TuberculosisNCT01301144
Oral Urea Breath Testing for Diagnosis and Treatment Response in Pulmonary Tuberculosis
An observational study of Tuberculosis and Urea Breath Test, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Mali.
Trial summary
Background: Tuberculosis is a disease of the lungs caused by the bacteria Mycobacterium tuberculosis (M. tuberculosis). The most popular and least expensive tool used to detect the presence of the tuberculosis bacteria is called sputum smears, which is a lab test used to look for bacteria in the sputum via a… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis, Urea Breath Test
- How many people
- 113 participants
- Where
- 1 siteMali
- Study dates
- 13 Feb 2011to 30 Mar 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals (greater than or equal to18 years of age) are eligible to enter the study, if they meet the following criteria:
- Healthy volunteers (primary study group) or have a diagnosis of TB (as diagnosed by sputum smear tests; all three study groups).
- Willingness and ability to give informed consent.
- Willingness to undergo HIV testing.
- Willingness to have samples stored for future studies.
Who cannot join
- Subjects are not eligible to enter the study, if they meet any of the following criteria:
- HIV infection.
- Past history of TB (Healthy volunteers only)
- Pregnancy and lactation
- Known history of diabetes
- Use of Tuberculosis treatment proton pump inhibitor treatments or use of bismuth containing preparations in the last 15 days prior to study entry.
Show all 9Show fewer
- History of failed TB treatment
- Known allergy to aspirin or hypersensitivity to mannitol, citric acid or aspartame such as a clinical history suggestive of aminoacidurias.
- Any known medical disorder or other circumstance, which in the opinion of the PI, might make the participation of the individual unsafe or difficult. The reason for exclusion will be documented in the screening log.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Sensitivity and Specificity of Oral Urea Breath Testing for Presumptive Diagnosis and Treatment Response in Pulmonary Tuberculosis in Bamako, Mali
Background:
- Tuberculosis is a disease of the lungs caused by the bacteria Mycobacterium tuberculosis (M. tuberculosis). The most popular and least expensive tool used to detect the presence of the tuberculosis bacteria is called sputum smears, which is a lab test used to look for bacteria in the sputum via a microscope. However, the test s results are not always accurate, and the test cannot determine if the bacteria will be resistant to standard tuberculosis treatments. The most sensitive test currently available is called sputum culture, in which a sputum sample is used to check for the growth of tuberculosis bacteria. However, this test takes at least a month to produce accurate results, and requires expensive equipment that is not available in many countries where M. tuberculosis is found.
- The urea breath test (UBT) has been used to detect infection with Helicobacter pylori, a bacteria associated with stomach ulcers, by testing individual breath samples. Researchers are interested in determining whether breath samples can also be used to detect the presence of M. tuberculosis in the lungs of subjects with tuberculosis, and to see if tuberculosis treatments are successful.
Read more
Objectives:
- To assess the sensitivity and specificity of urea breath testing in the diagnosis and treatment response of pulmonary tuberculosis.
Eligibility:
- Individuals at least 18 years of age who either have been diagnosed with tuberculosis or are healthy volunteers with no past history of tuberculosis.
- The study will be conducted in Bamako, Mali.
Design:
- This study will involve three groups: two pilot groups of individuals who have already been diagnosed with tuberculosis, and a primary study group of both healthy volunteers and individuals who have been diagnosed with tuberculosis.
- Participants will be screened with a physical examination and medical history, as well as blood, sputum, stool, and urine samples.
- First pilot group (one visit):
- Participants should not eat, drink, or smoke for at least 1 hour prior to the UBT test.
- Participants will provide a baseline exhaled air sample, and then will receive the UBT test, which involves a dose of Pranactin -Citric dissolved in water. Additional exhaled air samples will be collected at eight time points (10, 20, 45, 60, 90, 120, 180, and 240 minutes after the dose).
- Second pilot group (one or two visits):
- Participants should not eat, drink, or smoke for at least 1 hour prior to the UBT test.
