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

December 3, 2018 updated by: Robin Goland, MD

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 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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
C-peptide measurement as reflection of insulin secretion
Time Frame: 18 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endoplasmic reticulum stress
Time Frame: 1 week
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
liver function tests
Time Frame: 18 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2015

Primary Completion (Anticipated)

October 1, 2019

Study Completion (Anticipated)

October 1, 2019

Study Registration Dates

First Submitted

August 13, 2014

First Submitted That Met QC Criteria

August 15, 2014

First Posted (Estimate)

August 18, 2014

Study Record Updates

Last Update Posted (Actual)

December 4, 2018

Last Update Submitted That Met QC Criteria

December 3, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAN2402

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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