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

NCT ID: NCT05067621

Last Updated: 2025-05-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-17
• Study Completion Date: 2027-01-31

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.

Conditions

Type 2 Diabetes Mellitus; Impaired Glucose Tolerance; Non-Alcoholic Fatty Liver Disease; Obesity, Childhood

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Receive treatment

Semaglutide (Wegovy) pen is a subcutaneous injection

Group Type: EXPERIMENTAL

Semaglutide Pen Injector

Intervention Type: DRUG

Semaglutide (Wegovy) pen is a subcutaneous injection that contains 2.4mg/0.75mL of active ingredient. The injection pen can deliver doses of 0.24mg, 0.5mg, 1.0mg, 1.7mg, and 2.4mg.

Placebo

The placebo pen is almost exactly the same as the Wegovy subcutaneous injection except it does not contain the active ingredient, Semaglutide.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Injection pen contains excipients.

Interventions

Semaglutide Pen Injector

Semaglutide (Wegovy) pen is a subcutaneous injection that contains 2.4mg/0.75mL of active ingredient. The injection pen can deliver doses of 0.24mg, 0.5mg, 1.0mg, 1.7mg, and 2.4mg.

Intervention Type: DRUG

Placebo

Injection pen contains excipients.

Intervention Type: DRUG

Other Intervention Names

Wegovy

Eligibility Criteria

Inclusion Criteria

• Subjects diagnosed with Pre-impaired glucose tolerance (pre-IGT) (2h glucose ≥ 130 mg/dl to ≤ 200 mg/dl post-OGTT) OR impaired glucose tolerance (2h glucose ≥140 to <200 mg/dl post-OGTT OR HbA1c ≥5.7% to <6.5%), OR new-onset T2D (≤24 months duration, 2h glucose >200 and HbA1c >6.5% to10%) treated with stable metformin dose (stable metformin dose is defined as at least 1000 mg daily or the maximum tolerated dose for 12 months or less)
• PDFF of ≥ 8%
• Male or female, aged 10 to <21 years at the day of randomization, in puberty (pubertal stage will be assessed by pediatric Endocrinologists Dr. Samuels and Dr. Hu) (girls and boys: Tanner stage II-IV); girls who begin menstruating must have a negative pregnancy test during the study
• Weight ≥ 54kg
• BMI ≥ 85% but ≤ 40 kg/m2
• Good general health (normal kidney function, amylase, and lipase levels)
• Informed consent from a legally acceptable representative (LAR) and child assent from the subject obtained before any trial-related activities (trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial)
• Ability and willingness to adhere to the protocol including self-measurement of plasma glucose according to the protocol.

• Taking medication, based on the investigator's judgement, that may cause significant weight gain or loss (e.g., antipsychotic, steroid, anti-obesity medication).
• Presence or history of malignant neoplasm within 5 years prior to the day of screening.Basal and squamous cell skin cancer and any carcinoma in-situ is allowed.
• Positive insulinoma associated-protein 2 (IA-2) antibodies or anti-glutamic acid decarboxylase (anti-GAD) antibodies.

Mental health:

• History of major depressive disorder within 2 years before screening
• Diagnosis of other severe psychiatric disorders (e.g., schizophrenia, bipolar disorder)
• A Patient Health Questionnaire-9 (PHQ-9) score of ≥15 at screening
• A lifetime history of suicidal attempt
• Suicidal behavior within 30 days before screening
• Suicidal ideation corresponding to type 4 or 5 based on the Columbia-Suicide Severity
• Rating Scale (C-SSRS) within the past 30 days before screening
• Participants with confirmed diagnosis of bulimia nervosa disorder

Exclusion Criteria

• Known or suspected hypersensitivity to trial product(s) or related products.
• Receipt of any investigational medicinal product within 30 days before screening.
• Prepubertal participants (Tanner stage 1)
• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive methods.
• Having a diagnosis of:

• Type 1 diabetes o Maturity onset diabetes of the young (MODY) o History or presence of Pancreatitis (acute or chronic) o Presence of endocrinopathies (e.g., Cushing syndrome) o Cardiac, renal or pulmonary or other chronic illness o Known history of heart disease (including history of clinically significant arrhythmias or conduction delays on ECG, or new clinically significant arrhythmias or conduction delays on ECG identified at visit 1) o Family or personal history of MEN type 2 or medullary thyroid carcinoma (family is defined as a first-degree relative)o Any other disorder which, in the opinion of the investigator, might jeopardize subject's safety or compliance with the protocol
• Any laboratory safety parameter at screening outside the below extended laboratory ranges: o Baseline creatinine >1.0mg o Hypertriglyceridemia)(>500 mg/dl)

• Calcitonin equal or above 50 ng/L at screening o Body Mass Index (BMI) ≤ 25.0 at the screening visit o ALT ≥5 times the upper normal limit (UNL) o Creatinine >UNL for age in children unless renal function is proven normal by further assessments at the discretion of the investigator
• Known hypoglycemic unawareness.
• Recurrent severe hypoglycemic episodes within the last year as judged by the investigator.
• Uncontrolled hypertension treated or untreated >99th percentile for age and gender in children and adolescents.

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Sonia Caprio

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sonia Caprio, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Pediatric Diabetes Center

New Haven, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Julie Holub

Role: CONTACT

julie.holub@yale.edu

203-785-5692

Theresa Goddard

Role: CONTACT

theresa.goddard@yale.edu

203-785-5692

Facility Contacts

Sonia Caprio, MD

Role: primary

sonia.caprio@yale.edu

2037855692

Alfonso Galderisi, MD

Role: backup

alfonso.galderisi@yale.edu

2037855692

Other Identifiers

2R01DK111038-06A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000031181

Identifier Type: -

Identifier Source: org_study_id