M after the wash-out period, calculated as the difference between 9M oDI value and baseline oDI value. This is similar to Outcome 1 except measured at 9M.
Change in OGTT derived biomarkers: fasting insulin	Baseline and 9 months	Change in fasting insulin calculated as 1/Fasting Insulin \[1/IF\] from baseline to 9M.
Change in OGTT derived biomarkers: c-peptide	Baseline and 9 months	Change in c-peptide from baseline to 9M calculated as \[change in C-peptide from 0-30min\]; /\[change in glucose from 0-30 min\]. This computes for early c-peptide response to oral glucose.
Change in OGTT derived biomarkers: fasting c-peptide	Baseline and 9 months	Change in fasting c-peptide from baseline to 9M calculated as Fasting C-peptide/Fasting Insulin.
Time to glucose peak	9 months	Identification of time to glucose peak during OGTT at 9M.
Glucagon levels	9 months	Identification of glucagon levels during OGTT at 9M.
Incretin effect	9 months	Estimated as the ratio between total insulin responses during OGTT and IVGTT at the end of the wash-out period and expressed as percentage. It is computed by: \[100% × (AUCins OGTT - AUCins IVGTT)/AUCins OGTT\].
Change in Protein Density Fat Fraction (PDFF)	Baseline and 9 months	The change in PDFF from baseline to 9M after the wash-out period is calculated as the difference between 9M PDFF value and Baseline PDFF. It provides an accurate, non-invasive, reproducible, quantitative, and precise estimation of liver fat content. The expected changes in MRI-PDFF from baseline to 9M is ≥ 5.8% reduction compared to the placebo group.
Fractional rates of de Novo Lipogenesis (DNL)	9 months	It is the measure of contribution of hepatic DNL and plasma free fatty acid reesterification to plasma triglyceride secretion at 9M. It is calculated by F = plasma palmitate enrichment/(22 X plasma deuterium enrichment). F is the fraction of palmitate synthesized during the time between the loading dose of the deuterium-labeled water and the collection time.
Total cholesterol	9 months	Measure of total cholesterol in plasma taken at 9M.
LDL cholesterol	9 months	Measure of LDL cholesterol in plasma taken at 9M.
HDL cholesterol	9 months	Measure of LDL cholesterol in plasma taken at 9M.

Trial Locations

Locations (1)

Pediatric Diabetes Center; 🇺🇸 New Haven, Connecticut, United States