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Diabetes Mellitus, Type 1Phase 2NCT03364868

GPPAD-POInT (Global Platform of Autoimmune Diabetes - Primary Oral Insulin Trial)

A Phase 2 study testing Oral Insulin in people with Diabetes Mellitus, Type 1, run by Technical University of Munich at 7 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The GPPAD-POInT Study is designed as a randomized, placebo-controlled, double blind, multicentre, multinational primary prevention phase IIb study aiming to induce immune tolerance to beta-cell autoantigens through regular exposure to oral insulin for a period of 29 to 32 months. Read more about this study

Who is it for?
Ages 4 to 7 monthsHealthy volunteers can take part
Conditions the study is for
Diabetes Mellitus, Type 1
What is being tested?
Oral Insulin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,050 participants
Where
7 sitesin 5 countries
Study dates
7 Feb 2018to 28 Jun 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 4 to 7 months
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • 1. Infant between the ages of 4 months and 7 months at the time of randomization.
  • 2. A high genetic risk (>10%) to develop beta-cell autoantibodies by age 6 years:
  • For infants without a first degree family history of type 1 diabetes, high genetic risk is defined as a DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype, and a genetic risk score that is >14.4.
  • For infants with a first degree family history of type 1 diabetes, high genetic risk is defined as having HLA DR4 and DQ8, and none of the following protective alleles: DRB1*1501, DQB1*0503.
  • Solid foods introduced into diet of infant
  • Written informed consent signed by the custodial parent(s).

Who cannot join

  • Concomitant disease or treatment that may interfere with the assessments, as judged by the investigators.
  • Any condition that could be associated with poor compliance.
  • Any medical condition or medical condition coexisting, which, in the opinion of the investigator, may jeopardize the participant's safe participation in the study.
  • Diagnosis of diabetes at the time of recruitment.
  • Participation in another clinical trial.

Trial locations and contacts

7 sites in 5 countries.

7 sites in 5 countries

Germany3 sites

  • Klinik und Poliklinik f. Kinder und Jugendmedizin, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, CRTD/DFG-Forschungszentrum für Regenerative Therapien, Dresden, Germany

    Dresden, Saxony, 01307

  • AUF DER BULT, Kinder- und Jugendkrankenhaus, Hanover, Germany

    Hanover, Lower Saxony, 30173

  • Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

    Munich, Bavaria, 80804

Other trials in Germany

Belgium1 site

  • University Hospitals Leuven, Faculty of Medicine, Catholic University of Leuven, Leuven, Belgium

    Leuven, 3000

Other trials in Belgium

Poland1 site

  • Medical University of Warsaw, Department of Paediatrics, Warsaw, Poland

    Warsaw, 00-001

Other trials in Poland

Sweden1 site

  • Lund University Dep. of Clinical Sciences Malmo, Skane University Hospital SUS, University Hospital MAS, Malmo, Sweden

    Malmö, 202 13

Other trials in Sweden

United Kingdom1 site

  • Department of Paediatrics Clinical Vaccine Research and Immunisation Education, Children's Hospital, Headington, Oxford, UK

    Oxford, OX3 9DU

Other trials in United Kingdom

About this study

Official title: Oral Insulin Therapy for Prevention of Autoimmune Diabetes

The GPPAD-POInT Study is designed as a randomized, placebo-controlled, double blind, multicentre, multinational primary prevention phase IIb study aiming to induce immune tolerance to beta-cell autoantigens through regular exposure to oral insulin for a period of 29 to 32 months. The hypothesis is that regular exposure to oral insulin throughout the period in life where beta-cell autoimmunity usually initiates will tolerize against insulin and train the body's immune system to recognize the treatment product without reacting adversely to it in a manner seen in children who develop T1D. This immune tolerance induction therapy would reduce the likelihood of beta-cell autoimmunity. The study objective is to determine whether daily administration of oral insulin from age 4 months - 7 months until age 3.00 years to children with elevated genetic risk for type 1 diabetes reduces the cumulative incidence of beta-cell autoantibodies and diabetes in childhood.

