- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03878654
Trial of Tauroursodeoxycholic Acid (TUDCA) in Asthma
Asthma is a chronic lung disease that affects millions of people worldwide, including both children and adults. The cause of asthma is not known, but asthma is strongly associated with inflammation of the airways, often caused by allergies. In order to control this inflammation, most people with asthma are treated with inhaled medications that contain steroids. These medications do a good job of helping most people with asthma feel better. However, these medications are expensive, have side effects, and do not control symptoms in all people with asthma. Recently basic science research colleagues have shown that inflammation due to allergies can be reduced in experimental animals by a naturally occurring bile acid. Bile acids are chemicals made in the liver that are involved in maintaining healthy digestion of fat. Since bile acids are made by our bodies, they have become popular as over the counter supplements that are thought to be important in promoting a healthy liver and metabolism. Interestingly, other research has shown that bile acids may help patients with neurological disease and diabetes.
Given all of this information, the investigators propose that a specific bile acid called tauroursodeoxycholic acid (TUDCA) may be helpful in patients with asthma. Before studying this in a clinical trial, the current study is designed to demonstrate that people with asthma can take TUDCA safely and that it doesn't hurt their asthma. The study will involve inviting 12 patients with mild asthma to take TUDCA daily for 12 weeks. During this time the investigators will closely monitor them for any side effects and check their blood and breathing capacity for any signs of detrimental effects. In addition, the investigators will collect cells that line the nose, which are thought to be similar to cells in the airways of the lungs, to see if TUDCA is having any beneficial effects on inflammation. In order to ensure the use of high quality TUDCA, which may or may not be true of over the counter supplements, the investigators have asked the company that is supplying TUDCA for the studies mentioned previously involving neurological disease and diabetes to supply the drug; the brand name is Taurolite. In addition, even though TUDCA is available over the counter, in order to use it for research, the FDA has to approve this use. Accordingly, the investigators have applied for and received permission (IND) from the FDA to use Taurolite for this study.
Study Overview
Detailed Description
Study Design: This study will be a Phase 1, pre-post intervention trial in patients with asthma who will be treated with TUDCA 1750 mg per day for 12 weeks. The investigators have obtained TUDCA from Bruschettini (http://www.bruschettini.com), which is an authorized Italian pharmaceutical company that can provide validation of the drug's manufacture and purity. Bruschettini markets TUDCA under the brand name Taurolite. The investigators have received an IND from the FDA for use of Taurolite in this study (see document).
Protocol: All participants will undergo an initial screening visit by telephone to determine. Participants will then present to the Vermont Lung Center in Colchester for 2 study visits, during which the following testing and information will be obtained:
Visit 1 (Baseline)
- Demographics: age, sex, height, weight
- Concomitant medical problems and medications
- Asthma control by ACT
- Lung function testing: spirometry (FEV1, FVC, FEV1/FVC) (43), forced oscillation technique (FOT) (R5, R20, X5, AX, Fres) (44)
- Fraction of exhaled nitric oxide (FeNO) as a general measure of eosinophilic inflammation(45)
- Blood sample collection for routine chemistries (10 cc), and for analysis of serum markers of inflammation (10 cc).
- Nasal brushing for collection of epithelial cells for analysis of serum markers of ER stress and UPR The participant will then receive a supply of medication, TUDCA 250 mg, to be taken 500 mg with breakfast, 500 mg with lunch, 750 mg with dinner, daily, for 12 weeks.
The participant will also receive a daily diary to use to record daily symptoms of asthma and any side effects, as well as compliance with taking the medication.
Visit 2 (Week 4) and Visit 3 (Week 8)
- Review of diary for side effects, adverse events
- Asthma control by ACT, spirometry, FeNO
- Blood for routine chemistries as part of ongoing safety monitoring Visit 4 (Week 12) All testing as listed for Visit 1 will be repeated, with collection of any remaining drug and all diary data.
