Clinical trial NCT00468442 (phase 2, status: terminated)
Conditions: type 1 diabetes mellitus
ICD codes: E10.65, E10.9, E10.21, E10.36, E10.41, E10.42, E10.44
Drugs: sirolimus
SMILES: CC(=O)CC(C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2
Reason stopped: 
    lack of efficacy
  
Eligibility criteria:

        Inclusion Criteria:

          -  Mentally stable and able to comply with study procedures

          -  Clinical history compatible with type 1 diabetes with onset at less than 40 years of
             age, insulin dependence for at least 5 years at study entry, and a sum of age and
             insulin dependent diabetes duration of at least 28

          -  Absent stimulated C-peptide (less than 0.3 ng/ml) 60 and 90 minutes post-mixed-meal
             tolerance test

          -  Involvement of intensive diabetes management, defined as:

               1. Self-monitoring of glucose values no less than a mean of three times each day
                  averaged over each week

               2. Administration of three or more insulin injections each day or insulin pump
                  therapy

          -  Under the direction of an endocrinologist, diabetologist, or diabetes specialist with
             at least three evaluations the 12 months prior to study enrollment

          -  At least one episode of severe hypoglycemia in the past 12 months, defined as an event
             with one of the following symptoms: memory loss; confusion; uncontrollable behavior;
             irrational behavior; unusual difficulty in awakening; suspected seizure; seizure; loss
             of consciousness; or visual symptoms in which the participant was unable to treat
             him/herself and which was associated with either a blood glucose (BG) level < 54 mg/dL
             [3.0 mmol/L] or prompt recovery after oral carbohydrate, intravenous glucose, or
             glucagon administration, in the past 12 months prior to study enrollment

          -  Reduced awareness of hypoglycemia. More information about this criterion, including
             specific definition of hypoglycemia unawareness, is in the protocol.

        Exclusion Criteria:

          -  Body mass index (BMI) greater than 30 kg/m2 or weight less than or equal to 50 kg

          -  Insulin requirement of more than 1.0 IU/kg/day or less than 15 U/day

          -  HbA1c greater than 10%

          -  Untreated proliferative diabetic retinopathy

          -  Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than
             100 mmHg

          -  Measured glomerular filtration rate using iohexol of less than 80 ml/min/1.73m2. More
             information about this criterion is in the protocol.

          -  Presence or history of macroalbuminuria (greater than 300 mg/g creatinine)

          -  Presence or history of panel-reactive anti-HLA antibody levels greater than 20% by
             flow cytometry. More information about this criterion is in the protocol.

          -  Pregnant, breastfeeding, or unwilling to use effective contraception throughout the
             study and 4 months after study completion

          -  Active infection, including hepatitis B, hepatitis C, HIV, or tuberculosis. More
             information about this criterion is in the protocol.

          -  Negative for Epstein-Barr virus by IgG determination

          -  Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection within one year
             prior to study enrollment

          -  History of malignancy except for completely resected squamous or basal cell carcinoma
             of the skin

          -  Known active alcohol or substance abuse

          -  Baseline Hgb below the lower limits of normal, lymphopenia, neutropenia, or
             thrombocytopenia

          -  History of Factor V deficiency

          -  Any coagulopathy or medical condition requiring long-term anticoagulant therapy after
             transplantation or individuals with an INR greater than 1.5

          -  Severe coexisting cardiac disease, characterized by any one of the following
             conditions:

               1. Heart attack within the last 6 months

               2. Evidence of ischemia on functional heart exam within the year prior to study
                  entry

               3. Left ventricular ejection fraction less than 30%

          -  Persistent elevation of liver function tests at the time of study entry

          -  Symptomatic cholecystolithiasis

          -  Acute or chronic pancreatitis

          -  Symptomatic peptic ulcer disease

          -  Severe unremitting diarrhea, vomiting, or other gastrointestinal disorders that could
             interfere with the ability to absorb oral medications

          -  Hyperlipidemia despite medical therapy (fasting LDL cholesterol greater than 130
             mg/dl, treated or untreated; and/or fasting triglycerides greater than 200 mg/dl)

          -  Receiving treatment for a medical condition that requires chronic use of systemic
             steroids, except the use of 5 mg or less of prednisone daily, or an equivalent dose of
             hydrocortisone, for physiological replacement only

          -  Treatment with antidiabetic medication other than insulin within the past 4 weeks

          -  Use of any investigational agents within the past 4 weeks

          -  Received a live attenuated vaccine(s) within 2 months of study entry

          -  Any medical condition that, in the opinion of the investigator, will interfere with
             safe participation in the trial

          -  Treatment with any immunosuppressive regimen at the time of enrollment

          -  A previous islet transplant

          -  A previous pancreas transplant, unless the graft failed within the first week due to
             thrombosis, followed by pancreatectomy and transplant occurred more than 6 months
             prior to enrollment