Read the detailed description

The GPPAD-POInT-Study aims to determine whether daily administration of oral insulin to children from age 4 months - 7 months with elevated genetic risk for type 1 diabetes reduces the cumulative incidence of beta-cell autoantibodies and diabetes in childhood. The purpose of the GPPAD-POInT-Study is to induce immune tolerance to beta-cell autoantigens through regular exposure to oral insulin for a period of 29 to 32 months. Together with the results of the Pre-POINT-Early Study, this phase IIb study aims to investigate and consolidate the findings from the pilot Pre-POINT Study, namely safety and immune efficacy at a daily dose of 67.5 mg oral insulin. Since babies and young children will be tested in the GPPAD-POInT-Study, the 67.5 mg dose will be reached by dose escalation starting at 7.5 mg for 2 months, followed by exposure to 22.5 mg for 2 months, and reaching the desired 67.5 mg dose. The GPPAD-POInT-Study aims to recruit 1040 children into the trial.

The active substance for oral application is human insulin. Oral Insulin will be applied as a capsule containing 7.5, 22.5 and 67.5 mg of the active substance together with filling substance microcrystalline cellulose.

Being tested
Oral Insulin, Placebo
Keywords
Type 1 diabetes, T1D, diabetes mellitus, oral insulin, oral tolerance, autoantigen, self tolerance, prevention, at risk for developing type 1 diabetes, juvenile diabetes, autoimmune diabetes
Medical subject headings
Diabetes Mellitus, Type 1, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oral InsulinDrug

    treatment starting at 4 months - 7 months until age 3.0 years; dose escalation scheme: daily treatment with 7.5 mg or placebo for 2 months; increasing to daily treatment with 22.5 mg or placebo for the following 2 months; increasing to daily treatment with 67.5 mg or placebo until the end of the treatment period.

  • PlaceboOther

    treatment starting at age 4 months - 7 months until age 3.0 years; daily treatment with insulin or placebo capsules containing filling substance (microcrystalline cellulose).

Study groups in NCT03364868
Study groupRoleWhat they receive
oral insulin capsule (dose escalation using 3 dose strengths)ExperimentalDose 1 is 7.5 mg rH-insulin crystals; dose 2 is 22.5 mg rH-insulin crystals; dose 3 is 67.5 mg rH-insulin crystals. The insulin crystals are formulated together with filling substance (microcrystalline cellulose to a total weight of 200 mg) and contained in hard gelatine capsules. The study treatment will be given orally.
Receives: Drug: Oral Insulin
Placebo capsulePlacebo comparatorDaily treatment with placebo capsules containing filling substance (microcrystalline cellulose).
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The development of persistent confirmed multiple beta-cell autoantibodies

    development of persistent confirmed multiple beta-cell autoantibodies (defined as confirmed IAA, confirmed GADA, confirmed IA-2A, or confirmed ZnT8A in two consecutive samples, AND a confirmed second antibody from these four antibodies in one sample.

    Measured: elapsed time from treatment assignment (baseline) to first positive sample visit (>2 beta-cell antibodies) in children who develop persistent confirmed multiple beta-cell antibodies. Primary outcome can develop any time up to last study visit at 7.5 yrs

  2. The development of diabetes

    OGTT criteria or clinical criteria for diabetes as defined by the American Diabetes Association (ADA).

    Measured: elapsed time from random treatment assignment (baseline) to the development diabetes (date of diagnosis). This primary outcome measure can develop any time during treatment or follow-up period up to the last study visit at 7.5 years of age

Secondary outcomes (4)

  1. Any persistent confirmed beta-cell autoantibody or diabetes

    At least one confirmed autoantibody, in two consecutive samples, including GADA, IA-2A, IAA, ZnT8A, or TS7A, or diabetes as defined by the American Diabetes Association (ADA).

    Measured: elapsed time from treatm. assignm. (baseline) to 1st pos. sample for >1 beta-cell antibody in children who developed persist. confirm. beta-cell antibodies OR diabetes onset, whichever is first. outcome can develop any time up to last visit at 7.5 yr

  2. Persistent confirmed IAA.

    Confirmed IAA in two consecutive samples.

