ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03364868
Recruitment Status : Recruiting
First Posted : December 7, 2017
Last Update Posted : July 3, 2018
Sponsor:
Collaborators:
The Leona M. and Harry B. Helmsley Charitable Trust
Helmholtz Zentrum München
University Hospital Carl Gustav Carus
Kinderkrankenhaus auf der Bult
Skane University Hospital
Universitaire Ziekenhuizen Leuven
Medical University of Warsaw
University of Oxford, Clinical Vaccine Research and Immunisation Education
Information provided by (Responsible Party):
Technische Universität München

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: Oral Insulin Other: Placebo Phase 2

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 currently ongoing 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1040 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Oral Insulin Therapy for Prevention of Autoimmune Diabetes
Actual Study Start Date : February 7, 2018
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : January 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: oral insulin capsule (dose escalation using 3 dose strengths)
Dose 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.
Drug: Oral Insulin
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.

Placebo Comparator: Placebo capsule
Daily treatment with placebo capsules containing filling substance (microcrystalline cellulose).
Other: Placebo
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).




Primary Outcome Measures :
  1. 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 ]
    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.

  2. The development of diabetes [ Time Frame: 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 ]
    OGTT criteria or clinical criteria for diabetes as defined by the American Diabetes Association (ADA).


Secondary Outcome Measures :
  1. Any persistent confirmed beta-cell autoantibody or diabetes [ Time Frame: 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 ]
    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).

  2. Persistent confirmed IAA. [ Time Frame: 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. ]
    Confirmed IAA in two consecutive samples.

  3. Persistent confirmed GADA. [ Time Frame: 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 ]
    Confirmed GADA in two consecutive samples.

  4. Abnormal glucose tolerance (AGT) defined by dysglycemia or diabetes. [ Time Frame: 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 ]
    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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   4 Months to 7 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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:

  1. 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.
  2. 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.
  3. Solid foods introduced into diet of infant
  4. Written informed consent signed by the custodial parent(s).

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03364868


Contacts
Contact: Anette-G. Ziegler, Prof. Dr. +49-(0)800 - 000 00 18 contact@gppad.org
Contact: Peter Achenbach, PD Dr. +49-(0)800 - 000 00 18 contact@gppad.org

Locations
Belgium
University Hospitals Leuven, Faculty of Medicine, Catholic University of Leuven, Leuven, Belgium Not yet recruiting
Leuven, Belgium, 3000
Contact: Kristina Casteels, Prof. Dr.         
Germany
Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany Recruiting
Munich, Bavaria, Germany, 80804
Contact: Anette-G. Ziegler, Prof. Dr.    +49-(0)800 - 000 00 18    contact@gppad.org   
Contact: Peter Achenbach, Prof. Dr.    +49-(0)800 - 000 00 18    contact@gppad.org   
AUF DER BULT, Kinder- und Jugendkrankenhaus, Hanover, Germany Recruiting
Hanover, Lower Saxony, Germany, 30173
Contact: Olga Kordonouri, Prof. Dr.         
Klinik und Poliklinik f. Kinder und Jugendmedizin, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, CRTD/DFG-Forschungszentrum für Regenerative Therapien, Dresden, Germany Recruiting
Dresden, Saxony, Germany, 01307
Contact: Reinhard Berner, Prof. Dr.         
Poland
Medical University of Warsaw, Department of Paediatrics, Warsaw, Poland Active, not recruiting
Warsaw, Poland, 00-001
Sweden
Lund University Dep. of Clinical Sciences Malmo, Skane University Hospital SUS, University Hospital MAS, Malmo, Sweden Not yet recruiting
Malmö, Sweden, 202 13
Contact: Helena Elding Larsson, Assoc. Prof. Dr.         
United Kingdom
Department of Paediatrics Clinical Vaccine Research and Immunisation Education, Children's Hospital, Headington, Oxford, UK Not yet recruiting
Oxford, United Kingdom, OX3 9DU
Contact: Matthew Snape, Dr.         
Sponsors and Collaborators
Technische Universität München
The Leona M. and Harry B. Helmsley Charitable Trust
Helmholtz Zentrum München
University Hospital Carl Gustav Carus
Kinderkrankenhaus auf der Bult
Skane University Hospital
Universitaire Ziekenhuizen Leuven
Medical University of Warsaw
University of Oxford, Clinical Vaccine Research and Immunisation Education

Additional Information:
Responsible Party: Technische Universität München
ClinicalTrials.gov Identifier: NCT03364868     History of Changes
Other Study ID Numbers: GPPAD-03-POInT
First Posted: December 7, 2017    Key Record Dates
Last Update Posted: July 3, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Technische Universität München:
Type 1 diabetes
diabetes mellitus
at risk for developing type 1 diabetes
juvenile diabetes
autoimmune diabetes
T1D
oral insulin
oral tolerance
autoantigen
self tolerance
prevention

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs