Charles H. Best and Frederick Banting co-discovered insulin in 1921.

Perle Bioscience continues their efforts to help those living with diabetes.


Information for Healthcare Professionals

Type 1 diabetes is a serious, chronic disease affecting over 3 million children and adults in the United States alone.  Each day 80 children and adults are diagnosed with type 1 diabetes in the US.1  Type 1 diabetes affects every organ system of the body. The annual cost of medical care for young people with diabetes is six times higher than medical care for children and teens without the disease, according to the U.S. Centers for Disease Control and Prevention study.2  The cost of treating type 1 diabetes is estimated at $38,000 each year in the US for patients on insulin pumps.3  Type 1 diabetes accounts for $14.9 Billion in costs per year in the US.4,5

One of the greatest new insights in the field of type 1 diabetes is the understanding that unlike the success seen in type 1 mouse models treated with a variety of immune therapies, in man, beta cell regeneration does not occur.  Thus type 1 diabetes in man is now considered not only a disease of autoimmunity, but also a lack of beta cell regeneration, even in the presence of immune therapy. 6

The necessity of combination therapy with an immunosuppressant and a beta regeneration agent has evolved from the past 3 decades of type 1 diabetes research, in which two lines of research have dominated the field:  1) trials to alter the immunological response against beta cells, and 2) trials developing and replacing beta cells, including islet cell transplantation.  While immunosuppressants have been shown in some studies to prolong the maintenance of beta cells, it does not halt or reverse beta cell failure.  While beta cell replacement can result in insulin production, the effects are not long lasting.

Numerous different immunological based therapies have shown some ability to preserve remaining beta cell function, but none completely halted or reversed beta cell failure.  More than 50 trials have used a number of therapies among new onset type 1 patients including: the heat shock protein 60,  Diapep 277, Bacille Calmette–Guérin (BCG vaccine), mycophenolate mofetil, daclizumab, rituximab (anti CD20), anti CD3 antibodies including hOKT3 gamma1 (Ala-Ala), the monoclonal antibody TRX4 (ChAglyCD3), CTLA4-Ig (abatacept), campath-1H, the anti-CD52 antibody, a polyclonal anti-T-lymphocyte globulin (ATG), the GAD antibody vaccine based on the 65 kDa isoform of the recombinant human glutamic acid decarboxylase protein (rhGAD65), diazoxide, Alpha-1 Antitrypsin and others.

As a result of clinical trials to date, future clinical trials using a single immunosuppressant in new onset type 1 diabetes are no longer recommended by the Immune Tolerance Network and the Juvenile Diabetes Research Foundation.7   No single immunosuppressant, nor combination of immunosuppressants, has resulted in beta regeneration therapy in man.7,8

Therefore, new therapies that treat both autoimmunity and aid with beta cell regeneration may hold the key to future approaches for this significant public health concern with a large and growing unmet medical need. (Figure 1).6 To date, there have been no trials using a combination of both an immunosuppressant and a beta cell regeneration drug to preserve beta cell function in type 1 patients.

Figure 1: Combination therapy: Control Autoimmunity and Aid in Regeneration of Beta Cells

Research suggests that future therapies for type 1 diabetes may require an immune tolerance agent and a regeneration agent.

 

Combination-Therapy

Figure 2: Plasticity of adult human pancreatic ductal tissue.

The single larger black cell (left) represents the presence of Reg, and the pink cell is a progenitor cell within the ductal population. Blue cells indicate beta cells, and red cells represent alpha cells, with delta cells present to a lesser extent in green. Reg is present in the early small islets that have just budded from the exocrine populations and is not present in the larger more mature islets.

Pancreatic-Cell-Diagram

Source: 2013 Levetan Pierce Distinctions Between Islets of Mice and Men (PDF)
by Claresa S. Levetan, MD, FACE; Susan M. Pierce, MPT, CDE

Taken together, Perle Bioscience, Inc. is conducting a FDA approved Phase 3 trial with an endpoint of insulin independence for the patients. More information on the trial can be seen on our clinical trials page and detailed exclusion and inclusion criteria below.

