HypertensionPhase 1/2NCT06025630
Targeting Endoplasmic Reticulum Stress in Human Hypertension
A Phase 1/2 study testing TUDCA in people with Hypertension, run by University of North Texas Health Science Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypertension
- What is being tested?
- TUDCA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Aug 2023to 31 Dec 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 to 80 years of age
- No tobacco/nicotine use within preceding 6 months (e.g., cigarettes, chewing tobacco, nicotine gum or patches)
- Systolic blood pressure <140 mmHg; diastolic blood pressure <90 mmHg (obtained at the Screening and Familiarization Visit)
- Normal 12-lead ECG (obtained at the Screening and Familiarization Visit and reviewed by a board-certified physician)
- Normal clinical results from a medical exam reviewed by a board-certified physician (e.g., General Health Questionnaire obtained at the Screening and Familiarization Visit)
- Body mass index (BMI) <35 unless athletic/muscular build; calculation = body weight (kg)/height (m2);
- Females only: documentation of a negative pregnancy test prior to the familiarization and experimental sessions unless post-menopausal
Who cannot join
- Not meeting the defined age criteria
- Body mass index (BMI) >35 unless athletic/muscular build; calculation = body weight (kg)/height (m2)
- Any tobacco/nicotine use within the last 6 months (e.g., cigarettes, chewing tobacco, nicotine gum or patches)
- Positive pregnancy test
- Females with an erratic/irregular menstrual cycle
- Females who are breastfeeding
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- Women who are prescribed a continually releasing hormonal contraceptive (e.g. NuvaRingTM or other hormone releasing vaginal rings, Depo Provera shot, or birth control implants such as Nexplanon)
- Subjects who weigh less than 80 lbs.
- Use of prescription drugs, non-prescription drugs, dietary supplements or herbal medicines known to alter vascular function unless cleared prior to the study
- Use of beta blockers
- Daily use of bronchodilators
- Use of anti-coagulant therapy
- Implanted medical devices (e.g. cardiac pacemaker)
- Current or past history of hyperthyroidism, or other thyroid hormone-related disease
- Current use of hormone replacement therapy (e.g., estrogen, testosterone)
- HbA1c >5.6
- Resting systolic blood pressure of <100 mmHg; >140mmHg or diastolic blood pressure >90mmHg
- Abnormal 12-lead ECG or uncontrolled heart rhythm issues causing symptoms, or an unstable blood pressure
- History of cerebrovascular abnormalities (e.g., prior stroke, transient ischemic attacks, epilepsy)
- Known history of atherosclerosis of the carotid arteries (i.e., plaque formation)
- History of concussion and or other loss of consciousness within the preceding 30 days
- Autonomic dysfunction (e.g., Shy-Drager Syndrome, Bradbury-Eggleston syndrome, sinus arrhythmia, idiopathic orthostatic hypotension, fainting disorder)
- Respiratory illnesses (e.g., chronic asthma (including exercise-induced asthma), Chronic Obstructive Pulmonary Disease, Reactive Airway Disease)
- Any prior history of anaphylaxis, not just prior reactions to the materials used in this study
- Severe phobia of needles
- Latex allergy aa) Known allergies or sensitivities to substances used in the study (e.g., Lidocaine HCL, sodium nitroprusside, acetylcholine, phentolamine, L-NAME, TUDCA, or related drugs) bb) Donated blood within the last 60 days cc) History or family history of abnormal blood clotting, clots in deep veins in the legs or pelvis, or blood clots to the lungs dd) History of alcohol or drug abuse which inhibits the subject's ability to complete this study ee) Individuals who have had mastectomies ff) History of methemoglobinemia gg) Current diagnosis of anemia hh) Current Fever (oral temp >99.5 °F/ 37.5 °C) ii) Current use of PDE3 inhibitors (e.g., Viagra) or soluble guanylate cyclase (sGC) stimulators (e.g., riociguat), or unwillingness to withhold medication for 2 weeks prior to laboratory testing jj) Current diagnosis of cancer kk) Cardiac surgery or cardiac events (e.g., coronary artery bypass graft surgery, myocardial infarction, heart failure) ll) Diagnosis of neurological disease or cognitive dysfunction
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of North Texas Health Science Center
Fort Worth, Texas, 76107
Steven A Romero, PhD, 8177355159, steven.romero@unthsc.edu
Bella Ruiz, BS, 8177352088, YsabellaRuiz@my.unthsc.edu
About this study
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.
Read the 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:
- 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.