Telephone Calls (Weeks 2,6,10) The investigators will call participants every 2 weeks in between study visits to assess tolerability and remind participants to complete their daily diaries. The investigators will use a standardized questionnaire for study coordinators to use during each assessment by telephone to determine whether there have been any adverse events.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Vermont
-
Colchester, Vermont, United States, 05446
- Vermont Lung Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Men and women, aged 18 and older, with a physician diagnosis of asthma
- Current non-smoker with < 10 pack-years smoking history and no smoking within the last year
- Stable asthma control over the last 3 months as defined by Asthma Control Test (ACT) ≥ 20 (40)
- Stable asthma medication regimen over the last 3 months
- FEV1 ≥ 70% predicted
Exclusion Criteria:
- Current smoking or ≥10 pack-years of smoking or any smoking within the last year
- Poor asthma control as defined by ACT< 20
- Exacerbation of disease within previous 4 weeks
- Recent upper respiratory infection within last 4 weeks
- Acute or chronic rhinosinusitis
- Use of chronic nasal corticosteroids, or any use of nasal corticosteroids during the study
- Concomitant heart, lung or GI disease (liver, peptic ulcer) that would potentially jeopardize the safety of the participant or interfere with interpretation of the results
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Tauroursodeoxycholic Acid
TUDCA 1750 mg daily for 12 weeks
|
Naturally occurirng bile acid
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
AST
Time Frame: 12 weeks
|
Liver toxicity by AST
|
12 weeks
|
ALT
Time Frame: 12 weeks
|
Liver toxicity by ALT
|
12 weeks
|
alkaline phosphatase
Time Frame: 12 weeks
|
Liver toxicity by alkaline phosphatase
|
12 weeks
|
total bilirubin
Time Frame: 12 weeks
|
Liver toxicity by total bilirubin
|
12 weeks
|
BUN
Time Frame: 12 weeks
|
Renal toxicity by BUN
|
12 weeks
|
creatinine
Time Frame: 12 weeks
|
renal function by creatinine
|
12 weeks
|
CBC
Time Frame: 12 weeks
|
Hematology toxicity by CBC
|
12 weeks
|
total cholesterol
Time Frame: 12 weeks
|
Lipid toxicity by total cholesterol
|
12 weeks
|
LDL
Time Frame: 12 weeks
|
Lipid toxicity by LDL
|
12 weeks
|
HDL
Time Frame: 12 weeks
|
Lipid toxicity by HDL
|
12 weeks
|
triglycerides
Time Frame: 12 weeks
|
Lipid toxicity by triglycerides
|
12 weeks
|
symptom diary
Time Frame: 12 weeks
|
symptoms and side effects
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
ACT score
Time Frame: 12 weeks
|
Asthma control by ACT score
|
12 weeks
|
spirometry
Time Frame: 12 weeks
|
Lung function by spirometry
|
12 weeks
|
forced oscillation
Time Frame: 12 weeks
|
Lung function by spirometry
|
12 weeks
|
FeNO
Time Frame: 12 weeks
|
Airway eosinophilic inflammation by FeNO
|
12 weeks
|
peripheral eosinophil count
Time Frame: 12 weeks
|
Allergic inflammation by peripheral eosinophil count
|
12 weeks
|
IgE
Time Frame: 12 weeks
|
Allergic inflammation by peripheral eosinophil count
|
12 weeks
|
HSPA5 (GRP78)
Time Frame: 12 weeks
|
Markers of ER stress in nasal epithelium - HSPA5 (GRP78)
|
12 weeks
|
DDIT (CHOP)
Time Frame: 12 weeks
|
Markers of ER stress in nasal epithelium - DDIT (CHOP)
|
12 weeks
|
PDIA3
Time Frame: 12 weeks
|
Markers of ER stress in nasal epithelium - PDIA3
|
12 weeks
|
XBP1
Time Frame: 12 weeks
|
Markers of ER stress in nasal epithelium - XBP1
|
12 weeks
|
serum periostin
Time Frame: 12 weeks
|
Allergic inflammation by serum periostin
|
12 weeks
|
CCL-20
Time Frame: 12 weeks
|
Allergic inflammation by CCL-20
|
12 weeks
|
IL-4
Time Frame: 12 weeks
|
Allergic inflammation by IL-4
|
12 weeks
|
IL-5
Time Frame: 12 weeks
|
Allergic inflammation by IL-5
|
12 weeks
|
IL-13
Time Frame: 12 weeks
|
Allergic inflammation by IL-13
|
12 weeks
|
IL-17A
Time Frame: 12 weeks
|
Allergic inflammation by IL-17A
|
12 weeks
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Immune System Diseases
- Lung Diseases
- Hypersensitivity, Immediate
- Bronchial Diseases
- Lung Diseases, Obstructive
- Respiratory Hypersensitivity
- Hypersensitivity
- Asthma
- Anti-Infective Agents
- Antiviral Agents
- Gastrointestinal Agents
- Cholagogues and Choleretics
- Ursodoxicoltaurine
Other Study ID Numbers
- UVermont
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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