- Participants will provide a baseline exhaled air sample, and then will receive the UBT test. Half of the participants will receive a dose of bismuth (Pepto-Bismol) prior to collection of air samples to see how this affects the results of the UBT test. Additional exhaled air samples will be collected at three time points specified by the study researchers.
- On the following day, participants will return for a second visit to provide three more exhaled air samples.
- Primary study group (five visits for participants with tuberculosis, two visits for healthy volunteers):
- All participants will have two visits, following the procedures given for the second pilot group. Half will receive a dose of bismuth prior to collection of air samples.
- Participants with tuberculosis will have three additional visits (days 6, 10, and 16 following the first study visit) to provide additional sputum and exhaled air samples to monitor the progress of tuberculosis treatment.
Read the detailed description
Tuberculosis (TB) is a disease that affects the population worldwide, with 9 million people being infected every year. It is associated with high rates of mortality and morbidity. Reports show that a person dies from tuberculosis every 20 seconds worldwide. Current diagnostic techniques are either inadequate at detecting TB cases with precision, or they are time consuming, expensive, and require laboratory equipment not available in developing countries, where the disease is endemic. Furthermore, rates of multi-drug-resistant (MDR) TB are estimated to be over 5 percent of the incident cases globally and extremely drug-resistant (XDR) TB rates are on the rise. These statistics highlight the need for new and improved diagnostic tools for TB, as well as biomarkers that can quickly detect drug resistant organisms or treatment failures to first-line antimicrobials.
Urea breath test (UBT) has been approved by the Food and Drug Administration (FDA) for the detection of Helicobacter pylori. It is known that H. pylori possesses a urease enzyme that degrades urea in the stomach, producing carbon dioxide (CO (2)), which is then exhaled and can be detected in the lungs. Mycobacterium tuberculosis like H. pylori possesses a urease enzyme, which converts urea to carbon dioxide and ammonia. In a preclinical study, Jassal and colleagues demonstrated that TB-infected rabbits convert [(13)C]-labeled urea into [(13)C]-carbon dioxide ((13)CO(2)) in a matter of minutes. The (13)CO(2) in exhaled breath could be rapidly detected with an isotopic ratio mass spectrometer or a small ultraviolet (UV) absorbance spectrometer.
The primary objective of the current study is to evaluate the sensitivity and specificity of UBT in the diagnosis and treatment response of pulmonary TB. Secondary objectives are to assess the specificity of UBT for M. tuberculosis (UBT-TB) diagnosis in volunteers with and without H. pylori infection, examine the benefit of bismuth to make UBT-TB more specific for M. tuberculosis, and evaluate the correlation of the labeled (13)CO(2) signal with sputum colony forming unit (CFU) counts and the lower limit of signal detection versus CFU counts.
- Conditions
- Tuberculosis, Urea Breath Test
- Keywords
- Tuberculosis, Urea Breath Test
- Medical subject headings
- Tuberculosis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2011 (estimated)
- Study start13 Feb 2011
- Study completion30 Mar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Observational
- Time perspective
- Prospective
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sophia B Siddiqui, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01301144
- Sponsor's protocol ID
- 999911106
- Other IDs
- 11-I-N106
- Status last verified
- 30 Mar 2016
- First submitted
- 18 Feb 2011
- Last updated
- 5 Apr 2018
- Results posted
- No
Publications
Jassal M, Bishai WR. Extensively drug-resistant tuberculosis. Lancet Infect Dis. 2009 Jan;9(1):19-30. doi: 10.1016/S1473-3099(08)70260-3. Epub 2008 Nov 5.
PubMed 18990610Jassal MS, Nedeltchev GG, Lee JH, Choi SW, Atudorei V, Sharp ZD, Deretic V, Timmins GS, Bishai WR. 13[C]-urea breath test as a novel point-of-care biomarker for tuberculosis treatment and diagnosis. PLoS One. 2010 Aug 27;5(8):e12451. doi: 10.1371/journal.pone.0012451.
