Tauroursodeoxycholic Acid (TUDCA) in New-Onset Type 1 Diabetes
Primary Purpose
Type 1 Diabetes
Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tauroursodeoxycholic Acid (TUDCA)
Sugar Pill (placebo)
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes focused on measuring type 1 diabetes (T1D), endoplasmic reticulum (ER) stress, induced pluripotential stem (iPS) cells, Tauroursodeoxycholic Acid (TUDCA)
Eligibility Criteria
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
Sites / Locations
- Naomi Berrie Diabetes Center, Columbia University, 1150 St. Nicholas Ave.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Taurourodeoxycholic Acid (TUDCA)
Sugar pill (placebo)
Arm Description
TUDCA 1750 mg/day x 12 months
Placebo at same dose, frequency, and duration as experimental treatment
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT02218619
First Posted
August 13, 2014
Last Updated
December 3, 2018
Sponsor
Robin Goland, MD
Collaborators
Juvenile Diabetes Research Foundation
1. Study Identification
Unique Protocol Identification Number
NCT02218619
Brief Title
Tauroursodeoxycholic Acid (TUDCA) in New-Onset Type 1 Diabetes
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Unknown status
Study Start Date
August 2015 (undefined)
Primary Completion Date
October 1, 2019 (Anticipated)
Study Completion Date
October 1, 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Robin Goland, MD
Collaborators
Juvenile Diabetes Research Foundation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
type 1 diabetes (T1D), endoplasmic reticulum (ER) stress, induced pluripotential stem (iPS) cells, Tauroursodeoxycholic Acid (TUDCA)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Taurourodeoxycholic Acid (TUDCA)
Arm Type
Experimental
Arm Description
TUDCA 1750 mg/day x 12 months
Arm Title
Sugar pill (placebo)
Arm Type
Placebo Comparator
Arm Description
Placebo at same dose, frequency, and duration as experimental treatment
Intervention Type
Drug
Intervention Name(s)
Tauroursodeoxycholic Acid (TUDCA)
Other Intervention Name(s)
TUDCA, Taurolite
Intervention Description
TUDCA at 1750 mg/day x 12 months
Intervention Type
Drug
Intervention Name(s)
Sugar Pill (placebo)
Other Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
C-peptide measurement as reflection of insulin secretion
Description
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.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Endoplasmic reticulum stress
Description
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.
Time Frame
1 week
Title
liver function tests
Description
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.
Time Frame
18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robin Goland, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rudolph Leibel, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Naomi Berrie Diabetes Center, Columbia University, 1150 St. Nicholas Ave.
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
34547326
Citation
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.
Results Reference
derived
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Tauroursodeoxycholic Acid (TUDCA) in New-Onset Type 1 Diabetes
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