Clinical trial NCT02218619: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes
Keywords: type 1 diabetes (T1D)
endoplasmic reticulum (ER) stress
induced pluripotential stem (iPS) cells
Tauroursodeoxycholic Acid (TUDCA)
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2014-08-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in C-peptide Measurement as Reflection of Insulin Secretion at 6 Months
timeFrame: Baseline and 6 months
measure: Change in C-peptide Measurement as Reflection of Insulin Secretion at 12 Months
timeFrame: Baseline and 12 months
measure: Change in C-peptide Measurement as Reflection of Insulin Secretion at 18 Months
timeFrame: Baseline and 18 months
Secondary outcomes:
measure: Number of Participants With Liver Function Test Abnormalities
timeFrame: 18 months
measure: Change in Insulin Use at 6 Months
timeFrame: Baseline and 6 months
measure: Change in Insulin Use at 12 Months
timeFrame: Baseline and 12 months
measure: Change in Insulin Use at 18 Months
timeFrame: Baseline and 18 months
measure: Change in HbA1c at 6 Months
timeFrame: Baseline and 6 months
measure: Change in HbA1c at 12 Months
timeFrame: Baseline and 12 months
measure: Change in HbA1c at 18 Months
timeFrame: Baseline and 18 Months
Other outcomes:
measure: Endoplasmic Reticulum Stress
timeFrame: 1 week
Locations:
city: New York
country: United States
facility: Naomi Berrie Diabetes Center, Columbia University, 1150 St. Nicholas Ave.
state: New York
Study officials:
affiliation: Columbia University
name: Robin Goland, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Rudolph Leibel, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.