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Novel Therapy to Preserve Beta Cell Function in New Onset Type 1 Diabetes

Primary Purpose

Diabetes Mellitus Type 1, Autoimmune Diabetes

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Insulin

Lansoprazole

Sitagliptin

Diamyd

GAD65 (Diamyd)

About this trial

This is an interventional treatment trial for Diabetes Mellitus Type 1 focused on measuring Type I Diabetes, Preserve Beta Cell Function, Sitagliptin, Lansoprazole, GAD65 (Diamyd), Diabetes, Type 1 Diabetes, T1DM

Eligibility Criteria

16 Years - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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:

Diabetic nephropathy with a creatinine clearance less than 60 cc/min or 24 hour urine albumin greater than 300 mg
Insulin requirements greater than 0.8 units/kg/day at the end of the run-in period
Regular use of a proton pump inhibitor within 3 months of enrollment
Use of GLP-1R agonist or DPP-4 inhibitor within 6 months prior to enrollment
Use of immunosuppressive therapy in the preceding 12 months
Evidence of chronic infection, for example, known human immunodeficiency virus (HIV) or hepatitis
History of any malignancy other than a treated basal or squamous skin cancer
Any chronic medical condition to unduly increase risk for the potential enrollee as judged by study investigators
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
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).

Sites / Locations

National Institutes of Health Clinical Center, 9000 Rockville Pike

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

T1D group

Arm Description

This study was terminated prior to full subject accrual because of changes to study personnel. The original study design was changed from a double-blind, placebo-controlled study to an open-label pilot study in order to collect safety data on enrolled subjects prior to study termination.

Outcomes

Primary Outcome Measures

Change in C-peptide

Secondary Outcome Measures

Glycemia Control (Change in HbA1c Level)

Change in Insulin Dose

Change in Anti-GAD Autoantibody Titers

Change in Anti-IA2 Titer

Change in ZnT8 Autoantibody Titer

Full Information

NCT ID

NCT00837759

First Posted

February 4, 2009

Last Updated

December 31, 2012

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. Study Identification

Unique Protocol Identification Number

NCT00837759

Brief Title

Novel Therapy to Preserve Beta Cell Function in New Onset Type 1 Diabetes

Official Title

Novel Therapy Combining Regenerative Stimuli Immunomodulation to Preserve Beta Cell Function in New Onset Type 1 Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

December 2012

Overall Recruitment Status

Terminated

Why Stopped

Changes to study personnel.

Study Start Date

February 2009 (undefined)

Primary Completion Date

March 2011 (Actual)

Study Completion Date

March 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed Description

Type 1 diabetes (T1D) is the end result of immune mediated beta-cell destruction. It is generally accepted that at the time of T1D is diagnosed, an individual has lost most (60-80%) of his/her beta cell function. The loss of insulin-producing beta cells is believed to occur over a period of months to years and individuals can retain some endogenous insulin production even years after clinical diagnosis of diabetes. The presence of residual beta cell mass may signify a complex interplay between the auto-destructive immune response and the capacity for limited beta cell regeneration. When initiated at T1D onset, immunosuppression has been shown to preserve beta cell function, but with significant and limiting toxicities. Selectively targeting the pathogenic T-cells involved in T1D development and progression could achieve the same objective with less toxicity. Various studies of the non-obese diabetic (NOD) mouse model of spontaneous autoimmune diabetes have demonstrated that administering glutamic acid decarboxylase (GAD65), a beta cell autoantigen, can prevent the immune destruction and delay or prevent diabetes onset. Preclinical studies have also identified several growth factors, including epidermal growth factor (EGF), glucagon-like peptide 1 (GLP-1), and gastrin, that appear to promote beta cell proliferation. We seek to test the potential for preserving beta cell function early in the disease course of T1D by combining antigen-specific immunomodulation with regenerative stimuli.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus Type 1, Autoimmune Diabetes

Keywords

Type I Diabetes, Preserve Beta Cell Function, Sitagliptin, Lansoprazole, GAD65 (Diamyd), Diabetes, Type 1 Diabetes, T1DM

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

7 (Actual)

8. Arms, Groups, and Interventions

Arm Title

T1D group

Arm Type

Other

Arm Description

Intervention Type

Drug

Intervention Name(s)

Insulin

Intervention Type

Drug

Intervention Name(s)

Lansoprazole

Intervention Type

Drug

Intervention Name(s)

Sitagliptin

Intervention Type

Biological

Intervention Name(s)

Diamyd

Intervention Type

Drug

Intervention Name(s)

GAD65 (Diamyd)

Primary Outcome Measure Information:

Title

Change in C-peptide

Time Frame