Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44359   clinical trials with a EudraCT protocol, of which   7384   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Exploring Immune Effects of Oral Insulin in Relatives at Risk for Type 1 Diabetes Mellitus

    Summary
    EudraCT number
    		 2016-001923-30
    Trial protocol
    		 IT  
    Global end of trial date
    13 Mar 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Aug 2025
    First version publication date
    14 Aug 2025
    Other versions
    Summary report(s)
    		 TN20.I.04.Adverse Event Summary Report

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    TN-20
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02580877
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND: 76419
    Sponsors
    Sponsor organisation name
    TrialNet
    Sponsor organisation address
    3650 Spectrum Boulevard, Suite 100, Tampa, United States, 33612
    Public contact
    Erica Perri, TrialNet Coordinating Center, 813 3969543, erica.perri@epi.usf.edu
    Scientific contact
    Erica Perri, TrialNet Coordinating Center, 813 39669543, erica.perri@epi.usf.edu
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Mar 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    01 Mar 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Mar 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the immune response to oral insulin in individuals at risk for type 1 diabetes, in order to determine whether it can modulate the autoimmune process that leads to the disease.
    Protection of trial subjects
    The DSMB met regularly during the study and reviewed safety and related information.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Jan 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Italy: 4
    Country: Number of subjects enrolled
    Australia: 6
    Country: Number of subjects enrolled
    United States: 79
    Country: Number of subjects enrolled
    Canada: 3
    Worldwide total number of subjects
    92
    EEA total number of subjects
    4
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    75
    Adolescents (12-17 years)
    13
    Adults (18-64 years)
    4
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were recruited from the TrialNet Natural History Study (TN01) and thus a relative of a proband with T1D..

    Pre-assignment
    Screening details
    		 The initial testing for mIAA and other autoantibodies were done as part of TN01 screening. Those individuals who were mIAA positive were eligible for additional tests (OGTT) as part of TN01 Monitoring visit or this protocol as applicable.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Oral Insulin daily (67.5 mg)
    Arm description
    		 7.5 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given daily for six months 67.5 mg oral insulin crystals daily: human insulin crystals in capsules
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oral Insulin Crystals
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    67.5 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given daily for six months 67.5 mg oral insulin crystals daily: human insulin crystals in capsules

    Arm title
    		 500 mg oral Insulin every other week
    Arm description
    		 500 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given every other week for six months
    Arm type
    		 Experimental

    Investigational medicinal product name
    Oral Insulin Crystals
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    500 mg oral insulin crystals every other week: human insulin crystals in capsules (by mouth or sprinkled on food)

    Number of subjects in period 1
    		Oral Insulin daily (67.5 mg) 500 mg oral Insulin every other week
    Started
    45
    47
    Completed
    44
    43
    Not completed
    1
    4
         Consent withdrawn by subject
    1
    3
         Adverse event, non-fatal
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Oral Insulin daily (67.5 mg)
    Reporting group description
    		 7.5 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given daily for six months 67.5 mg oral insulin crystals daily: human insulin crystals in capsules

    Reporting group title
    500 mg oral Insulin every other week
    Reporting group description
    		 500 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given every other week for six months

    Reporting group values
    		 Oral Insulin daily (67.5 mg) 500 mg oral Insulin every other week Total
    Number of subjects
    		 45 47 92
    Age categorical
    Units: Subjects
        Children (2-11 years)
    		 38 37 75
        Adolescents (12-17 years)
    		 6 7 13
        Adults (18-64 years)
    		 1 3 4
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 8.9 (3.8 to 28.1) 7.9 (3.0 to 43.6) -
    Gender categorical
    Units: Subjects
        Female
    		 20 21 41
        Male
    		 25 26 51
    Relationship to person with type 1 diabetes
    Units: Subjects
        Sibling
    		 34 29 63
        Parent
    		 6 12 18
        Child
    		 1 2 3
        Other
    		 4 4 8
    Glucose Tolerance
    Units: Subjects
        Normal Glucose Tolerance
    		 36 36 72
        Abnormal Glucose Tolerance
    		 9 11 20
    HLA DR3
    Units: Subjects
        Absent
    		 31 27 58
        Present
    		 14 19 33
        Unknown
    		 0 1 1
    HLA DR4
    Units: Subjects
        Absent
    		 22 15 37
        Present
    		 23 31 54
        Unknown
    		 0 1 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Oral Insulin daily (67.5 mg)
    Reporting group description
    		 7.5 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given daily for six months 67.5 mg oral insulin crystals daily: human insulin crystals in capsules

    Reporting group title
    500 mg oral Insulin every other week
    Reporting group description
    		 500 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given every other week for six months

    Primary: Change in GAD65 Autoantibody Titer

    		 Close Top of page
    End point title
    		 Change in GAD65 Autoantibody Titer [1]
    End point description
    Change in autoantibody (GAD65) biomarker of beta cell specific immune response
    End point type
    Primary
    End point timeframe
    13 and 26 weeks after first dose versus baseline
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis is available. The mean change in autoantibody titer was calculated individually for each treatment arm. The two treatment arms were not compared.
    End point values
    		 Oral Insulin daily (67.5 mg) 500 mg oral Insulin every other week
    Number of subjects analysed
    45
    47
    Units: DK Units/mL
    log mean (confidence interval 95%)
        13 weeks
    247 (168 to 363)
    234 (138 to 396)
        26 weeks
    193 (118 to 313)
    196 (121 to 318)
    No statistical analyses for this end point

