Tirzepatide treatment for Wolfram Syndrome Type 1

Towards a Personalized Precision Medicine in Rare Disease: Tirzepatide (a Dual Glucose-dependent Insulinotropic Polypeptide and Glucagon-like Peptide-1 Receptor Agonist) Monotherapy in Patients With Wolfram Syndrome Type 1

This study is testing if tirzepatide can help manage diabetes and slow down Wolfram Syndrome Type 1 in people who have been diagnosed with this rare condition.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 5 Years and up
• Sex: All
• Sponsor: Ospedale San Raffaele (Academic / other)
• Locations: 1 site (Milan)
• Trial ID: NCT05659368 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of tirzepatide, a GLP-1 receptor agonist, as a monotherapy for patients diagnosed with Wolfram Syndrome Type 1. The study aims to assess the drug's potential to manage diabetes and possibly delay the progression of this rare genetic disorder. Participants must have a confirmed diagnosis of Wolfram syndrome and meet specific eligibility criteria, including age and genetic testing requirements. The trial is designed to contribute to a precision-medicine approach in treating rare diabetes conditions.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 5 years and older with a definitive diagnosis of Wolfram syndrome and documented mutations in the WFS1 gene.

Not a fit: Patients without a confirmed diagnosis of Wolfram syndrome or those with other forms of diabetes may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve diabetes management and potentially slow the progression of Wolfram Syndrome in affected patients.

How similar studies have performed: While the use of GLP-1 receptor agonists in Wolfram syndrome is a novel approach, similar studies in other diabetes contexts have shown promising results.

Eligibility criteria

Inclusion Criteria:

1. A definitive diagnosis of Wolfram syndrome, as determined by the following:

   1. Documented diabetes mellitus diagnosed under 16 completed years according to WHO or ADA criteria AND
   2. 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;
2. Aged 5 years or older;
3. 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;
4. 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;
5. Patient willing to wear a continuous glucose monitor.

Exclusion Criteria:

1. 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;
2. A history of pancreatitis;
3. Pre-existing thyroid disease;
4. A personal or family history of medullary thyroid carcinoma;
5. Multiple Endocrine Neoplasia syndrome type 2;
6. Active liver or renal disease, personal or family history of liver/kidney dysfunction related to known genetic disorders;
7. Treatment with any investigational drug within the 30 days prior to Trial entry;
8. Current therapy with of GLP-1 agonist or DDP-4 inhibitor or a known hypersensitivity to GLP-1 agonist;
9. Any other acute or chronic medical, psychiatric, social situation or laboratory result that, based on investigator's judgment, would jeopardize patient safety during trial participation, cause inability to comply with the protocol, or affect the Trial outcome;
10. Breastfeeding;
11. Pre-existing ocular disease (corneal or lens diseases and any other retinal or optic nerve non-Wolfram related diseases).

Where this trial is running

Milan

• IRCCS San Raffaele Scientific Institute — Milan, Italy (Recruiting)

Study contacts

• Principal investigator: Lorenzo Piemonti, MD — Ospedale San Raffaele
• Study coordinator: Lorenzo Piemonti, MD

Conditions Wolfram Syndrome; wolfram syndrome; diabetes; tirzepatide; insulin secretion