Effects of Sitagliptin in Relatives of T1D Patients (SITA-one)

May 9, 2023 updated by: Paolo Fiorina, MD, University of Milan

Effects of Sitagliptin in Relatives of Patients With Type 1 Diabetes Mellitus, at High Risk of Developing the Disease

Type 1 Diabetes (T1D) is a chronic autoimmune disease, with a genetic background, resulting from the immune-mediated destruction of beta cells of the pancreas. It can lead to fatal short-term and long-term complications, especially if it is diagnosed late. Three stages of the disease can be identified: Stage 1 is defined by the presence of two or more anti-islet autoantibodies (GAD65, ICA, IA-2, ZnT8) with normoglycemia, Stage 2 shows progression to dysglycemia (impaired glucose tolerance) in the setting of two or more anti-islet autoantibodies, Stage 3 occurs when a patient meets ADA criteria for the diagnosis of diabetes. It's been demonstrated that Teplizumab (an Fc receptor nonbinding anti-CD3 monoclonal antibody) delays the transition from pre-symptomatic T1D (stage 2) to overt T1D (stage 3). Also Sitagliptin, a DPP4 inhibitor, has been proved effective in inhibiting inflammation in T1D both in vitro in T1D mice, and in vivo in Latent autoimmune diabetes in adults (LADA) patients. Furthermore, it has been confirmed that Sitagliptin reduces the prevalence of worse forms of acute GVHD after myeloablative allogeneic hematopoietic stem-cell transplantation.

The study aims to investigate if Sitagliptin can have a delaying effect on progression to overt T1D, on the account of its anti-inflammatory properties. The cohort is made of screened relatives of T1D patients, who are classified as high-risk of developing T1D.

Screening relatives of T1D patients for dysglycemia and anti-islet autoantibodies. Selecting the patients in Stage 2 Pre-symptomatic T1D (dysglycemia and at least two types of autoantibodies) and then beginning therapy with Sitagliptin, while monitoring their glucose metabolism with a Continuous Glucose Monitoring (CGM) system.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

70

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20157
        • Asst Fbf Sacco

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 45 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age of the subject between 10 and 45 years
  • Subject (or legal guardian in the case of a minor) is able to provide informed consent
  • If a first degree relative of the proband with T1D must be between 6 and 45 years old (brother, sister, parent, child)
  • If a relative of the proband with T1D is second degree, he must be between 6 and 20 years old (nephew, uncle, aunt, grandfather, grandmother, cousin)
  • Presence of at least two autoantibodies associated with diabetes
  • Impaired glucose tolerance on the OGTT test (fasting glucose greater than 110 mg/dl but less than 126 mg/dl or 2-hour glucose greater than or equal to 140 mg/dl but less than 200 mg/dl or 'OGTT at 30', 60 ', 90' greater than or equal to 200 mg/dl)
  • If the subject is a female with reproductive potential, she must have a negative pregnancy test at the enrollment visit and must agree not to seek pregnancy for at least one year from randomization
  • If the subject is male, he must agree not to seek pregnancies with any partner for at least one year from the randomization
  • The subject must agree to renounce other types of trials during this study
  • Weight at the time of recruitment of at least 26 kg
  • It must be favorable and clinically acceptable to postpone vaccinations with live and attenuated agents for at least one year after treatment

Exclusion Criteria:

  • Type 1 Diabetes Mellitus previously diagnosed or diagnosed during screening investigations
  • Serological evidence of current or past HIV, Hepatitis C, Hepatitis B
  • Changes in blood counts, INR or liver enzymes
  • Being pregnant or breastfeeding
  • Evidence of pancreatic changes in the laboratory
  • Having undergone a previous experimental treatment for Type 1 Diabetes Mellitus
  • Chronic Renal Failure stage IIIa onwards (eGFR <45 ml / min / 1.7 m2)
  • History of previous pancreatitis
  • Lymphopenia (<1000 lymphocytes / µL)
  • Neutropenia (<1500 PMN / µL)
  • Thrombocytopenia (<150,000 platelets / µL)
  • Anemia (Hgb <10 grams / deciliter [g / dL])
  • AST or ALT> 1.5 x ULN
  • Total bilirubin> 1.5 x upper limit of normal (ULN) with the exception of subjects diagnosed with Gilbert's syndrome who may be eligible provided they have no other cause leading to hyperbilirubinemia
  • INR> 0.1 above the upper limit of the norm at the laboratory of the participating center
  • Alterations of Amylase and Lipase due to the pancreas
  • Chronic active infection other than localized skin infections
  • A positive PPD test
  • Vaccination with a live virus within 8 weeks of randomization
  • Vaccination with a killed virus within 4 weeks of randomization
  • Laboratory or clinical evidence of acute EBV or CMV infection
  • Serological evidence of current or past HIV, hepatitis B or hepatitis C infection
  • Being currently pregnant or breastfeeding, or planning to become pregnant
  • Chronic use of steroids or other immunosuppressive agents
  • A history of asthma or atopic disease that requires chronic treatment
  • Untreated hypothyroidism or active Graves' disease at randomization
  • Current use of non-insulin drugs that affect glycemic control
  • Previous OKT®3 or other anti-CD3 treatment
  • Administration of a monoclonal antibody within the year prior to randomization
  • Participation in any type of clinical trial of therapeutic drugs or vaccines in the 12 weeks prior to randomization
  • Any conditions that, in the opinion of the investigator, could interfere with the conduct of the study or with the safety of the subject.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Treatment group
Sitagliptin
Drug: Sitagliptin
The dose of sitagliptin will be established on the basis of the estimated glomerular filtrate: 100 mg in single daily administration (estimated glomerular filtration rate less than or equal to 45 mL / min / 1.73 m2) or 50 mg (estimated glomerular filtration rate 30-45 mL / min / 1.73 m2)
Device: Professional CGM
The sensor records the patient's glucose readings every 15 minutes for up to 14 days.
Placebo Comparator: Control group
Placebo
Device: Professional CGM
The sensor records the patient's glucose readings every 15 minutes for up to 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Rate of new diagnoses of Type 1 Diabetes Mellitus per year
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of participants with adverse effects on Sitagliptin
Time Frame: 3 years
3 years

Other Outcome Measures

Outcome Measure
Time Frame
To study the effects of Sitagliptin on metabolic markers (C-peptide, OGTT, Insulin) over time up to the diagnosis of diabetes
Time Frame: 3 years
3 years
To study the prevalence of T1D, T1D-related Auto-antibodies and Dysglycemia in relatives of T1D patients
Time Frame: 3 years
3 years
Monitor Stage 2 patients with a CGM system (continuous blood glucose detection)
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Milan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

July 1, 2023

Primary Completion (Anticipated)

December 1, 2025

Study Completion (Anticipated)

December 1, 2027

Study Registration Dates

First Submitted

January 20, 2022

First Submitted That Met QC Criteria

January 20, 2022

First Posted (Actual)

February 2, 2022

Study Record Updates

Last Update Posted (Actual)

May 10, 2023

Last Update Submitted That Met QC Criteria

May 9, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 01/2022

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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