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

Robin Goland, MD

Status and phase

Completed

Phase 2

Conditions

Type 1 Diabetes

Treatments

Drug: Tauroursodeoxycholic Acid (TUDCA)

Drug: Sugar Pill (placebo)

Study type

Interventional

Funder types

Other

Identifiers

NCT02218619

AAAN2402

Details and patient eligibility

About

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.

Full 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.

Enrollment

20 patients

Sex

All

Ages

18 to 45 years old

Volunteers

No Healthy Volunteers

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