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

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

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 the investigators 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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Tauroursodeoxycholic Acid (TUDCA); Drug: Sugar Pill (placebo)

Detailed 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 a 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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Naomi Berrie Diabetes Center, Columbia University, 1150 St. Nicholas Ave.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Taurourodeoxycholic Acid (TUDCA); TUDCA 1750 mg/day x 12 months	Drug: Tauroursodeoxycholic Acid (TUDCA); TUDCA at 1750 mg/day x 12 months; Other Names: Taurolite; TUDCA
Placebo Comparator: Sugar pill (placebo); Placebo at same dose, frequency, and duration as experimental treatment	Drug: Sugar Pill (placebo); Placebo; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in C-peptide Measurement as Reflection of Insulin Secretion at 6 Months	The primary endpoint will be the change from baseline in area under the stimulated C-peptide curve over the first 2 hours of a 4- hour mixed meal tolerance test conducted at 6 months.	Baseline and 6 months
Change in C-peptide Measurement as Reflection of Insulin Secretion at 12 Months	The primary endpoint will be the change from baseline in area under the stimulated C-peptide curve over the first 2 hours of a 4- hour mixed meal tolerance test conducted at 12 months.	Baseline and 12 months
Change in C-peptide Measurement as Reflection of Insulin Secretion at 18 Months	The primary endpoint will be the change from baseline in area under the stimulated C-peptide curve over the first 2 hours of a 4- hour mixed meal tolerance test conducted at 18 months	Baseline and 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Liver Function Test Abnormalities	Measure liver function tests at 6 and 12 months and at 6 months after drug or placebo is stopped to ensure that no abnormalities (liver function blood tests outside of normal reference range) of liver function occur with the drug.	18 months
Change in Insulin Use at 6 Months	Change in insulin use from baseline at 6 months	Baseline and 6 months
Change in Insulin Use at 12 Months	Change in insulin use from baseline at 12 months	Baseline and 12 months
Change in Insulin Use at 18 Months	Change in insulin use from baseline at 18 months	Baseline and 18 months
Change in HbA1c at 6 Months	Change in HbA1c from baseline at 6 months	Baseline and 6 months
Change in HbA1c at 12 Months	Change in HbA1c from baseline at 12 months	Baseline and 12 months
Change in HbA1c at 18 Months	Change in HbA1c from baseline at 18 months	Baseline and 18 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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. The investigators will measure markers of endoplasmic reticulum stress in beta cells taken from skin biopsies from subjects before treatment with TUDCA or placebo.	1 week

Collaborators and Investigators

• Sponsor: Robin Goland, MD
• Collaborators: Juvenile Diabetes Research Foundation
• Investigators: Principal Investigator: Robin Goland, MD, Columbia University; Principal Investigator: Rudolph Leibel, MD, Columbia University

Publications and helpful links

General Publications

• Rosa LRO, Vettorazzi JF, Zangerolamo L, Carneiro EM, Barbosa HCL. TUDCA receptors and their role on pancreatic beta cells. Prog Biophys Mol Biol. 2021 Dec;167:26-31. doi: 10.1016/j.pbiomolbio.2021.09.003. Epub 2021 Sep 20.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: August 13, 2014
• First Submitted That Met QC Criteria: August 15, 2014
• First Posted (Estimated): August 18, 2014

Study Record Updates

• Last Update Posted (Actual): June 5, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: type 1 diabetes (T1D); endoplasmic reticulum (ER) stress; induced pluripotential stem (iPS) cells; Tauroursodeoxycholic Acid (TUDCA)
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 1; Anti-Infective Agents; Gastrointestinal Agents; Antiviral Agents; Cholagogues and Choleretics; Ursodoxicoltaurine
• Other Study ID Numbers: AAAN2402

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: primary data to be shared
• IPD Sharing Time Frame: 2021
• IPD Sharing Access Criteria: email rsg2@columbia.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR