Primary Intervention With Mucosal Insulin

NCT ID: NCT02620553

Last Updated: 2017-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2014-01-31

Brief Summary

A dose with proven drug bioavailability to the immune system for use in a phase II/III primary T1DM (type 1 diabetes) vaccination trial (POINT study) in genetically at risk subjects.

Study Design Randomized, placebo-controlled, double-blind/double-masked, multi-center, dose escalation primary intervention pilot study.

Accrual Objective 25 (3:2 randomization to active and control arms)

Detailed Description

The objective of this study is to determine the feasibility, safety and bioavailability of oral insulin in children with high genetic risk for T1DM in a dose escalation primary intervention pilot study.

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Human Insulin

Oral Insulin at 2.5 mg, 7.5 mg, 22.5 mg, or 67.5 mg per day

Group Type: EXPERIMENTAL

Human Insulin

Intervention Type: DRUG

There is a study drug dose increase once during the study. The dose increase will occur 6 months after entering into the study. A total of 6 children will be included at each dose (3 children will not have received insulin prior to entering the study and 3 children will have received a lower dose of insulin for 6 months). Further dose increases or more frequent dose increases in individual children will not be performed during Pre-POINT. Escalation will occur in both treatment and placebo group so that participants and study investigators will remain blinded to treatment throughout the study. First dose (2.5 mg oral insulin/day) Second dose (7.5 mg oral insulin/day) Third dose (22.5 mg oral insulin/day) Fourth dose (67.5 mg oral insulin/day)

Placebo

Oral Placebo

Group Type: PLACEBO_COMPARATOR

Oral Placebo

Intervention Type: OTHER

Oral Placebo is given orally daily

Interventions

Human Insulin

There is a study drug dose increase once during the study. The dose increase will occur 6 months after entering into the study. A total of 6 children will be included at each dose (3 children will not have received insulin prior to entering the study and 3 children will have received a lower dose of insulin for 6 months). Further dose increases or more frequent dose increases in individual children will not be performed during Pre-POINT. Escalation will occur in both treatment and placebo group so that participants and study investigators will remain blinded to treatment throughout the study. First dose (2.5 mg oral insulin/day) Second dose (7.5 mg oral insulin/day) Third dose (22.5 mg oral insulin/day) Fourth dose (67.5 mg oral insulin/day)

Intervention Type: DRUG

Oral Placebo

Oral Placebo is given orally daily

Intervention Type: OTHER

Other Intervention Names

Oral Insulin

Eligibility Criteria

Inclusion Criteria

1. Children aged 2 years to 7 years who:

• Have a multiplex first degree family history of T1DM (both parents, parent and sib, or two sibs);
• Type 1 diabetes susceptible HLA DR4-DQB1*0302 or DR4-DQB1*0304 haplotype and

None of the following HLA DR or DQB1 alleles:

• DR 11
• DR 12
• DQB1*0602
• DR7-DQB1*0303
• DR14-DQB1*0503 or
• Have a sibling with T1DM;
• Identical by descent for the HLA DR3/DR4-DQ8 genotype with their diabetic sibling;

2. Islet autoantibody negative at time of recruitment.

Exclusion Criteria

1. Children with any kind of congenital or acquired chronic disease that potentially interfere with the study objectives.

2. Prior or current participation in another intervention trial.

3. Chronic oral steroid use and/or other chronic oral immunosuppressant

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 7 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital Dresden

OTHER

Sponsor Role: collaborator

Diabetes Research Institute, Munich, Germany.

UNKNOWN

Sponsor Role: collaborator

University of Bristol

OTHER

Sponsor Role: collaborator

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role: collaborator

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ezio Bonifacio, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical Faculty Carl Gustav Carus, Dresden University of Technology

Georgeanna J Klingensmith, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

Barbara Davis Center for Childhood Diabetes

Aurora, Colorado, United States

Countries

United States

References

Bonifacio E, Ziegler AG, Klingensmith G, Schober E, Bingley PJ, Rottenkolber M, Theil A, Eugster A, Puff R, Peplow C, Buettner F, Lange K, Hasford J, Achenbach P; Pre-POINT Study Group. Effects of high-dose oral insulin on immune responses in children at high risk for type 1 diabetes: the Pre-POINT randomized clinical trial. JAMA. 2015 Apr 21;313(15):1541-9. doi: 10.1001/jama.2015.2928.

Reference Type: RESULT

PMID: 25898052 (View on PubMed)

Other Identifiers

05-1043

Identifier Type: -

Identifier Source: org_study_id