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

NCT00837759 | Terminated Phase 2 Results

• 2 other identifiers: 09005609-DK-0056
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus Type 1; Autoimmune Diabetes

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change in C-peptide

  6 months following the protocol subject's randomization/treatment initiation

Secondary Outcomes (5)

• Glycemia Control (Change in HbA1c Level)

  6 months following the protocol subject's randomization/treatment initiation

• Change in Insulin Dose

  6 months following the protocol subject's randomization/treatment initiation

• Change in Anti-GAD Autoantibody Titers

  6 months following the protocol subject's randomization/treatment initiation

• Change in Anti-IA2 Titer

  6 months following the protocol subject's randomization/treatment initiation

• Change in ZnT8 Autoantibody Titer

  6 months following the protocol subject's randomization/treatment initiation

Study Arms (1)

T1D group

OTHER

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.

Drug: Insulin; Drug: Lansoprazole; Drug: Sitagliptin; Biological: Diamyd; Drug: GAD65 (Diamyd)

Interventions

Insulin DRUG

T1D group

Lansoprazole DRUG

T1D group

Sitagliptin DRUG

T1D group

Diamyd BIOLOGICAL

T1D group

GAD65 (Diamyd) DRUG

T1D group

Eligibility Criteria

• Age: 16 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• Ages between 16 and 30 years, inclusive
• Random plasma C-peptide level of equal to or greater than 0.20 nmol/L
• Willingness and ability to institute intensive insulin-based glucose management.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Bach JF, Chatenoud L. Tolerance to islet autoantigens in type 1 diabetes. Annu Rev Immunol. 2001;19:131-61. doi: 10.1146/annurev.immunol.19.1.131.

  PMID: 11244033 BACKGROUND

• Lernmark A, Barmeier H, Dube S, Hagopian W, Karlsen A, Wassmuth R. Autoimmunity of diabetes. Endocrinol Metab Clin North Am. 1991 Sep;20(3):589-617.

  PMID: 1935920 BACKGROUND

• Mathis D, Vence L, Benoist C. beta-Cell death during progression to diabetes. Nature. 2001 Dec 13;414(6865):792-8. doi: 10.1038/414792a.

  PMID: 11742411 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Interventions

Insulin; Lansoprazole; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Triazoles; Azoles; Pyrazines

Results Point of Contact

• Title: Dr. Rana Malek
• Organization: NIDDK, National Institutes of Health

malekr@mail.nih.gov

3015945288

Study Officials

• Balow James, MD

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Director Intramural NIDDK

Study Record Dates

• First Submitted: February 4, 2009
• First Posted: February 5, 2009
• Study Start: February 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: January 3, 2013
• Results First Posted: October 24, 2012

Record last verified: 2012-12

Locations

US (1)