- 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
- Being tested
- TUDCA, Placebo
- Keywords
- high blood pressure, tauroursodeoxycholic acid (TUDCA), endoplasmic reticulum
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TUDCADrug
Endoplasmic reticulum stress will be inhibited by chronic (8 weeks) oral ingestion of the dietary supplement tauroursodeoxycholic acid (TUDCA; 1,750 mg/day)
PlaceboDrug
Placebo pills containing microcrystalline cellulose will be ingested over the course of the 8 week intervention.
| Study group | Role | What they receive |
|---|---|---|
| Endoplasmic Reticulum Stress Inhibition | Experimental | Not described Receives: Drug: TUDCA |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
24 hour Blood Pressure
Systolic and diastolic blood pressure will be measured twice per hour during the day and once per hour at night using a portable cuff.
Measured: Within 1-2 weeks before and after intervention or placebo
Secondary outcomes (4)
Neurovascular Function
The microdialysis technique will be used to examine neurovascular function. To do this, blood flow will be measured in response to the local infusion of pharmacological agents that alter blood flow.
Measured: Within 1-2 weeks before and after intervention or placebo
Cardiac output
The amount of blood pumped from the heart each minute (i.e., cardiac output) be measured via inert gas (nitrous oxide) rebreathing
Measured: Within 1-2 weeks before and after intervention or placebo
Arterial Pulse Wave Velocity
Resting arterial compliance/stiffness will be assessed by measuring Doppler derived pulse wave velocity.
Measured: Within 1-2 weeks before and after intervention or placebo
Endoplasmic Reticulum Stress
Endoplasmic reticulum stress will be quantified by measuring the mRNA expression of spliced X-box binding protein 1 in a cutaneous biopsy sample obtained before and after the intervention.
Measured: Within 1-2 weeks before and after intervention or placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2023
- Study start15 Aug 2023
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study uses a single-blind, placebo-controlled model.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of North Texas Health Science Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Steven A. Romero, University of North Texas Health Science Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06025630
- Sponsor's protocol ID
- ERX:2023-063
- Status last verified
- Mar 2025
- First submitted
- 23 Aug 2023
- Last updated
- 28 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Endoplasmic Reticulum Stress in Human Hypertension
- ClinicalTrials.gov ID
- NCT06025630
- Acronym / sponsor ID
- ERX:2023-063
- Conditions
- Hypertension
- Keywords
- high blood pressure, tauroursodeoxycholic acid (TUDCA), endoplasmic reticulum
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- University of North Texas Health Science CenterUniversity, hospital or other
- Study start
- 15 Aug 2023 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 6 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- This study uses a single-blind, placebo-controlled model.
| Arm | Type | Receives |
|---|---|---|
| Endoplasmic Reticulum Stress Inhibition | Experimental | Drug: TUDCA |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 18 to 80 years of age
- No tobacco/nicotine use within preceding 6 months (e.g., cigarettes, chewing tobacco, nicotine gum or patches)
- Systolic blood pressure <140 mmHg; diastolic blood pressure <90 mmHg (obtained at the Screening and Familiarization Visit)
- Normal 12-lead ECG (obtained at the Screening and Familiarization Visit and reviewed by a board-certified physician)
- Normal clinical results from a medical exam reviewed by a board-certified physician (e.g., General Health Questionnaire obtained at the Screening and Familiarization Visit)
Key exclusion criteria (26 listed)
- Not meeting the defined age criteria
- Body mass index (BMI) >35 unless athletic/muscular build; calculation = body weight (kg)/height (m2)
- Any tobacco/nicotine use within the last 6 months (e.g., cigarettes, chewing tobacco, nicotine gum or patches)
- Positive pregnancy test
- Females with an erratic/irregular menstrual cycle
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TUDCAEndoplasmic reticulum stress will be inhibited by chronic (8 weeks) oral ingestion of the dietary supplement tauroursodeoxycholic acid (TUDCA; 1,750 mg/day) | Drug | Endoplasmic Reticulum Stress Inhibition |
| PlaceboPlacebo pills containing microcrystalline cellulose will be ingested over the course of the 8 week intervention. | Drug | Placebo |
Primary outcome
24 hour Blood Pressure
Time frame: Within 1-2 weeks before and after intervention or placebo
Systolic and diastolic blood pressure will be measured twice per hour during the day and once per hour at night using a portable cuff.
4 secondary outcomes
Neurovascular Function
Time frame: Within 1-2 weeks before and after intervention or placebo
Cardiac output
Time frame: Within 1-2 weeks before and after intervention or placebo
Arterial Pulse Wave Velocity
Time frame: Within 1-2 weeks before and after intervention or placebo
Endoplasmic Reticulum Stress
Time frame: Within 1-2 weeks before and after intervention or placebo
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
University of North Texas Health Science Center
Fort Worth, United States
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TUDCA in people with Hypertension, run by University of North Texas Health Science Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24 hour Blood Pressure (time frame: Within 1-2 weeks before and after intervention or placebo). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2025.