Clinical trial NCT02620553: Primary Intervention With Mucosal Insulin
Official title: Primary Intervention With Mucosal Insulin for Prevention of Type 1 Diabetes in Infants at High Genetic Risk to Develop Diabetes POINT (Primary Oral Insulin Trial) A Dose Finding and Safety Study ( Pre-POINT )
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Type 1 Diabetes
Keywords: Type 1 Diabetes
Diabetes
Autoimmune Diabetes
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: University Hospital Dresden
name: Diabetes Research Institute, Munich, Germany.
name: University of Bristol
name: Juvenile Diabetes Research Foundation
name: German Federal Ministry of Education and Research
First posted: 2015-12-03
Enrollment: 25
Sex: ALL
Minimum age (years): 2
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Change in Blood Glucose Levels
timeFrame: Day 1
measure: Daily Evaluation of Blood Glucose Levels
timeFrame: Days 2 through 7
measure: Evaluation of Blood Glucose Levels
timeFrame: Measured 60 minutes after oral insulin dosing, every day during each 4th week, as long as the subject is given oral insulin.
Secondary outcomes:
measure: Change in Total IgE and IgE.
timeFrame: 2 weeks, 3 months, 6 months
measure: T-cell responses related to potential immune response to Insulin
timeFrame: Day 1, 15 days, 3 and 6 months.
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Barbara Davis Center for Childhood Diabetes
state: Colorado
Study officials:
affiliation: Medical Faculty Carl Gustav Carus, Dresden University of Technology
name: Ezio Bonifacio, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Georgeanna J Klingensmith, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.