PubMed 20805989Bell GD, Weil J, Harrison G, Morden A, Jones PH, Gant PW, Trowell JE, Yoong AK, Daneshmend TK, Logan RF. 14C-urea breath analysis, a non-invasive test for Campylobacter pylori in the stomach. Lancet. 1987 Jun 13;1(8546):1367-8. doi: 10.1016/s0140-6736(87)90664-7. No abstract available.
PubMed 2884468
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sensitivity and Specificity of Oral Urea Breath Testing for Presumptive Diagnosis and Treatment Response in Pulmonary Tuberculosis in Bamako, Mali
- ClinicalTrials.gov ID
- NCT01301144
- Acronym / sponsor ID
- 999911106
- Conditions
- Tuberculosis, Urea Breath Test
- Keywords
- Tuberculosis, Urea Breath Test
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 13 Feb 2011
- Study completion
- 30 Mar 2016
- First posted
- 23 Feb 2011 (estimated)
- 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.
Background:
- Tuberculosis is a disease of the lungs caused by the bacteria Mycobacterium tuberculosis (M. tuberculosis). The most popular and least expensive tool used to detect the presence of the tuberculosis bacteria is called sputum smears, which is a lab test used to look for bacteria in the sputum via a microscope. However, the test s results are not always accurate, and the test cannot determine if the bacteria will be resistant to standard tuberculosis treatments. The most sensitive test currently available is called sputum culture, in which a sputum sample is used to check for the growth of tuberculosis bacteria. However, this test takes at least a month to produce accurate results, and requires expensive equipment that is not available in many countries where M. tuberculosis is found.
- The urea breath test (UBT) has been used to detect infection with Helicobacter pylori, a bacteria associated with stomach ulcers, by testing individual breath samples. Researchers are interested in determining whether breath samples can also be used to detect the presence of M. tuberculosis in the lungs of subjects with tuberculosis, and to see if tuberculosis treatments are successful.
Objectives:
- To assess the sensitivity and specificity of urea breath testing in the diagnosis and treatment response of pulmonary tuberculosis.
Eligibility:
- Individuals at least 18 years of age who either have been diagnosed with tuberculosis or are healthy volunteers with no past history of tuberculosis.
- The study will be conducted in Bamako, Mali.
Design:
- This study will involve three groups: two pilot groups of individuals who have already been diagnosed with tuberculosis, and a primary study group of both healthy volunteers and individuals who have been diagnosed with tuberculosis.
- Participants will be screened with a physical examination and medical history, as well as blood, sputum, stool, and urine samples.
- First pilot group (one visit):
- Participants should not eat, drink, or smoke for at least 1 hour prior to the UBT test.
- Participants will provide a baseline exhaled air sample, and then will receive the UBT test, which involves a dose of Pranactin -Citric dissolved in water. Additional exhaled air samples will be collected at eight time points (10, 20, 45, 60, 90, 120, 180, and 240 minutes after the dose).
- Second pilot group (one or two visits):
- Participants should not eat, drink, or smoke for at least 1 hour prior to the UBT test.
- Participants will provide a baseline exhaled air sample, and then will receive the UBT test. Half of the participants will receive a dose of bismuth (Pepto-Bismol) prior to collection of air samples to see how this affects the results of the UBT test. Additional exhaled air samples will be collected at three time points specified by the study researchers.
- On the following day, participants will return for a second visit to provide three more exhaled air samples.
- Primary study group (five visits for participants with tuberculosis, two visits for healthy volunteers):
- All participants will have two visits, following the procedures given for the second pilot group. Half will receive a dose of bismuth prior to collection of air samples.
- Participants with tuberculosis will have three additional visits (days 6, 10, and 16 following the first study visit) to provide additional sputum and exhaled air samples to monitor the progress of tuberculosis treatment.
