Tauroursodeoxycholic Acid (TUDCA) in New-Onset Type 1 Diabetes

Type 1 Diabetes Clinical Trial

Official title:

Clinical Investigation of Efficacy of Tauroursodeoxycholic Acid (TUDCA) to Enhance Pancreatic Beta Cell Survival In Type 1 Diabetes by Reducing Endoplasmic Reticulum Stress

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02218619
• Other study ID #: AAAN2402
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 2015
• Est. completion date: October 1, 2019

Study information

• Verified date: December 2018
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Clinically, the ability to slow or prevent beta cell demise can prevent or improve the course of type 1 diabetes. The immune-mediated destruction of beta cells that is an apparent major pathological basis for the disease, has led to efforts to prevent or suppress this immune assault. Here we propose to buttress the beta cell's capacity to withstand this assault by improving the function of the endoplasmic reticulum stress resolving mechanisms within these cells. The ability to do so could have a major impact on preventive and therapeutic strategies for type 1 diabetes (and possibly other types of diabetes). The type of endoplasmic reticulum stress relieving agent (TUDCA) proposed here could ultimately be applied on an anticipatory basis to individuals at high risk for type 1 diabetes.

Description:

Reducing endoplasmic reticulum stress will promote beta cell survival in new-onset type 1 diabetes.

The primary aim is to test the clinical efficacy of an already approved agent, TUDCA, re-purposed to reduce endoplasmic reticulum stress and improve beta cell survival in patients with new onset type 1 diabetes. The primary endpoint of this proposed double-blinded randomized placebo-controlled pilot study is c-peptide measured after mixed meal stimulation test at randomization and then at 6 and 12 months of treatment with TUDCA compared to treatment with placebo and at 6 months following treatment.

TUDCA is an oral medication with an excellent safety profile that is approved for use in Europe for gall stones and liver disease. The drug and similar compounds has been used in children, as young as newborns, and in adults. TUDCA's ability to lower endoplasmic reticulum stress has only recently been recognized and will be applied to new-onset type 1 diabetes in this proposal. If this pilot trial is successful, future studies could include broadening the recipients to antibody-positive pre-type 1 diabetes patients and/or combining TUDCA with other agents shown to have a beneficial effect on insulin secretion in new-onset type 1 diabetes.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: October 1, 2019
• Est. primary completion date: October 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Type 1 diabetes according to American Diabetes Association criteria

• Diagnosis of type 1 diabetes within 100 days of randomization

• One positive diabetes-related autoantibody

• Ages 18-45 years

Exclusion Criteria:

• Drugs known to affect glucose other than insulin

• Stimulated C-peptide levels < 0.2 pmol/ml measured during a mixed meal tolerance test conducted at least 21 days from diagnosis of diabetes and within one month (37 days) of randomization to either TUDCA or placebo.

• Women during pregnancy

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Drug:
• Tauroursodeoxycholic Acid (TUDCA)
TUDCA at 1750 mg/day x 12 months
• Sugar Pill (placebo)
Placebo

Locations

Country	Name	City	State
United States	Naomi Berrie Diabetes Center, Columbia University, 1150 St. Nicholas Ave.	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Robin Goland, MD	Juvenile Diabetes Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	C-peptide measurement as reflection of insulin secretion	The primary endpoint will be the area under the stimulated C-peptide curve over the first 2 hours of a 4- hour mixed meal tolerance test conducted at screening, and during the 12 months of drug treatment at 6 and12 months and at 6 months after drug or placebo is stopped.	18 months
Secondary	Endoplasmic reticulum stress	It is believed that the autoimmune assault of new onset type 1 diabetes leads to stress to the part of the beta cell that folds proteins; referred to as endoplasmic reticulum stress. When endoplasmic reticulum stress increases, changes in protein levels in beta cells occur. We will measure markers of endoplasmic reticulum stress in beta cells taken from skin biopsies taken from subjects before treatment with TUDCA or placebo.	1 week
Secondary	liver function tests	We will measure liver function tests at 6 and 12 months and at 6 months after drug or placebo is stopped to ensure that no abnormalities of liver function occur with the drug.	18 months