PEDIATRIC DIABETES RESEARCH CENTER

Type 1 Studies

Recruitment Contact:
Marla Hashiguchi, RN
Phone: (858) 966-8940
mhashiguchi@rchsd.org

ALPHA-1 ANTITRYPSIN (RETAIN) STUDY IS ON HOLD AT THIS TIME.

Purpose

PRIMARY OBJECTIVE

  1. 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.

SECONDARY OBJECTIVES

Diabetes related:

  1. Assess whether Aralast NP has prolonged clinical efficacy.
  2. Assess the effect of Aralast NP on selected secondary clinical outcomes.

Safety and pharmacokinetic:

  1. Determine the PK of Aralast NP in a cohort of participants with T1DM.
  2. Determine the safety of Aralast NP in participants with T1DM, especially with respect to hypersensitivity.

EXPLORATORY OBJECTIVES

Mechanistic:

  1. 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.
  2. Development of a pharmacokinetic/pharmacodynamic (PK/PD) model.

Metabolic:

  1. Determine whether treatment with Aralast NP improves glycemic control and reduces individual requirements.

Eligibility

Inclusion Criteria:

  1. 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.
  2. Diagnosis of T1DM within 100 days of Visit 0.
  3. Positive for at least one diabetes-related autoantibody:

    1. Anti-GAD;
    2. Anti-insulin, if obtained within 10 days of the onset of insulin therapy;
    3. IA-2 antibody and/or ICA, or ZnT8.
  4. Peak stimulated C-peptide level > 0.2 pmol/mL following an MMTT.

  5. Signed informed consent.

Exclusion Criteria:

  1. 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.
  2. History of any bleeding tendency including essential thrombocythemia or clotting factor deficiencies, or prior history of stroke or other thromboembolic event.
  3. History of vascular disease or significant vascular abnormalities (not including benign murmurs, mitral valve prolapse, or cutaneous vascular malformations).
  4. Positive serology of exposure to HBV (HBsAg), HCV, HIV or toxoplasmosis.
  5. 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.
  6. 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.
  7. Current or prior (within the last 30 days) use of metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin.
  8. Current use of any medication known to influence glucose tolerance (e.g., atypical antipsychotics, diphenylhydantoin, thiazide or other potassium-depleting diuretics, ßadrenergic blockers, niacin).
  9. Any of the following as confirmed in a repeat test at least 1 week apart:

    1. Leukopenia (WBC < 3.0 ´ 103/μL)
    2. Anemia (Hgb < 10.0 g/dL).
    3. Thrombocytopenia (platelets < 100 ´ 103/μL).
    4. Impaired kidney function (serum creatinine > 1.5 mg/dL).
    5. Impaired liver function (ALT or AST > 2.0 times ULN).
    6. Plasma D-dimer level > assay-specific cut-off value
    7. Positive anti-cardiolipin antibody.
  10. Females who are pregnant or lactating, or are unwilling to defer pregnancy during study participation.

  11. IgA deficiency (<7 mg/dL).
  12. Prior treatment with AAT or hypersensitivity to AAT or human plasma-derived products.
  13. 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.
  14. Current life-threatening malignancy.
  15. 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:

  1. To characterize their risk for developing T1D
  2. To describe the pathogenetic evolution of T1D, and
  3. To increase the understanding of the pathogenetic factors involved in the development of T1D.

Within this overall objective, the specific objectives are:

  1. 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.
  2. To examine the accuracy of TrialNet risk assessment procedures for predicting future T1D.
  3. To determine the prevalence of impaired glucose tolerance and ICA positivity in individuals with at least one positive biochemical autoantibody test.
  4. To characterize the progression of immunologic abnormalities in the development of T1D by serially studying biochemical autoantibodies, ICA, and markers of cell-mediated immunity.
  5. 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.
  6. 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.
  7. To identify individuals who qualify for TrialNet prevention trials for T1D.
  8. 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.
  9. To accrue additional information about genetic markers associated with risk for the development of T1D by analyzing stored blood samples.
  10. 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.