Wolfram SyndromePhase 2NCT05659368
Tirzepatide Monotherapy in Patients With Wolfram Syndrome Type 1
A Phase 2 study testing Tirzepatide in people with Wolfram Syndrome, run by Ospedale San Raffaele at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Wolfram Syndrome
- What is being tested?
- Tirzepatide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jan 2024to Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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;
- 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.
Who cannot join
- 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;
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- 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;
- 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;
- Breastfeeding;
- Pre-existing ocular disease (corneal or lens diseases and any other retinal or optic nerve non-Wolfram related diseases).
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
IRCCS San Raffaele Scientific Institute
Milan, 20132
Lorenzo Piemonti, MD, piemonti.lorenzo@hsr.it
Giulio Frontino, MD, frontino.giulio@hsr.it
About this study
Official title: 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
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.
Read more
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.
- Conditions
- Wolfram Syndrome
- Being tested
- Tirzepatide
- Keywords
- wolfram syndrome, diabetes, tirzepatide, insulin secretion
- Medical subject headings
- Wolfram Syndrome, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirzepatideDrug
tirzepatide once weekly
| Study group | Role | What they receive |
|---|---|---|
| Interventional group | Experimental | 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). Receives: Drug: Tirzepatide |
What is being measured
The primary outcome is the main question the study is designed to answer.
changing in endogenous insulin production
C-peptide response in the Mixed Meal Tolerance Test (MMTT; change from baseline C-peptide response)
Measured: [Time Frame: month 6±1, month 12±1]
changing in insulin production
mean change from baseline in stimulated 2 hour plasma C-peptide AUC (from MMTT) maximum stimulated plasma C-peptide: the highest value at any time point during the MMTT
Measured: [Time Frame: month 6±1, month 12±1]
Secondary outcomes (5)
glucose variability
change from baseline in average glucose (measured by continuous glucose monitoring)
Measured: [Time Frame: month 6±1, month 12±1]
glycemic variability
change from baseline in coefficient of glucose variation (measured by continuous glucose monitoring)
Measured: [Time Frame: month 6±1, month 12±1]
change in time in range
change from baseline in time in range (measured by continuous glucose monitoring)
Measured: [Time Frame: month 6±1, month 12±1]
change in insulin requirements
change from baseline in mean daily insulin use over the 3 days preceeding the study visits. The mean daily insulin use value will be calculated, in units of U/kg/day, as the mean of the values of amount of insulin used per day on each of the last three consecutive days preceeding each study visits.
Measured: [Time Frame: month 3±1, month 6±1, month 12±1]
change in HbA1c
change from baseline in HbA1c
Measured: [Time Frame: month 3±1, month 6±1, month 12±1]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2022
- Study start1 Jan 2024
- Primary completionOct 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Wolfram SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ospedale San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lorenzo Piemonti, Ospedale San Raffaele
- Investigators
- Lorenzo Piemonti, MD, Principal investigator, Ospedale San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05659368
- Sponsor's protocol ID
- Wolfram Tirzepatide
- Other IDs
- 2022-003853-70, PNRR-MR1-2022-12375914
- Status last verified
- Feb 2024
- First submitted
- 5 Dec 2022
- Last updated
- 22 Feb 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05659368
- Acronym / sponsor ID
- Wolfram Tirzepatide
- Conditions
- Wolfram Syndrome
- Keywords
- wolfram syndrome, diabetes, tirzepatide, insulin secretion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Ospedale San RaffaeleUniversity, hospital or other
- Study start
- 1 Jan 2024 (actual)
- Primary completion
- Oct 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 21 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Interventional group | Experimental | Drug: TirzepatideTirzepatide 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). |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- A definitive diagnosis of Wolfram syndrome, as determined by the following:
- 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;
- 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.
Key exclusion criteria (11 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tirzepatidetirzepatide once weekly | Drug | Interventional group |
Primary outcome
changing in endogenous insulin production
Time frame: [Time Frame: month 6±1, month 12±1]
C-peptide response in the Mixed Meal Tolerance Test (MMTT; change from baseline C-peptide response)
changing in insulin production
Time frame: [Time Frame: month 6±1, month 12±1]
mean change from baseline in stimulated 2 hour plasma C-peptide AUC (from MMTT) maximum stimulated plasma C-peptide: the highest value at any time point during the MMTT
5 secondary outcomes
glucose variability
Time frame: [Time Frame: month 6±1, month 12±1]
glycemic variability
Time frame: [Time Frame: month 6±1, month 12±1]
change in time in range
Time frame: [Time Frame: month 6±1, month 12±1]
change in insulin requirements
Time frame: [Time Frame: month 3±1, month 6±1, month 12±1]
change in HbA1c
Time frame: [Time Frame: month 3±1, month 6±1, month 12±1]
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lorenzo Piemonti, MD principal investigator
Ospedale San Raffaele
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tirzepatide in people with Wolfram Syndrome, run by Ospedale San Raffaele at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lorenzo Piemonti, MD (+390226432706, piemonti.lorenzo@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
changing in endogenous insulin production (time frame: [Time Frame: month 6±1, month 12±1]). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2024.