Proleukin and Rapamune in Type 1 Diabetes

February 6, 2017 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Phase I Trial of Proleukin and Rapamune in Recent-onset Type 1 Diabetes Mellitus (ITN018AI)

This is a phase I trial in individuals who have been diagnosed with type 1 diabetes within the previous 3-48 months. The study is testing whether two immune system modifying drugs are safe when used in combination and if they have immune altering effects that indicate they can halt the progression of type 1 diabetes progression.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

At the time of diagnosis with type 1 diabetes, 15-40% of beta cells may remain active and healthy in the pancreas, capable of producing insulin the body needs to regulate blood glucose levels. Because even small amounts of natural insulin production can decrease the long term effects of diabetes, it is essential that these cells are preserved.

This trial will test whether a combination of the drugs Proleukin (IL-2) and Rapamune (sirolimus) may be safely administered to recently diagnosed type 1 diabetes patients and whether it causes changes to the immune system that can halt the autoimmune destruction of the remaining beta cells. This drug combination has been found to be effective for long-term diabetes prevention in mouse models of type 1 diabetes.

This study is a phase I study for individuals 18-45 years of age who have been diagnosed with type 1 diabetes in the past 3-48 months. All participants will be treated with Proleukin (administered subcutaneously 3x per week) for 28 days and Rapamune (taken orally, daily) for 12 weeks. The study will last for 12 months, with additional follow-up of 24 months. The majority of study visits occur within the first 6 months. Mixed meal tolerance tests, in which participants take a milkshake-like drink and have blood sampled over a 2 or 4-hour period, will take place during an initial screening visit and three additional times during the first year. All participants will also receive intensive diabetes management designed to maintain stable blood glucose levels.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • Naomi Berrie Diabetes Center, Columbia University
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health Sciences University
    • Washington
      • Seattle, Washington, United States, 98101
        • Benaroya Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosed with type 1 diabetes (per ADA criteria) more than 3 but less than 48 months prior to enrollment;
  • 18 to 45 years of age;and
  • Positive for at least one islet cell autoantibody (GAD65-antibody, CA512-antibody and/or ICA).

Exclusion Criteria:

  • Chronic use of glucocorticoids or other immunosuppressive ages 4 weeks before enrollment;
  • History of recurrent infections, other autoimmune diseases, cardiac disease, cataracts or other chronic medical conditions that investigators believe could compromise participant safety;
  • Females who are pregnant, lactating intend to get pregnant, or are unwilling to undergo pregnancy testing during the study;
  • Males who intend to father a pregnancy during the first 6 months of the study; or
  • Participation in another clinical study within the last 30 days.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rapamycin/IL-2 combination therapy
IL-2 (Proleukin) was administered at 4.5 3 106 IU s.c., three times per week for 4 weeks for a total of 12 doses. Rapamycin (Rapamune or Sirolimus) was administered without a loading dose at 2 mg/day, with adjustments to maintain trough blood levels of 5-10 ng/mL for 3 months.
Drug: IL-2
Administered by subcutaneous injection at a dose of 4.5x10^6 IU/day, three times weekly for 28 days starting on day 0.
Other Names:
  • Proleukin
Drug: Rapamycin
Administered orally, initial daily dose of 2mg. At day 7, dose adjusted to achieve and maintain whole blood trough levels of 5-10 ng/ml.
Other Names:
  • Sirolimus
  • Rapamune

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence and severity of adverse events and laboratory anomalies
Time Frame: through day 364
through day 364

Secondary Outcome Measures

Outcome Measure
Time Frame
AUC for C-peptide responses following MMTT
Time Frame: various
various
Frequency of severe hypoglycemia
Time Frame: various
various
Insulin dose in units per kilogram
Time Frame: various
various
HbA1c levels
Time Frame: various
various

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Immune Tolerance Network (ITN)

Investigators

  • Principal Investigator: Carla Greenbaum, MD, Benaroya Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Primary Completion (Actual)

September 1, 2011

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

September 4, 2007

First Submitted That Met QC Criteria

September 5, 2007

First Posted (Estimate)

September 6, 2007

Study Record Updates

Last Update Posted (Estimate)

February 8, 2017

Last Update Submitted That Met QC Criteria

February 6, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAIT ITN018AI

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Participant level data and additional relevant materials are available to the public in the Immunology Database and Analysis Portal (ImmPort). ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: SDY565
    Information comments: ImmPort study identifier is SDY565. ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts available to the Public.
  2. Study protocol summary and -schematic, -design, -demographics, -lab tests, -mechanistic assays, and -files
    Information identifier: SDY565
    Information comments: ImmPort study identifier is SDY565. ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts available to the Public.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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