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Primary Intervention With Mucosal Insulin (Pre-POINT)

Primary Purpose

Type 1 Diabetes

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Human Insulin
Oral Placebo
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Type 1 Diabetes focused on measuring Type 1 Diabetes, Diabetes, Autoimmune Diabetes

Eligibility Criteria

2 Years - 7 Years (Child)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Barbara Davis Center for Childhood Diabetes

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Human Insulin

Placebo

Arm Description

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

Oral Placebo

Outcomes

Primary Outcome Measures

Change in Blood Glucose Levels
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.
Daily Evaluation of Blood Glucose Levels
Blood glucose will be measured 60 minutes after the administration of the Insulin.
Evaluation of Blood Glucose Levels
After treatment day 7, Insulin will be administered and measured on a monthly basis.

Secondary Outcome Measures

Change in Total IgE and IgE.
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
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.

Full Information

First Posted
June 8, 2015
Last Updated
April 19, 2017
Sponsor
University of Colorado, Denver
Collaborators
University Hospital Dresden, Diabetes Research Institute, Munich, Germany., University of Bristol, Juvenile Diabetes Research Foundation, German Federal Ministry of Education and Research
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1. Study Identification

Unique Protocol Identification Number
NCT02620553
Brief Title
Primary Intervention With Mucosal Insulin
Acronym
Pre-POINT
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

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
University Hospital Dresden, Diabetes Research Institute, Munich, Germany., University of Bristol, Juvenile Diabetes Research Foundation, German Federal Ministry of Education and Research

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
Type 1 Diabetes, Diabetes, Autoimmune Diabetes

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Human Insulin
Arm Type
Experimental
Arm Description
Oral Insulin at 2.5 mg, 7.5 mg, 22.5 mg, or 67.5 mg per day
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Oral Placebo
Intervention Type
Drug
Intervention Name(s)
Human Insulin
Other Intervention Name(s)
Oral Insulin
Intervention Description
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
Other
Intervention Name(s)
Oral Placebo
Intervention Description
Oral Placebo is given orally daily
Primary Outcome Measure Information:
Title
Change in Blood Glucose Levels
Description
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.
Time Frame
Day 1
Title
Daily Evaluation of Blood Glucose Levels
Description
Blood glucose will be measured 60 minutes after the administration of the Insulin.
Time Frame
Days 2 through 7
Title
Evaluation of Blood Glucose Levels
Description
After treatment day 7, Insulin will be administered and measured on a monthly basis.
Time Frame
Measured 60 minutes after oral insulin dosing, every day during each 4th week, as long as the subject is given oral insulin.
Secondary Outcome Measure Information:
Title
Change in Total IgE and IgE.
Description
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.
Time Frame
2 weeks, 3 months, 6 months
Title
T-cell responses related to potential immune response to Insulin
Description
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.
Time Frame
Day 1, 15 days, 3 and 6 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
7 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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; Islet autoantibody negative at time of recruitment. Exclusion Criteria: Children with any kind of congenital or acquired chronic disease that potentially interfere with the study objectives. Prior or current participation in another intervention trial. Chronic oral steroid use and/or other chronic oral immunosuppressant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ezio Bonifacio, PhD
Organizational Affiliation
Medical Faculty Carl Gustav Carus, Dresden University of Technology
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Georgeanna J Klingensmith, MD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
Barbara Davis Center for Childhood Diabetes
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
25898052
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.
Results Reference
result

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Primary Intervention With Mucosal Insulin

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