Detailed description
Tuberculosis (TB) is a disease that affects the population worldwide, with 9 million people being infected every year. It is associated with high rates of mortality and morbidity. Reports show that a person dies from tuberculosis every 20 seconds worldwide. Current diagnostic techniques are either inadequate at detecting TB cases with precision, or they are time consuming, expensive, and require laboratory equipment not available in developing countries, where the disease is endemic. Furthermore, rates of multi-drug-resistant (MDR) TB are estimated to be over 5 percent of the incident cases globally and extremely drug-resistant (XDR) TB rates are on the rise. These statistics highlight the need for new and improved diagnostic tools for TB, as well as biomarkers that can quickly detect drug resistant organisms or treatment failures to first-line antimicrobials.
Urea breath test (UBT) has been approved by the Food and Drug Administration (FDA) for the detection of Helicobacter pylori. It is known that H. pylori possesses a urease enzyme that degrades urea in the stomach, producing carbon dioxide (CO (2)), which is then exhaled and can be detected in the lungs. Mycobacterium tuberculosis like H. pylori possesses a urease enzyme, which converts urea to carbon dioxide and ammonia. In a preclinical study, Jassal and colleagues demonstrated that TB-infected rabbits convert [(13)C]-labeled urea into [(13)C]-carbon dioxide ((13)CO(2)) in a matter of minutes. The (13)CO(2) in exhaled breath could be rapidly detected with an isotopic ratio mass spectrometer or a small ultraviolet (UV) absorbance spectrometer.
The primary objective of the current study is to evaluate the sensitivity and specificity of UBT in the diagnosis and treatment response of pulmonary TB. Secondary objectives are to assess the specificity of UBT for M. tuberculosis (UBT-TB) diagnosis in volunteers with and without H. pylori infection, examine the benefit of bismuth to make UBT-TB more specific for M. tuberculosis, and evaluate the correlation of the labeled (13)CO(2) signal with sputum colony forming unit (CFU) counts and the lower limit of signal detection versus CFU counts.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Individuals (greater than or equal to18 years of age) are eligible to enter the study, if they meet the following criteria:
- Healthy volunteers (primary study group) or have a diagnosis of TB (as diagnosed by sputum smear tests; all three study groups).
- Willingness and ability to give informed consent.
- Willingness to undergo HIV testing.
- Willingness to have samples stored for future studies.
Key exclusion criteria (9 listed)
- HIV infection.
- Past history of TB (Healthy volunteers only)
- Pregnancy and lactation
- Known history of diabetes
- Use of Tuberculosis treatment proton pump inhibitor treatments or use of bismuth containing preparations in the last 15 days prior to study entry.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2018.
- Background: PubMed 18990610Jassal M, Bishai WR. Extensively drug-resistant tuberculosis. Lancet Infect Dis. 2009 Jan;9(1):19-30. doi: 10.1016/S1473-3099(08)70260-3. Epub 2008 Nov 5.
- Background: PubMed 20805989Jassal MS, Nedeltchev GG, Lee JH, Choi SW, Atudorei V, Sharp ZD, Deretic V, Timmins GS, Bishai WR. 13[C]-urea breath test as a novel point-of-care biomarker for tuberculosis treatment and diagnosis. PLoS One. 2010 Aug 27;5(8):e12451. doi: 10.1371/journal.pone.0012451.
- Background: PubMed 2884468Bell GD, Weil J, Harrison G, Morden A, Jones PH, Gant PW, Trowell JE, Yoong AK, Daneshmend TK, Logan RF. 14C-urea breath analysis, a non-invasive test for Campylobacter pylori in the stomach. Lancet. 1987 Jun 13;1(8546):1367-8. doi: 10.1016/s0140-6736(87)90664-7. No abstract available.
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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. This study is not recruiting at the moment.
Sophia B Siddiqui, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis and Urea Breath Test, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Mali.
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 5 inclusion and 9 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: finished, as of the sponsor's last update on 5 Apr 2018. 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 Mali. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01301144, which also lists 3 linked publications.
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 5 Apr 2018.