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

Phase 2

Completed

Interventions: Drug: Tauroursodeoxycholic Acid (TUDCA)
Drug: Sugar Pill (placebo)

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 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.

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.

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
Taurourodeoxycholic Acid (TUDCA)	Tauroursodeoxycholic Acid (TUDCA)	TUDCA 1750 mg/day x 12 months
Sugar pill (placebo)	Sugar Pill (placebo)	Placebo at same dose, frequency, and duration as experimental treatment

Primary Outcome Measures

Name	Time	Method
Change in C-peptide Measurement as Reflection of Insulin Secretion at 6 Months	Baseline and 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.
Change in C-peptide Measurement as Reflection of Insulin Secretion at 12 Months	Baseline and 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.
Change in C-peptide Measurement as Reflection of Insulin Secretion at 18 Months	Baseline and 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

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Liver Function Test Abnormalities	18 months	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.
Change in Insulin Use at 6 Months	Baseline and 6 months	Change in insulin use from baseline at 6 months
Change in Insulin Use at 12 Months	Baseline and 12 months	Change in insulin use from baseline at 12 months
Change in Insulin Use at 18 Months	Baseline and 18 months	Change in insulin use from baseline at 18 months
Change in HbA1c at 6 Months	Baseline and 6 months	Change in HbA1c from baseline at 6 months
Change in HbA1c at 12 Months	Baseline and 12 months	Change in HbA1c from baseline at 12 months
Change in HbA1c at 18 Months	Baseline and 18 Months	Change in HbA1c from baseline at 18 months

Locations (1): Naomi Berrie Diabetes Center, Columbia University, 1150 St. Nicholas Ave.
🇺🇸
New York, New York, United States
Naomi Berrie Diabetes Center, Columbia University, 1150 St. Nicholas Ave.
🇺🇸New York, New York, United States