Proleukin and Rapamune in Type 1 Diabetes

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00525889
• Other study ID #: DAIT ITN018AI
• Status: Completed
• Phase: Phase 1
• First received: September 4, 2007
• Last updated: February 6, 2017
• Start date: August 2007
• Est. completion date: September 2013

Study information

• Verified date: February 2017
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: September 2013
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Naomi Berrie Diabetes Center, Columbia University	New York	New York
United States	Oregon Health Sciences University	Portland	Oregon
United States	Benaroya Research Institute	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Immune Tolerance Network (ITN)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Long SA, Rieck M, Sanda S, Bollyky JB, Samuels PL, Goland R, Ahmann A, Rabinovitch A, Aggarwal S, Phippard D, Turka LA, Ehlers MR, Bianchine PJ, Boyle KD, Adah SA, Bluestone JA, Buckner JH, Greenbaum CJ; Diabetes TrialNet and the Immune Tolerance Network. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of adverse events and laboratory anomalies		through day 364
Secondary	AUC for C-peptide responses following MMTT		various
Secondary	Frequency of severe hypoglycemia		various
Secondary	Insulin dose in units per kilogram		various
Secondary	HbA1c levels		various

External Links

•   Division of Allergy, Immunology, and Transplantation (DAIT) website
•   Immune Tolerance Network (ITN) website
•   National Institute of Allergy and Infectious Diseases (NIAID) website