NCT06025630

Targeting Endoplasmic Reticulum Stress in Human Hypertension

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: University of North Texas Health Science Center · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

There is strong evidence suggesting that endoplasmic reticulum stress contributes to neurogenic and vascular hypertension in various animal models, however this has never been explored in humans. Therefore, this project will fill this gap by performing a single-blind, placebo-controlled trial in humans with hypertension.

Detailed description

The endoplasmic reticulum is a multipurpose organelle found in most human cells, including those in the brain and the endothelium of blood vessels. One of the primary functions of the endoplasmic reticulum is the posttranslational folding of new proteins and the reprocessing of misfolded or damaged proteins. Physiological and pathophysiological conditions can lead to the accumulation of unfolded/misfolded proteins, thus triggering the unfolded protein response which is a quality control system that maintains endoplasmic reticulum homeostasis. However, with prolonged or severe exposure to endoplasmic reticulum stress inducers, the unfolded protein response can augment the formation of reactive oxygen species, inflammatory mediators, and transcription factors that trigger sympathetic overactivity and induce endothelial dysfunction. There is strong evidence suggesting that endoplasmic reticulum stress contributes to neurogenic and vascular hypertension in various animal models, however this has never been explored in humans. This proposal builds on prior work in which the investigators pharmacologically augmented circulating concentrations of the potent endoplasmic reticulum stress inhibitor, tauroursodeoxycholic acid (TUDCA) and the development of an assay/test to quantify endoplasmic reticulum stress in cutaneous biopsy samples. This study will accomplish the following Specific Aims: 1. Examine if endoplasmic reticulum stress inhibition, via chronic ingestion of tauroursodeoxycholic acid, will attenuate 24h blood pressure in humans with elevated (120-129/\<80 mmHg) or stage 1 (130-140/80-90 mmHg) hypertension. 2. Examine the extent to which endoplasmic reticulum stress inhibition alters neurovascular control in the participants of Aim 1. Independent of the contribution to blood pressure regulation, neurovascular function is considered a key risk factor for cardiovascular morbidity and mortality. As such, the outcome of Aim 2, while providing mechanistic insight into the blood pressure lowering effect of endoplasmic reticulum stress inhibition, should be considered independent of the outcomes of Aim 1.

Conditions

• Hypertension

Interventions

Type	Name	Description
DRUG	TUDCA	Endoplasmic reticulum stress will be inhibited by chronic (8 weeks) oral ingestion of the dietary supplement tauroursodeoxycholic acid (TUDCA; 1,750 mg/day)
DRUG	Placebo	Placebo pills containing microcrystalline cellulose will be ingested over the course of the 8 week intervention.

Timeline

• Start date: 2023-08-15
• Primary completion: 2028-12-31
• Completion: 2028-12-31
• First posted: 2023-09-06
• Last updated: 2025-03-28

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study