    Measured: elapsed time from treatment assignment (baseline) to first sample that is positive for IAA in children who develop persistent confirmed IAA. Outcome can develop any time during treatment or follow-up period up to the last study visit at 7.5 years of age.

  3. Persistent confirmed GADA.

    Confirmed GADA in two consecutive samples.

    Measured: elapsed time from treatment assignment (baseline) to the first sample that is positive for GADA in children who develop persistent confirmed GADA. Outcome can develop any time up to the last study visit at 7.5 years of age

  4. Abnormal glucose tolerance (AGT) defined by dysglycemia or diabetes.

    Dysglycemia is defined as impaired fasting plasma glucose of ≥110 mg/dL (6.1 mmol/L), or impaired 2-hour glucose of ≥140 mg/dL (7.8 mmol/L), or high glucose levels at intermediate time points on OGTT (30, 60, 90 min) levels of ≥200mg/dL (11.1 mmol/L)). Diabetes is defined according to the criteria of the American Diabetes Association (ADA).

    Measured: elapsed time from treatment assignment to the date at which abnormal glucose tolerance or diabetes is diagnosed. Outcome can develop any time up to the last study visit at 7.5 years of age

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Dec 2017
  2. Study start7 Feb 2018
  3. Primary completion28 Jun 2024
  4. Study completion28 Jun 2024

Resources

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
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,050 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03364868
Sponsor's protocol ID
GPPAD-03-POInT
Status last verified
Oct 2024
First submitted
13 Nov 2017
Last updated
8 Oct 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Ziegler AG, Achenbach P, Weiss A, Berner R, Casteels K, Elding Larsson H, Haupt F, Hommel A, Jacobs A, Kordonouri O, Lundgren M, Oltarzewski M, Pfirrmann M, Snape MD, Szypowska A, Todd JA, Vatish M, von dem Berge T, Winkler C, Bonifacio E; GPPAD-POInT Study Group. Efficacy of once-daily, high-dose, oral insulin immunotherapy in children genetically at risk for type 1 diabetes (POInT): a European, randomised, placebo-controlled, primary prevention trial. Lancet. 2025 Nov 29;406(10519):2564-2576. doi: 10.1016/S0140-6736(25)01726-X. Epub 2025 Nov 11.

    PubMed 41237794

  • Jacobsen LM, Schatz DA. Insulin immunotherapy for pretype 1 diabetes. Curr Opin Endocrinol Diabetes Obes. 2021 Aug 1;28(4):390-396. doi: 10.1097/MED.0000000000000648.

    PubMed 34091488

  • Ziegler AG, Achenbach P, Berner R, Casteels K, Danne T, Gundert M, Hasford J, Hoffmann VS, Kordonouri O, Lange K, Elding Larsson H, Lundgren M, Snape MD, Szypowska A, Todd JA, Bonifacio E; GPPAD Study group. Oral insulin therapy for primary prevention of type 1 diabetes in infants with high genetic risk: the GPPAD-POInT (global platform for the prevention of autoimmune diabetes primary oral insulin trial) study protocol. BMJ Open. 2019 Jun 28;9(6):e028578. doi: 10.1136/bmjopen-2018-028578.

    PubMed 31256036

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Oral Insulin in people with Diabetes Mellitus, Type 1, run by Technical University of Munich at 7 sites in 5 countries.

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 6 inclusion and 5 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: finished, as of the sponsor's last update on 8 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Germany, Belgium, Poland, Sweden, United Kingdom. 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. Some participants in this study may receive a placebo. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The development of persistent confirmed multiple beta-cell autoantibodies (time frame: elapsed time from treatment assignment (baseline) to first positive sample visit (>2 beta-cell antibodies) in children who develop persistent confirmed multiple beta-cell antibodies. Primary outcome can develop any time up to last study visit at 7.5 yrs). 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?

On the ClinicalTrials.gov record for NCT03364868, which also lists 3 linked publications.

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 8 Oct 2024.

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