Purpose

After HIV/AIDS, tuberculosis (TB) remains the second leading cause of death due to an infectious disease globally. Retrospective studies from many countries, including the United States and South Africa, have consistently reported that in addition to having a higher burden of TB disease, patients with problem alcohol use have worse TB treatment outcomes. This prospective study will attempt to clarify both behavioral and biologic causal mechanisms underlying the deleterious effects of problem alcohol use on TB treatment response.

Conditions

Eligibility

Eligible Ages
Over 15 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. at least 15 years old 2. initiating TB treatment in South Africa 3. expect to remain in the local area for the next 2 years 4. agree to comply with all study requirements, including provision of contact information and attendance at all study appointments 5. 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

  1. they have multidrug-resistant (MDR) TB (RIF resistance will be known at screening from Xpert MTB/RIF) 2. they have a contra-indication to start on standard 4-drug therapy 3. they are pregnant at study enrollment 4. they are HIV seropositive for aim 2 only

Study Design

Phase
N/A
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Supportive Care
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Other
DOT Adherence Monitoring
Daily adherence monitoring by study-employed directly observed therapy (DOT) worker on weekdays throughout the course of TB therapy
  • Behavioral: DOT Adherence Monitoring
    Study participants will meet with a study-employed DOT worker daily during weekdays throughout the course of their TB treatment

More Details

Status
Enrolling by invitation
Sponsor
Boston Medical Center

Study Contact

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. 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.