Tirzepatide Monotherapy in Patients With Wolfram Syndrome Type 1

Sponsor
Ospedale San Raffaele
Study ID
NCT05659368
Phase
PHASE2
Status
Unknown

Conditions

  • Wolfram Syndrome

Eligibility Criteria

Sex
ALL
Age
5 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

Wolfram syndrome (WFS:OMIM 222300) is a group of inherited disorders that usually appear in childhood and cause diabetes, optic atrophy leading to loss of vision, deafness and often diabetes insipidus. Wolfram syndrome affected no more than 0.2 in 10,000 people in the European Union. There is no cure and no treatment that will arrest or delay the progress of the disease. The gene responsible for WS1 is WFS1, it encodes for wolframin, a transmembrane glycoprotein involved in the regulation of the unfolded protein response. Recently, drug repurposing has been hypothesized from others and us as being useful for WS1 therapy. More specifically, GLP-1 receptor agonists were suggested as a promising class of anti- diabetic drugs having the potential to delay or even reverse disease progression based on their ability to reduce elevated ER stress in vitro and in vivo. The objective of this project is to create a model of precision-medicine oriented Rare Diabetes Clinic, which will be specifically dedicated to the treatment and follow-up of complex patients with Wolfram Syndrome. A team of clinicians and researchers specialized in diabetes and/or optic neuropathy and with experience in the subset of monogenic forms will make available a cohort of subjects with Wolfram Syndrome prospectively followed in an interventional protocol on the use of tirzepatide (a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist). It will be a prospective phase 2, non-randomized, single group assignment, intervention trial to determine the efficacy of tirzepatide (GIP/GLP-1 receptor agonist) in increasing endogenous insulin production and correcting glycemic lability in patients with Wolfram syndrome type 1 (WS1). The expected outcomes of this study are 1) to provide a therapeutic option for a devastating orphan disease; 2) to confirm the efficacy of a repurposed drug able to reduce elevated endoplasmic reticulum (ER) stress in a disease that represents a model of ER disease; 3) to confirm the efficacy of the disease modeling based on iPSC to predict the response to treatment; 4) to develop a disease-specific multidisciplinary follow-up.

Key Dates

Start date
Jan 1, 2024
Status verified
Feb 2024
Primary completion
Oct 31, 2024
Completion
Dec 31, 2024

Study Design

Enrollment
10 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Interventional group
    Tirzepatide will be injected subcutaneously once-per-week, in the abdomen, thigh or upper arm. To improve gastro-intestinal tolerability, the starting dose will be 5 mg (2.5mg for prepubertal children) and will be increased to a maximum of 15 mg (or highest tolerated dose).

Primary Outcome Measure

changing in endogenous insulin production [ Time Frame: [Time Frame: month 6±1, month 12±1] ]

Central Contacts

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