Primary Intervention With Mucosal Insulin

NCT02620553 | Completed Phase 1 DMC

• 1 other identifier: 05-1043
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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)

Conditions

Type 1 Diabetes

Keywords

Type 1 Diabetes; Diabetes; Autoimmune Diabetes

Outcome Measures

Primary Outcomes (3)

• 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.

  Day 1

• Daily Evaluation of Blood Glucose Levels

  Blood glucose will be measured 60 minutes after the administration of the Insulin.

  Days 2 through 7

• Evaluation of Blood Glucose Levels

  After treatment day 7, Insulin will be administered and measured on a monthly basis.

  Measured 60 minutes after oral insulin dosing, every day during each 4th week, as long as the subject is given oral insulin.

Secondary Outcomes (2)

• Change in Total IgE and IgE.

  2 weeks, 3 months, 6 months

• T-cell responses related to potential immune response to Insulin

  Day 1, 15 days, 3 and 6 months.

Study Arms (2)

Human Insulin

EXPERIMENTAL

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

Drug: Human Insulin

Placebo

PLACEBO COMPARATOR

Oral Placebo

Other: Oral Placebo

Interventions

Human Insulin 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)

Also known as: Oral Insulin

Human Insulin

Oral Placebo OTHER

Oral Placebo is given orally daily

Placebo

Eligibility Criteria

• Age: 2 Years - 7 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• University Hospital Dresden: collaborator
• Diabetes Research Institute, Munich, Germany.: collaborator
• University of Bristol: collaborator
• Juvenile Diabetes Research Foundation: collaborator
• German Federal Ministry of Education and Research: collaborator

Study Sites (1)

Barbara Davis Center for Childhood Diabetes

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• 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.

  PMID: 25898052 RESULT

Related Links

• Pre-POINT

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Interventions

Insulin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Ezio Bonifacio, PhD

  Medical Faculty Carl Gustav Carus, Dresden University of Technology

  PRINCIPAL INVESTIGATOR

• Georgeanna J Klingensmith, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2015
• First Posted: December 3, 2015
• Study Start: September 1, 2007
• Primary Completion: June 1, 2013
• Study Completion: January 1, 2014
• Last Updated: April 20, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)