Type 1 Studies
Marla Hashiguchi, RN
Phone: (858) 966-8940
ALPHA-1 ANTITRYPSIN (RETAIN) STUDY IS ON HOLD AT THIS TIME.
- Determine whether Aralast NP will slow the progression of the autoimmune destruction of ß cells and lead to the preservation of C-peptide secretion in T1DM.
- Assess whether Aralast NP has prolonged clinical efficacy.
- Assess the effect of Aralast NP on selected secondary clinical outcomes.
Safety and pharmacokinetic:
- Determine the PK of Aralast NP in a cohort of participants with T1DM.
- Determine the safety of Aralast NP in participants with T1DM, especially with respect to hypersensitivity.
- Gain a better understanding of the mechanism of action for Aralast NP in the maintenance of ß-cell function and determine whether the loss of tolerance associated with this disease is reversed.
- Development of a pharmacokinetic/pharmacodynamic (PK/PD) model.
- Determine whether treatment with Aralast NP improves glycemic control and reduces individual requirements.
- Male or female aged 8–35 years who meets the American Diabetes Association standard T1DM criteria. Note: The first 8 participants in Part I will be 16–35 years of age.
- Diagnosis of T1DM within 100 days of Visit 0.
Positive for at least one diabetes-related autoantibody:
- Anti-insulin, if obtained within 10 days of the onset of insulin therapy;
- IA-2 antibody and/or ICA, or ZnT8.
Peak stimulated C-peptide level > 0.2 pmol/mL following an MMTT.
- Signed informed consent.
- Known severe active disease (e.g., chronic active hepatitis, severe cardiac, renal, hepatic, or pulmonary disease, immunodeficiency) and/or disease that is likely to limit life expectancy or lead to therapies such as immunosuppression during study participation.
- History of any bleeding tendency including essential thrombocythemia or clotting factor deficiencies, or prior history of stroke or other thromboembolic event.
- History of vascular disease or significant vascular abnormalities (not including benign murmurs, mitral valve prolapse, or cutaneous vascular malformations).
- Positive serology of exposure to HBV (HBsAg), HCV, HIV or toxoplasmosis.
- Clinically active infection with EBV, CMV, or tuberculosis, or EBV viral load ³ 10,000 copies per 106 PBMCs or CMV viral load ≥ 10,000 copies per mL whole blood.
- Prior or current treatment that is known to cause a significant, ongoing change in the course of T1DM or immunologic status, including high-dose inhaled, extensive topical or systemic glucocorticoids.
- Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin.
- Current use of any medication known to influence glucose tolerance (e.g., atypical antipsychotics, diphenylhydantoin, thiazide or other potassium-depleting diuretics, ßadrenergic blockers, niacin).
Any of the following as confirmed in a repeat test at least 1 week apart:
- Leukopenia (WBC < 3.0 ´ 103/μL)
- Anemia (Hgb < 10.0 g/dL).
- Thrombocytopenia (platelets < 100 ´ 103/μL).
- Impaired kidney function (serum creatinine > 1.5 mg/dL).
- Impaired liver function (ALT or AST > 2.0 times ULN).
- Plasma D-dimer level > assay-specific cut-off value
- Positive anti-cardiolipin antibody.
Females who are pregnant or lactating, or are unwilling to defer pregnancy during study participation.
- IgA deficiency (<7 mg/dL).
- Prior treatment with AAT or hypersensitivity to AAT or human plasma-derived products.
- Uncontrolled hypertension. In subjects 18 and older, this is defined as systolic ≥150 mm Hg, and/or diastolic ≥ 100 mmHg on 3 consecutive occasions in the supine position. In subjects <18 years of age, hypertension is defined as average SBP and/or DBP that is ≥ 95th percentile for gender, age and height on ≥3 occasions.
- Current life-threatening malignancy.
- Any condition that in the investigator’s opinion may compromise study participation or may confound the interpretation of the study results.
TRIALNET NATURAL HISTORY STUDY
Study population: 1st, 2nd and 3rd degree relatives of Type one diabetics, 1 to 45 years of age (1st degree relatives) and 1 to 20 year olds (2nd and 3rd degree relatives)
Inclusion/exclusion: The subjects cannot have diabetes (type 1 or type 2)
Study Aims: The overall objective of this study is to perform baseline and repeat assessments over time of the metabolic and immunologic status of individuals at risk for T1D in order:
- To characterize their risk for developing T1D
- To describe the pathogenetic evolution of T1D, and
- To increase the understanding of the pathogenetic factors involved in the development of T1D.
Within this overall objective, the specific objectives are:
- To determine the risk for the occurrence of T1D according to oral glucose tolerance tests (OGTT), C-peptide levels, biochemical autoantibodies (anti-GAD65, anti-ICA512 and IAA), islet cell autoantibodies (ICA), markers of cell-mediated immunity, and HLA genetic markers that are associated with risk for T1D.
- To examine the accuracy of TrialNet risk assessment procedures for predicting future T1D.
- To determine the prevalence of impaired glucose tolerance and ICA positivity in individuals with at least one positive biochemical autoantibody test.
- To characterize the progression of immunologic abnormalities in the development of T1D by serially studying biochemical autoantibodies, ICA, and markers of cell-mediated immunity.
- To characterize the progression of metabolic decompensation in the development of T1D by serially studying insulin, C-peptide and glucose levels, and to identify immunologic and other factors associated with this decompensation.
- To determine the incidence of severe acute metabolic decompensation as the initial clinical presentation in individuals who have been identified as being at increased risk for T1D.
- To identify individuals who qualify for TrialNet prevention trials for T1D.
- To accrue additional information about immunologic and metabolic factors related to the pathogenesis of T1D by analyzing stored blood samples. The Immune Tolerance Network will function as a core laboratory for TrialNet for the development of specialized immunologic procedures.
- To accrue additional information about genetic markers associated with risk for the development of T1D by analyzing stored blood samples.
- For those who participated in the DPT-1 study, to examine associations of characteristics (e.g. demographics, immunologic, metabolic, etc.) assessed during the DPT-1 study with characteristics and outcomes assessed in TrialNet.