The Insulin Independence Trial (IIT) Evaluating the Safety and Efficacy of Oral Cyclosporine and Oral Lansoprazole for Insulin Independence Among Recent Onset Type 1 Diabetes Patients

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2014 by Perle Bioscience, Inc.
Sponsor:
Information provided by (Responsible Party):
Perle Bioscience, Inc.
ClinicalTrials.gov Identifier:
NCT01762644
First received: January 2, 2013
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to determine if oral cyclosporine and oral lansoprazole are effective in rendering recent onset type 1 diabetes patients, insulin independent. This two-arm study was designed to evaluate the safety and efficacy for insulin independence by utilizing the FDA-approved oral immune tolerance agent, Cyclosporine A, and the FDA-approved proton-pump inhibitor, Lansoprazole. Lansoprazole and other proton-pump inhibitors increase gastrin levels. Gastrin was initially shown to have the potential to increase new beta cell formation in 1955 (Zollinger RM and Ellison EH. Ann Surg. 1955;142(4):709-23).

Studies with the immune tolerance agent, Cyclosporine A, previously demonstrated that among recently diagnosed type 1 diabetes patients, insulin independence was achieved in as many as 67.5% of patients within 7 weeks of therapy (Bougneres PF et al. N Engl J Med. 1988:17;318(11):663-70). Cyclosporine A protected the remaining beta cells from further autoimmune attack, but over time, there was limited beta cell regeneration, and insulin was ultimately required by all patients. Therefore, this study proposes the usage of Cyclosporine A with a beta regeneration agent.

Follow-up studies for up to 13 years among 285 type 1 patients utilizing Cyclosporine A for 20 months, did not demonstrate renal or other side effects (Assan R. et al. Diabetes Metab Res Rev. 2002;18(6):464-72). Human clinical trials with gastrin and epidermal growth factor demonstrated reductions in daily insulin requirements by much as 75% within 3 months following four weeks of therapy among existing type 1 diabetes patients (Transition Therapeutics, March 5, 2007 http://www.transitiontherapeutics.com/media/archive.php Accessed January 1, 2013). Lack of the ability to sustain these results was likely due to the ongoing autoimmune attack on the new beta cells generated by therapy. Gastrin alone has been shown to induce beta cell neogenesis from human pancreatic ductal tissue without epidermal growth factor in in-vitro studies (Suarez-Pinzon WL et al. JCEM. 2005;90(6):3401-3409).

Type 1 diabetes is an autoimmune disease. Despite evidence that many different immune tolerance agents have successfully reversed diabetes in rodent type 1 models, none have been successful in sustaining insulin independence in man (Ablamunits V et al. Ann NY Acad Sci. 2007;1103:19-32). The distinctions and complexities of islets in man are far different than that of rodents (Levetan CS and Pierce SM. Endocr Pract. 2012 Nov 27:1-36 Epub ahead of print). We hypothesize that in man, both an immune tolerance agent and a beta regeneration agent are required to sustain insulin independence.

Based upon proton-pump inhibitors having been shown to increase plasma gastrin levels up to 10-fold, this clinical trial utilizes the oral proton-pump inhibitor, Lansoprazole. This study will determine the safety and efficacy of Cyclosporine A used with and without Lansoprazole to determine the impact on insulin independence among recently diagnosed patients with type 1 diabetes.

Cyclosporine A is utilized to protect the new beta cells formed by Lansoprazole. The combination of the two therapies may render reductions in insulin requirements and have a greater impact on sustained insulin independence than previously reported with Cyclosporine A or gastrin alone among type 1 patients.

This 24-week study with evaluation at 24 weeks for insulin independence, consists of two treatment arms:

  • Oral Lansoprazole/Oral Cyclosporine
  • Oral Placebo/Oral Placebo

It is hypothesized that the combination of oral Cyclosporine A and oral Lansoprazole will safely render significantly more patients with existing type 1 diabetes, insulin independent and may serve as a novel and innovative treatment approach for recently diagnosed patients with type 1 diabetes utilizing two FDA-approved therapies.


