NCT02218619

Clinical Investigation of Efficacy of Tauroursodeoxycholic Acid (TUDCA) to Enhance Pancreatic Beta Cell Survival In Type 1 Diabetes by Reducing Endoplasmic Reticulum Stress

Completed Phase 2 Results posted Last updated 19 May 2025

What this trial tests

Phase 2 trial testing Tauroursodeoxycholic Acid (TUDCA) in Type 1 Diabetes in 20 participants. Completed in 31 December 2019.

Timeline

1 August 2015

Primary endpoint
31 December 2019

31 December 2019

Quick facts

Lead sponsor	Robin Goland, MD
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	20
Start date	1 August 2015
Primary completion	31 December 2019
Estimated completion	31 December 2019
Sites	1 location across United States

Drugs / interventions tested

• Tauroursodeoxycholic Acid (TUDCA) — full drug profile →
• Sugar Pill (placebo) — full drug profile →

Conditions studied

• Type 1 Diabetes — all drugs for Type 1 Diabetes →

Sponsor

Robin Goland, MD

Who can join

Adults 18 to 45, any sex, with Type 1 Diabetes. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Change in C-peptide Measurement as Reflection of Insulin Secretion at 6 Months
  Time frame: 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
  Time frame: 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
  Time frame: 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

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Beta Cell Dedifferentiation Induced by IRE1α Deletion Prevents Type 1 Diabetes.
   Lee H, Lee YS, Harenda Q, Pietrzak S, et al · · 2020 · cited 134× · PMID 32220307 · DOI 10.1016/j.cmet.2020.03.002
2. The challenge of modulating β-cell autoimmunity in type 1 diabetes.
   Atkinson MA, Roep BO, Posgai A, Wheeler DCS, et al · · 2019 · cited 126× · PMID 30528099 · DOI 10.1016/s2213-8587(18)30112-8
3. The role of beta-cell dysfunction in early type 1 diabetes.
   Sims EK, Mirmira RG, Evans-Molina C. · · 2020 · cited 65× · PMID 32618633 · DOI 10.1097/med.0000000000000548
4. Type 1 Diabetes TrialNet: A Multifaceted Approach to Bringing Disease-Modifying Therapy to Clinical Use in Type 1 Diabetes.
   Bingley PJ, Wherrett DK, Shultz A, Rafkin LE, et al · · 2018 · cited 59× · PMID 29559451 · DOI 10.2337/dc17-0806
5. Endoplasmic reticulum stress in beta cells and autoimmune diabetes.
   Clark AL, Urano F. · · 2016 · cited 58× · PMID 27718448 · DOI 10.1016/j.coi.2016.09.006
6. Gene expression signatures of target tissues in type 1 diabetes, lupus erythematosus, multiple sclerosis, and rheumatoid arthritis.
   Szymczak F, Colli ML, Mamula MJ, Evans-Molina C, et al · · 2021 · cited 56× · PMID 33523973 · DOI 10.1126/sciadv.abd7600
7. A Stem Cell-Based Screening Platform Identifies Compounds that Desensitize Motor Neurons to Endoplasmic Reticulum Stress.
   Thams S, Lowry ER, Larraufie MH, Spiller KJ, et al · · 2019 · cited 40× · PMID 30446391 · DOI 10.1016/j.ymthe.2018.10.010
8. GRP78 translocation to the cell surface and O-GlcNAcylation of VE-Cadherin contribute to ER stress-mediated endothelial permeability.
   Lenin R, Nagy PG, Jha KA, Gangaraju R. · · 2019 · cited 34× · PMID 31346222 · DOI 10.1038/s41598-019-47246-w