Proleukin and Rapamune in Type 1 Diabetes - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	Immune Tolerance Network (ITN)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00525889

Purpose

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 I

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

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Medicines Diabetes Type 1

Drug Information available for: Sirolimus Aldesleukin Everolimus CCI 779

U.S. FDA Resources

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 ]

Estimated Enrollment:	10
Study Start Date:	August 2007
Estimated Study Completion Date:	September 2013
Estimated 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.

Eligibility

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

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00525889

Locations

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)

Investigators

Principal Investigator:

Carla Greenbaum, MD

Benaroya Research Institute

More Information

Additional Information:

Immune Tolerance Network This link exits the ClinicalTrials.gov site

Clinical Trials at Benaroya Research Institute This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Associate Director, Clinical Research Program, DAIT/NIAID
ClinicalTrials.gov Identifier:	NCT00525889 History of Changes
Other Study ID Numbers:	DAIT ITN018AI
Study First Received:	September 4, 2007
Last Updated:	December 20, 2010
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

diabetes
juvenile diabetes
type 1 diabetes

diabetes mellitus
recent onset
new onset

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Sirolimus
Everolimus
Aldesleukin
Antibiotics, Antineoplastic
Antineoplastic Agents

Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents

ClinicalTrials.gov processed this record on February 12, 2012