Efficacy of Tirzepatide Monotherapy on Endogenous Insulin Production in Patients with Wolfram Syndrome Type 1

The primary objective of this study is to determine the efficacy of **tirzepatide** in increasing endogenous insulin production in patients with Wolfram syndrome type 1 (WS1). This is clinically relevant as WS1 is a rare genetic disorder characterized by insulin-dependent diabetes mellitus, and enhancing endogenous insulin production could potentially modify the disease's progression and improve patient outcomes.

The clinical trial involves participants diagnosed with **Wolfram syndrome type 1**, a rare genetic disorder. The study population includes both male and female subjects, aged 5 years and older, with no upper age limit specified. Participants are required to have a definite diagnosis of Wolfram syndrome, confirmed by documented diabetes mellitus diagnosed before the age of 16 and relevant genetic mutations. The trial includes a vulnerable population, as it involves individuals with a rare genetic condition. Participants must be willing to wear a continuous glucose monitor, and women of childbearing age are included only after a negative pregnancy test and agreement to use effective contraception. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the efficacy of **tirzepatide** in increasing endogenous insulin production in patients with Wolfram syndrome type 1. This study is a randomized, double-blind, controlled trial, conducted over an estimated duration of 14 months, with the recruitment phase expected to commence on May 16, 2024, and conclude by July 15, 2025. Participants will be randomly assigned to receive one of the three dosages of Mounjaro (2.5 mg, 5 mg, or 7.5 mg) administered as a **solution for injection** via subcutaneous use. The trial will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor progress and safety, and a final end-of-study visit to assess the primary endpoint, which is the percentage of participants with a positive response to the mixed-meal tolerance test (MMTT), specifically a C-peptide level at 90 minutes greater than 0.6 ng/ml.

Participants are expected to be involved in the study for a maximum treatment period of 12 months. The inclusion criteria require a definite diagnosis of Wolfram syndrome, age of 5 years or older, and consent from the patient or their legal guardian. Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception. Participants must also be willing to wear a continuous glucose monitor. Conditions that may lead to early termination from the study include non-compliance with the study protocol, adverse events, or withdrawal of consent. The trial is categorized as a Phase 4 study, focusing on the long-term effects and safety of the intervention in a specific patient population.

The clinical trial involves the administration of **tirzepatide**, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, as the experimental medication. Tirzepatide is provided in three different dosages: 2.5 mg, 5 mg, and 7.5 mg, each formulated as a solution for injection in a vial. The pharmaceutical form is a solution for injection, and the route of administration is subcutaneous. The maximum daily dose for each formulation is 2.5 mg, 5 mg, and 7.5 mg, respectively, with a maximum total dose of 15 mg. The treatment period is set for a maximum of 12 weeks. The active substance, tirzepatide, is a protein of other origin, and the product is manufactured by ELI LILLY NEDERLAND B.V.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of tirzepatide to evaluate its efficacy in increasing endogenous insulin production in patients with Wolfram syndrome type 1. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial aims to provide insights into the potential benefits of tirzepatide monotherapy in this specific patient population.

The efficacy of **tirzepatide** in the clinical trial will be assessed by evaluating its ability to increase endogenous insulin production in patients with Wolfram syndrome type 1 (WS1). The primary endpoint for efficacy assessment is the percentage of participants who exhibit a positive response to the Mixed Meal Tolerance Test (MMTT), defined as a C-peptide level greater than 0.6 ng/ml at 90 minutes. This endpoint will be measured using laboratory tests to determine C-peptide levels, which serve as a biomarker for insulin production. The trial is designed to monitor these parameters over a maximum treatment period of 12 weeks, with assessments scheduled at specific timepoints to ensure accurate and reliable data collection. The trial is categorized as a Phase 4 study, focusing on the evaluation of tirzepatide's efficacy in a specific patient population.