Primary Intervention With Mucosal Insulin

Phase 1

Completed

• Conditions: Type 1 Diabetes
• Interventions: Drug: Human Insulin; Other: Oral Placebo

• Registration Number: NCT02620553
• Lead Sponsor: University of Colorado, Denver

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.

Study Timeline

• Study Start: 2007-09
• Primary Completion: 2013-06
• Study Completion: 2014-01
• Study First Submitted: 2015-06-08
• Study First Submitted QC: 2015-11-30
• Study First Posted: 2015-12-03
• Disposition First Submitted: 2015-12-18
• Status Verified: 2017-04
• Disposition First Submitted QC: 2017-04-19
• Last Update Submitted: 2017-04-19
• Disposition First Posted: 2017-04-20
• Last Update Posted: 2017-04-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Human Insulin	Human Insulin	Oral Insulin at 2.5 mg, 7.5 mg, 22.5 mg, or 67.5 mg per day
Placebo	Oral Placebo	Oral Placebo

Primary Outcome Measures

Name	Time	Method
Daily Evaluation of Blood Glucose Levels	Days 2 through 7	Blood glucose will be measured 60 minutes after the administration of the Insulin.
Change in Blood Glucose Levels	Day 1	Evaluation for hypoglycemia will be measured prior to administration of the insulin (baseline), then at 30, 60, and 120 minutes after administration of the insulin.
Evaluation of Blood Glucose Levels	Measured 60 minutes after oral insulin dosing, every day during each 4th week, as long as the subject is given oral insulin.	After treatment day 7, Insulin will be administered and measured on a monthly basis.

Secondary Outcome Measures

Name	Time	Method
Change in Total IgE and IgE.	2 weeks, 3 months, 6 months	Allergy/intolerance to the study drug evaluated with total IgE and IgE antibodies to insulin at 2 weeks, 3 months, 6 months, then every 6 months thereafter, as well as monitored through self-reporting by families. Parents/guardians will be educated on and instructed to look out for possible allergic reactions to insulin.
T-cell responses related to potential immune response to Insulin	Day 1, 15 days, 3 and 6 months.	T-cell responses e.g. antibody and cell mediated immune results will be evaluated the day of administration then at 15 days, 3 and 6 months, and every 6 months of treatment, and will be reported directly to the Data Coordinating Center.

Trial Locations

Locations (1)

Barbara Davis Center for Childhood Diabetes; 🇺🇸 Aurora, Colorado, United States