Tirzepatide Monotherapy in Patients With Wolfram Syndrome Type 1

Last updated: February 21, 2024
Sponsor: Ospedale San Raffaele
Overall Status: Active - Recruiting

Phase

2

Condition

Retinitis Pigmentosa

Treatment

Tirzepatide

Clinical Study ID

NCT05659368
Wolfram Tirzepatide
PNRR-MR1-2022-12375914
2022-003853-70
  • Ages > 5
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. A definitive diagnosis of Wolfram syndrome, as determined by the following:
  2. Documented diabetes mellitus diagnosed under 16 completed years according to WHOor ADA criteria AND
  3. Documented functionally relevant recessive mutations on both alleles of the WFS1gene or dominant mutation on one allele of the WFS1 gene based on historical testresults (if available) or from a qualified laboratory at screening;
  4. Aged 5 years or older;
  5. The patient, patient's parent(s), or legally authorized guardian(s) must havevoluntarily signed an Institutional Review Board/Independent Ethics Committee-approvedinformed consent form after all relevant aspects of the study have been explained anddiscussed with the patient. The guardians' consent and patient's assent, as relevant,must be obtained;
  6. Females of child bearing potential will only be included after a negative highlysensitive urine pregnancy test. If sexually active, they must agree to use a highlyeffective contraception measure;
  7. Patient willing to wear a continuous glucose monitor.

Exclusion

Exclusion Criteria:

  1. Clinically significant non-Wolfram related CNS involvement which is judged by theInvestigator to be likely to interfere with the accurate administration andinterpretation 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 dysfunctionrelated 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 hypersensitivityto GLP-1 agonist;
  9. Any other acute or chronic medical, psychiatric, social situation or laboratory resultthat, based on investigator's judgment, would jeopardize patient safety during trialparticipation, cause inability to comply with the protocol, or affect the Trialoutcome;
  10. Breastfeeding;
  11. Pre-existing ocular disease (corneal or lens diseases and any other retinal or opticnerve non-Wolfram related diseases).

Study Design

Total Participants: 10
Treatment Group(s): 1
Primary Treatment: Tirzepatide
Phase: 2
Study Start date:
January 01, 2024
Estimated Completion Date:
December 31, 2024

Connect with a study center

  • IRCCS San Raffaele Scientific Institute

    Milan, 20132
    Italy

    Active - Recruiting

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