Novel Therapy to Preserve Beta Cell Function in New Onset Type 1 Diabetes
Condition: Diabetes Mellitus Type 1; Autoimmune Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Insulin; Lansoprazole; Sitagliptin; Diamyd; GAD65 (Diamyd)
Intervention MeSH terms: Sitagliptin Phosphate; Lansoprazole; Dexlansoprazole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 16 Years
Maximum age: 30 Years
Healthy volunteers: No
Keywords: Type I Diabetes; Preserve Beta Cell Function; Sitagliptin; Lansoprazole; GAD65 (Diamyd); Diabetes; Type 1 Diabetes; T1DM

Summary:

      Background:

        -  Type 1 diabetes (T1D) occurs when the immune system attacks insulin-producing cells
           (beta cells) in the pancreas, resulting in their death.

        -  Insulin injections currently are the best method for controlling blood sugar in
           individuals with T1D. However, animal studies have shown that the drugs sitagliptin and
           lansoprazole can help reverse beta cell damage or develop new beta cells. In addition,
           Diamyd has been shown to weaken the immune process that attacks pancreatic beta cells.

      Objectives:

        -  To find out whether a combination treatment of sitagliptin, lansoprazole, and Diamyd
           will help maintain functioning beta cells and/or cause new beta cells to form.

        -  To determine how the drug combination affects insulin doses and blood sugar control.

        -  To determine whether the drug combination affects the immune response involved in T1D.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Recently diagnosed (within the preceding 4 months of screening) diabetes
                  clinically consistent with T1D:

                  A. Positive for anti-GAD antibody.

                  B. BMI between 19 and 28 kg/m2; for those between the ages of 16 to 18, the BMI
                  must be within 10th to 90th percentile for the age.

               2. Ages between 16 and 30 years, inclusive

               3. Random plasma C-peptide level of equal to or greater than 0.20 nmol/L

               4. Willingness and ability to institute intensive insulin-based glucose management.

        EXCLUSION CRITERIA:

          1. Diabetic nephropathy with a creatinine clearance less than 60 cc/min or 24 hour urine
             albumin greater than 300 mg

          2. Insulin requirements greater than 0.8 units/kg/day at the end of the run-in period

          3. Regular use of a proton pump inhibitor within 3 months of enrollment

          4. Use of GLP-1R agonist or DPP-4 inhibitor within 6 months prior to enrollment

          5. Use of immunosuppressive therapy in the preceding 12 months

          6. Evidence of chronic infection, for example, known human immunodeficiency virus (HIV)
             or hepatitis

          7. History of any malignancy other than a treated basal or squamous skin cancer

          8. Any chronic medical condition to unduly increase risk for the potential enrollee as
             judged by study investigators

          9. Pregnancy, breastfeeding or planned pregnancy within two years, women of reproductive
             age not using an effective mode of contraception and unwilling to continue adequate
             contraception until 1 year after the last study drug administration

         10. Any other co-existing condition/circumstances that would make patient unsuitable to
             participate in the study, as deemed by the investigators. For example, study
             investigators would exclude any potential candidate with any of the following (but the
             list is not inclusive):

        A. Clinically significant past history of an acute reaction to vaccines or other drugs

        B. Recent participation in other clinical trials with a new chemical entity

        C. A history of alcohol or drug abuse

        D. Significant neurological conditions like epilepsy, head trauma, or cerebrovascular
        accidents

        E. Individuals with significant gastrointestinal disorders determined by the study
        investigators to influence either study safety or data interpretation. Such conditions
        include but are not limited to gastroparesis and gastric bypass surgery

        F. Individuals with conditions prone to hypergastrinemia (Zollinger-Ellison syndrome, use
        of histamine-2 receptor blockers) or hypogastrinemia (gastric surgery).