    Primary: Change in MIAA Autoantibody Titer From Baseline

    		 Close Top of page
    End point title
    		 Change in MIAA Autoantibody Titer From Baseline [2]
    End point description
    Micro-islet autoantibodies (mIAA) autoantibody titers are a measure of of beta cell immune response
    End point type
    Primary
    End point timeframe
    13 and 26 weeks after first doe versus baseline
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis is available. The mean change in autoantibody titer was calculated individually for each treatment arm. The two treatment arms were not compared.
    End point values
    		 Oral Insulin daily (67.5 mg) 500 mg oral Insulin every other week
    Number of subjects analysed
    45
    47
    Units: DK Units/mL
    log mean (confidence interval 95%)
        13 weeks
    0.021 (0.016 to 0.028)
    0.020 (0.015 to 0.028)
        26 weeks
    0.020 (0.015 to 0.028)
    0.017 (0.013 to 0.023)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected over 1 year
    Adverse event reporting additional description
    Additional information regarding all adverse event can be found in the attached document labeled TN20.I.04.Adverse Event Summary Report .
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 CTCAE
    Dictionary version
    4
    Reporting groups
    Reporting group title
    Oral Insulin daily (67.5 mg)
    Reporting group description
    		 67.5 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given daily for six months 67.5 mg oral insulin crystals daily: human insulin crystals in capsules

    Reporting group title
    500 mg oral Insulin every other week
    Reporting group description
    		 500 mg oral insulin crystals in capsules (by mouth or sprinkled on food) given every other week for six months

    Serious adverse events
    		 Oral Insulin daily (67.5 mg) 500 mg oral Insulin every other week
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 47 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Oral Insulin daily (67.5 mg) 500 mg oral Insulin every other week
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    25 / 45 (55.56%)
    24 / 47 (51.06%)
    Surgical and medical procedures
    Surgical and medical procedures
         subjects affected / exposed
    3 / 45 (6.67%)
    1 / 47 (2.13%)
         occurrences all number
    4
    1
    General disorders and administration site conditions
    Fever
         subjects affected / exposed
    4 / 45 (8.89%)
    1 / 47 (2.13%)
         occurrences all number
    6
    1
    flu-like symptoms
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    General disorders and administrative site conditions
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Immune system disorders
    Allergic reaction
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Anaphylaxis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Menorrhagia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Bronchospasm
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 47 (0.00%)
         occurrences all number
    2
    0
    Cough
         subjects affected / exposed
    4 / 45 (8.89%)
    1 / 47 (2.13%)
         occurrences all number
    4
    1
    Nasal congestion
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 47 (2.13%)
         occurrences all number
    1
    2
    Productive cough
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Sore throat
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Psychiatric disorders
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Neutrophil count decreased
         subjects affected / exposed
    4 / 45 (8.89%)
    4 / 47 (8.51%)
         occurrences all number
    7
    8
    White blood cell decreased
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 47 (2.13%)
         occurrences all number
    2
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    njury, poisoning and procedural complications
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Blood and lymphatic system disorders
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Ear and labyrinth disorders
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Middle ear inflammation
         subjects affected / exposed
    0 / 45 (0.00%)
    4 / 47 (8.51%)
         occurrences all number
    0
    5
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Diarrhea
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 47 (2.13%)
         occurrences all number
    1
    1
    Gastrointestinal pain
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Toothache
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    4 / 45 (8.89%)
    2 / 47 (4.26%)
         occurrences all number
    4
    2
    Skin and subcutaneous tissue disorders
    Skin and subcutaneous tissue disorders
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 47 (2.13%)
         occurrences all number
    1
    1
    Endocrine disorders
    Endocrine disorders
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    2
    0
    Hypothyroidism
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Bronchial infection
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 47 (2.13%)
         occurrences all number
    1
    1
    Infections and infestations
         subjects affected / exposed
    4 / 45 (8.89%)
    2 / 47 (4.26%)
         occurrences all number
    5
    2
    Lung infection
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    2
    Otitis externa
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Otitis media
         subjects affected / exposed
    1 / 45 (2.22%)
    2 / 47 (4.26%)
         occurrences all number
    1
    2
    Pharyngitis
         subjects affected / exposed
    7 / 45 (15.56%)
    2 / 47 (4.26%)
         occurrences all number
    10
    2
    Sinusitis
         subjects affected / exposed
    4 / 45 (8.89%)
    0 / 47 (0.00%)
         occurrences all number
    5
    0
    Soft tissue infection
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1
    Tooth infection
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 47 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory infection
         subjects affected / exposed
    3 / 45 (6.67%)
    2 / 47 (4.26%)
         occurrences all number
    3
    2
    Metabolism and nutrition disorders
    Metabolism and nutrition disorders
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 47 (2.13%)
         occurrences all number
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue Sep 09 08:04:13 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA