- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02840877
The Impact of Alcohol Consumption on Tuberculosis Treatment Outcomes
Study Overview
Status
Intervention / Treatment
Detailed Description
A major knowledge gap is the degree to which poor treatment outcomes in alcohol-abusing patients are due to noncompliance alone. Problem alcohol use impacts on retention in care and adherence to daily TB treatment. Poor medication adherence and increased default from TB care have been documented for patients consuming alcohol regularly in several countries. Yet there has been no research to identify reasons (beyond adherence) for these poorer outcomes among patients with problem alcohol use. A key barrier to understanding the persistent biologic effect of alcohol on TB disease is inadequate data on adherence, including detailed data on daily adherence (or number of missed doses of medication). Research combining better approaches to alcohol ascertainment and adherence monitoring is needed to advance understanding of the pathways by which alcohol use and TB disease interact.
Aim 1: To (i) examine the associations between problem alcohol use and TB treatment outcomes, and (ii) demonstrate that these associations persist independent of adherence to TB treatment.
Aim 2: To evaluate the effect of problem alcohol use on the pharmacokinetics (PK)/pharmacodynamics (PD) of TB drugs.
Aim 3: We will use existing samples and data and continue to collect samples and data to (A) evaluate Mtb diversity in host, its dynamics overtime and in a specific set of drug resistance, drug tolerance, virulence and immune regulator genes, for evidence of directional and diversifying selection. We will (B) also evaluate how Mtb diversity and genes under selection associate with time-to culture conversion (three consecutive weeks of negative growth) and negative treatment outcomes, adherence, HIV, diabetes mellitus (DM), and substance use. We will (C) leverage MIC and sequence data from TRUST. We will combine these with a large public Mtb MIC and WGS dataset enriched for high-level antibiotic resistance generated by studies that include the NIAID funded Harvard TB Centers of Excellence for Translational Research (CETR). We will train an in silico MIC predictor and probe interactions between mutations and the Mtb lineage on a genome-wide scale. The current TRUST investigators, as well as Dr. Maha Farhat, Harvard Medical School will oversee this aim.
Aim 4: A) To compare rates of dysglycemia (both hyperglycemia and hypoglycemia) in people living with HIV (PLWH) and HIV-uninfected persons receiving TB treatment in order to assess changes in blood glucose levels from study enrollment by HIV status and how alcohol use mediates the relationship; and B) to assess the role stress, inflammation and alcohol consumption play in relation to blood sugar levels in PLWH and HIV-uninfected individuals and to assess epigenetic modifications at DNA sites known to be involved in TB risk and neutrophil, monocyte, T and B cell function.
Culture-positive, pulmonary TB patients will be recruited in Worcester, South Africa, and followed over an 18-month period. Patients will complete an interviewer-administered questionnaire on their alcohol use and other health-related behaviors, and their recent alcohol use will be confirmed using a biomarker (phosphatidylethanol). Chest radiographs, sputum smears and culture, and blood samples will be collected to compare the biology of treatment response in patients with and without problem alcohol use. During the 6-month treatment period, smart mobile-phone technology will be used to document daily drug adherence by trained community workers. Serial measures of alcohol intake and serial sputa isolates will be collected to assess treatment response and TB drug side effects will be recorded. In addition, intensive PK/PD studies of isoniazid, rifampin, ethambutol, and pyrazinamide will be performed in 200 HIV-seronegative patients. The full cohort will be followed for 12 months post-treatment to examine long-term TB outcomes, including relapse and death.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Western Cape Province
-
Worcester, Western Cape Province, South Africa
- Worcester Community Day Centre
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- at least 15 years old
- initiating TB treatment in South Africa
- expect to remain in the local area for the next 2 years
- agree to comply with all study requirements, including provision of contact information and attendance at all study appointments
- provide written, informed consent to participate in the study if ≥18 years of age or written assent and parental consent if <18 years.
Exclusion Criteria:
- they have multidrug-resistant (MDR) TB (RIF resistance will be known at screening from Xpert MTB/RIF)
- they have a contra-indication to start on standard 4-drug therapy
- they are pregnant at study enrollment
- they are HIV seropositive for aim 2 only
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: DOT Adherence Monitoring
Daily adherence monitoring by study-employed directly observed therapy (DOT) worker on weekdays throughout the course of TB therapy
|
Study participants will meet with a study-employed DOT worker daily during weekdays throughout the course of their TB treatment
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Culture Conversion
Time Frame: 12 weeks
|
Time to sterilization/culture conversion during the first twelve weeks of treatment in patients with problem alcohol use compared to those without
|
12 weeks
|
Cmax
Time Frame: 4 weeks
|
Peak concentrations (Cmax) of isoniazid, rifampin, pyrazinamide, and ethambutol in patients with problem alcohol use compared to those without
|
4 weeks
|
Area Under Curve (AUC)
Time Frame: 4 weeks
|
Individual patient steady state 24-hour area under curve (AUC) of isoniazid, rifampin, pyrazinamide, and ethambutol
|
4 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Poor Treatment Outcome
Time Frame: 18 months
|
Risk of poor final TB outcomes (defined as treatment failure, death, or relapse) in patients with problem alcohol use compared to those without
|
18 months
|
Side Effects to TB Drugs
Time Frame: 6 months
|
Percentage of patients who develop side effects to the TB drugs in patients with problem alcohol use compared to those without
|
6 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Karen Jacobson, MD MPH, Boston Medical Center, Department of Medicine
Publications and helpful links
General Publications
- Ragan EJ, Gill CJ, Banos M, Bouton TC, Rooney J, Horsburgh CR, Warren RM, Myers B, Jacobson KR. Directly Observed Therapy to Measure Adherence to Tuberculosis Medication in Observational Research: Protocol for a Prospective Cohort Study. JMIR Res Protoc. 2021 Jun 16;10(6):e24510. doi: 10.2196/24510.
- Myers B, Bouton TC, Ragan EJ, White LF, McIlleron H, Theron D, Parry CDH, Horsburgh CR, Warren RM, Jacobson KR. Impact of alcohol consumption on tuberculosis treatment outcomes: a prospective longitudinal cohort study protocol. BMC Infect Dis. 2018 Sep 29;18(1):488. doi: 10.1186/s12879-018-3396-y.
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 (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- H-34970
- 1R01AI119037-01A1 (U.S. NIH Grant/Contract)
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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