Condition Intervention Phase
Type 1 Diabetes
Drug: Oral Cyclosporine A and Oral Lansoprazole
Drug: Oral Placebos
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A PhaseIIB/III, Randomized, Double-Blind, Multinational, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Diminishing Insulin Requirements Utilizing Oral Cyclosporine With Oral Lansoprazole in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Perle Bioscience, Inc.:

Primary Outcome Measures:
  • Glucagon stimulated C-peptide (area under the curve) among recently diagnosed patients treated with oral cyclosporine and oral lansoprazole [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Insulin Independence among recently diagnosed patients treated with oral cyclosporine and oral lansoprazole [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 130
Study Start Date: February 2015
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral Cyclosporine and Oral Lansoprazole Drug: Oral Cyclosporine A and Oral Lansoprazole
Oral Cyclosporine A dosed at 5.0 mg/kg/day in two divided doses and adjusted based on trough levels. Lansoprazole dosed at 60 mg daily in two divided doses for patients 8-16 years of age and 120 mg daily in two divided doses for patients aged 17-30. At 24 weeks, all patients who are insulin independent will be given the option to continue on a safety extension study with active drugs for an additional 24 weeks with follow up. Patients who are not insulin independent at 24 weeks will be followed for additional secondary endpoints for a total of 24 more weeks.
Placebo Comparator: Oral Placebos Drug: Oral Placebos
Two oral placebos are provided to patients twice daily. The placebos may be in the form of pills/capsules or oral suspension.

  Eligibility

Ages Eligible for Study:   8 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects 8-30 years old for subjects under the age of 18, shall have an acceptable surrogate capable of giving consent on the subject's behalf
  2. Body weight > 30 Kg
  3. Diagnosis of diabetes mellitus according to the American Diabetes Association (ADA) criteria
  4. Randomization on Study Day 0 within 12 weeks of first visit to any physician for symptoms or signs of diabetes
  5. Requires insulin for T1DM or has required insulin at some time between diagnosis and administration of study drug
  6. 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, or Insulin autoantibodies (in subjects on insulin for more than 2 weeks, ICA512/IA-2 or GAD
  7. C-peptide greater than 0.2nM/0.6 ng/mL
  8. Females must be post-menopausal (at least 1 year without spontaneous menses) or surgically sterile (tubal ligation or hysterectomy at least 6 months prior to enrollment), or to 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]. Females of childbearing potential must undergo pregnancy testing within 24 hours prior to administration of the first dose of study drug.

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 immune tolerance therapy or immune tolerance 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. Pregnant females or lactating females who intend to provide their own breast milk to the baby during the study
  5. 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
  6. Current treatment with oral antidiabetic agents
  7. Evidence of active or latent tuberculosis
  8. Vaccination with a live virus or organism within the 8 weeks before randomization continuing through week 52 of the study
  9. Influenza vaccination with a killed virus, including booster vaccinations, within 4 weeks before or after each dosing cycle
  10. Vaccination with other antigens or killed organisms within 8 weeks before or after each dosing cycle Any infectious mononucleosis-like illness within the 6 months before randomization
  11. Systolic or diastolic blood pressure >150 mmHg and 90 mmHg, respectively, as measured by an appropriately sized cuff
  12. A body mass index (BMI) >28 kg/m2
  13. Worsening retinopathy, angina, or congestive heart failure
  14. A history or presence of acute or chronic pancreatitis
  15. 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
  16. An episode of severe hypoglycemia (defined as a change in mental status requiring assistance) during the prior 30 days
  17. An episode of diabetic ketoacidosis during the prior 6 months;
  18. Received any new hypoglycemic medications within the past 3 months
  19. An aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin level >2 times the upper limit of normal (ULN)
  20. A blood urea nitrogen (BUN) level >50 mg/dL or a serum creatinine level >1.4 mg/Dl
  21. A serum amylase level >1.5 times the ULN or a serum lipase level >2 times the ULN
  22. A history of substance abuse or dependence in the past year as defined by the Diagnostic and Statistical Manual of Mental Disorders,(DSM V) criteria.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01762644

Contacts
Contact: Claresa S. Levetan, MD (703) 568-4222 ClaresaLevetanMD@PerleBioscience.com

Sponsors and Collaborators
Perle Bioscience, Inc.
Investigators
Principal Investigator: Claresa S. Levetan, MD Perle Bioscience, Inc.
  More Information

Additional Information:
Publications:
Responsible Party: Perle Bioscience, Inc.
ClinicalTrials.gov Identifier: NCT01762644     History of Changes
Other Study ID Numbers: Perle-1101
Study First Received: January 2, 2013
Last Updated: August 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Perle Bioscience, Inc.:
Type 1 Diabetes
Insulin Independence
Beta Regeneration
Immune Tolerance Agent
Lanzoprazole
Cyclosporine

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Insulin
Cyclosporins
Cyclosporine
Lansoprazole
Dexlansoprazole
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014