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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: February 6, 2017
Last verified: February 2017
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: Rapamycin
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
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 ]

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

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: 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 Name: 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:
  • Rapamune
  • Sirolimus

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   (Adult)
Sexes Eligible for Study:   All
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;
  • 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.
  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:
Study Data/Documents: Individual Participant Data Set  This link exits the site
Identifier: SDY565
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.
Study protocol summary and -schematic, -design, -demographics, -lab tests, -mechanistic assays, and -files  This link exits the site
Identifier: SDY565
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.

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: February 6, 2017
Individual Participant Data  
Plan to Share IPD: Yes
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.

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, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents processed this record on May 24, 2017