Tirzepatide Monotherapy in Patients With Wolfram Syndrome Type 1 (NCT05659368) | Clinical Trial Compass
UnknownPhase 2
Tirzepatide Monotherapy in Patients With Wolfram Syndrome Type 1
Italy10 participantsStarted 2024-01-01
Plain-language summary
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.
Who can participate
Age range
5 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. A definitive diagnosis of Wolfram syndrome, as determined by the following:
. Documented diabetes mellitus diagnosed under 16 completed years according to WHO or ADA criteria AND
. Documented functionally relevant recessive mutations on both alleles of the WFS1 gene or dominant mutation on one allele of the WFS1 gene based on historical test results (if available) or from a qualified laboratory at screening;
. Aged 5 years or older;
. The patient, patient's parent(s), or legally authorized guardian(s) must have voluntarily signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form after all relevant aspects of the study have been explained and discussed with the patient. The guardians' consent and patient's assent, as relevant, must be obtained;
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
. Females of child bearing potential will only be included after a negative highly sensitive urine pregnancy test. If sexually active, they must agree to use a highly effective contraception measure;
. Patient willing to wear a continuous glucose monitor.
Exclusion criteria
. Clinically significant non-Wolfram related CNS involvement which is judged by the Investigator to be likely to interfere with the accurate administration and interpretation of protocol assessments;
. A history of pancreatitis;
. Pre-existing thyroid disease;
. A personal or family history of medullary thyroid carcinoma;
. Multiple Endocrine Neoplasia syndrome type 2;
. Active liver or renal disease, personal or family history of liver/kidney dysfunction related to known genetic disorders;
. Treatment with any investigational drug within the 30 days prior to Trial entry;
. Current therapy with of GLP-1 agonist or DDP-4 inhibitor or a known hypersensitivity to GLP-1 agonist;