Proleukin and Rapamune in Type 1 Diabetes

This study has been completed.
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID) Identifier:
First received: September 4, 2007
Last updated: March 25, 2014
Last verified: March 2014
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.

Condition Intervention Phase
Diabetes Mellitus, Type 1
Drug: IL-2
Drug: sirolimus
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Proleukin and Rapamune in Recent-onset Type 1 Diabetes Mellitus (ITN018AI)

Resource links provided by NLM:

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • incidence and severity of adverse events and laboratory anomalies [ Time Frame: through day 364 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • AUC for c-peptide responses following MMTT [ Time Frame: various ] [ Designated as safety issue: No ]
  • frequency of severe hypoglycemia [ Time Frame: various ] [ Designated as safety issue: Yes ]
  • insulin dose in units per kilogram [ Time Frame: various ] [ Designated as safety issue: No ]
  • HbA1c levels [ Time Frame: various ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: August 2007
Study Completion Date: September 2013
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: IL-2
administered by subcutaneous injection at a dose of 4.5x106 IU/day, three times weekly for 28 days starting on day 0
Other Name: Proleukin
Drug: sirolimus
administered orally, initial daily dose of 2mg PO. At day 7, dose adjusted to achieve and maintain whole blood trough levels of 5-10 ng/ml
Other Names:
  • Rapamune
  • Rapamycin

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.


Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosed with type 1 diabetes (per ADA criteria) more than 3 but less than 48 months prior to enrollment
  • Aged 18-45 years old
  • 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
  • participation in another clinical study within the last 30 days
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00525889

United States, New York
Naomi Berrie Diabetes Center, Columbia University
New York, New York, United States, 10032
United States, Oregon
Oregon Health Sciences University
Portland, Oregon, United States, 97239
United States, Washington
Benaroya Research Institute
Seattle, Washington, United States, 98101
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network (ITN)
Principal Investigator: Carla Greenbaum, MD Benaroya Research Institute
  More Information

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00525889     History of Changes
Other Study ID Numbers: DAIT ITN018AI 
Study First Received: September 4, 2007
Last Updated: March 25, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
juvenile diabetes
type 1 diabetes
diabetes mellitus
recent onset
new onset

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Anti-Bacterial Agents
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Physiological Effects of Drugs processed this record on May 26, 2016