Exclusion Criteria

  1. Any medical condition that, in the opinion of the investigator, would interfere with safe completion of the trial
  2. Prior administration of immunosuppressants, including in a clinical trial for type 1 diabetes
  3. Participation in any type of therapeutic drug or vaccine clinical trial within the last 12 weeks before randomization at Study Day 0
  4. Currently taking any prescription medications, vitamins or herbal supplements that are contraindicated for Cyclosporine or Omeprizole
  5. Pregnant females or lactating females
  6. Current therapy with GLP-1 receptor agonists (e.g., exenatide or pramlintide), or any other agents that might stimulate pancreatic beta cell regeneration or insulin secretion
  7. Current treatment with oral antidiabetic agents
  8. Evidence of active or latent tuberculosis
  9. Vaccination with a live virus or organism within the 8 weeks before randomization continuing through week 24 of the study
  10. Influenza vaccination with a killed virus, including booster vaccinations, within 4 weeks before or after each dosing cycle
  11. Vaccination with other antigens or killed organisms within 8 weeks before or after each dosing cycle
  12. Any infectious mononucleosis-like illness within the 6 months before randomization
  13. Systolic or diastolic blood pressure >150 mmHg and 90 mmHg, respectively, as measured by an appropriately sized cuff
  14. >95% percentile for height/weight
  15. Worsening retinopathy, angina, or congestive heart failure
  16. A history or presence of acute or chronic pancreatitis
  17. A history or presence of any illness, disease, or condition that could impact patient safety or evaluability of drug effect, in the Investigator’s opinion
  18. An episode of severe hypoglycemia (defined as a change in mental status requiring assistance) during the prior 30 days
  19. An episode of diabetic ketoacidosis during the prior 6 months
  20. Received any new hypoglycemic medications within the past 3 months
  21. An aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin level >2 times the upper limit of normal (ULN)
  22. A blood urea nitrogen (BUN) level >50 mg/dL or a serum creatinine level >1.3 mg/dL
  23. A serum amylase level >1.5 times the ULN or a serum lipase level >2 times the ULN
  24. A history of substance abuse or dependence in the past year as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM Vi) criteria.

Inclusion Criteria

Patients will be considered as having “recent onset” type 1 diabetes and are between the ages of 10 and 20, will be included for study if they meet the following criteria:

  1. Subjects 10-20 years old.
  2. Are able to read, understand, and provide signed informed consent (subjects under the age of 18, shall have an acceptable surrogate capable of giving consent on the subject’s behalf)
  3. Body weight > 30 kg
  4. Diagnosis of diabetes mellitus according to the American Diabetes Association (ADA) criteria
  5. Diagnosis of new onset type 1 diabetes within 12 weeks of symptoms
  6. Randomization on Study Day 0 within 12 weeks of the first visit to any physician for symptoms or signs of diabetes
  7. Requires insulin for T1DMbetween diagnosis and administration of study drug
  8. Diagnosis of T1DM as evidenced by one positive result on testing for any of the following antibodies at screening: Islet-cell autoantibodies 512 (ICA512)/islet antigen-2 (IA-2), Glutamic Acid Decarboxylase (GAD) autoantibodies, Insulin autoantibodies or Zinc Transporter 8 Antibody (ZnT8)
  9. Glucagon stimulated C-peptide greater than 0.6 ng/mL=0.2nmol/L=200 pmol/L=0.2 pmol/mL
  10. Females must have a negative pregnancy test and practice acceptable contraception [e.g., oral, intramuscular, or implanted hormonal contraception, sexual partner with nonreversed vasectomy (with azoospermia in 2 tests), 2 barrier methods (e.g., condom, diaphragm, or spermicide), or intrauterine device] or be post-menopausal (at least 1 year without spontaneous menses) or surgically sterile (tubal ligation or hysterectomy at least 6 months prior to enrollment)]. Females of childbearing potential must undergo pregnancy testing within 24 hours prior to administration of the first dose of study drug.

References

For full references please contact us here.

  1. http://jdrf.org/about-jdrf/fact-sheets/type-1-diabetes-facts/ Accessed 10/1/14
  2. Sundar SS,  Zhang P, Albright A et al. Medical Expenditures Associated With Diabetes Among Privately Insured U.S. Youth in 2007. Diabetes Care. 2011 34:1097-1101.
  3. Rosenthal E. Even small medical advances can mean big jumps in bills. New York Times 2014.  http://www.nytimes.com/2014/04/06/health/even-small-medical-advances-can-mean-big-jumps-in-bills.html?_r=0.  Accessed  8/25/14
  4. Tao B, Massimo Pietropaolo, M Atkinson M. Estimating the cost of type 1 diabetes in the U.S.: A propensity score matching method. PloS One. 2010;5(7)e11501
  5. Dall T, Mann S, Zhang Y. et al. Distinguishing the economic costs associated with type 1 and type 2 diabetes. Population Health Management. 2009;12:103–110.
  6. Levetan C, Pozzilli P, Jovanovic L. et al. Proposal for generating new beta cells in a muted immune environment for type 1 diabetes. Diabetes Metab Res Rev. 2013;29:604-606
  7. Matthews JB, Staeva TP, Bernstein PL. et al. Developing combination immunotherapies for type 1 diabetes: recommendations from the ITN–JDRF Type 1 Diabetes Combination Clinical and Experimental Immunology, Clinical and Experimental Immunology. 2010;160:176–184.
  8. Sobel D, Henzke A, Abbassi V. Cyclosporin and methotrexate therapy induces remission in type 1 diabetes mellitus. Acta Diabetol. 2010;47:243-250.

Photo Credit: “C. H. Best and F. G. Banting ca. 1924″ by Unknown – University of Toronto.
Licensed under Public domain via Wikimedia Commons.

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