The Impact of Alcohol Consumption on Tuberculosis Treatment Outcomes

Sponsor
Boston Medical Center (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02840877
Collaborator
Medical Research Council, South Africa (Other), Boston University (Other), University of Cape Town (Other), National Institute of Allergy and Infectious Diseases (NIAID) (NIH), University of Stellenbosch (Other)
304
1
1
69.5
4.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Behavioral: DOT Adherence Monitoring
N/A

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
304 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Supportive Care
Official Title:
The Impact of Alcohol Consumption on Tuberculosis Treatment Outcomes
Actual Study Start Date :
May 16, 2017
Anticipated Primary Completion Date :
Mar 1, 2023
Anticipated Study Completion Date :
Mar 1, 2023

Arms and Interventions

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

Behavioral: DOT Adherence Monitoring
Study participants will meet with a study-employed DOT worker daily during weekdays throughout the course of their TB treatment

Outcome Measures

Primary Outcome Measures

  1. Time to culture conversion [12 weeks]

    Time to sterilization/culture conversion during the first twelve weeks of treatment in patients with problem alcohol use compared to those without

  2. Cmax and AUC [4 weeks]

    Peak concentrations (Cmax) and individual patient steady state 24-hour area under curve (AUC) of isoniazid, rifampin, pyrazinamide, and ethambutol in patients with problem alcohol use compared to those without

Secondary Outcome Measures

  1. Poor treatment outcome [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

  2. Side effects to TB drugs [6 months]

    Percentage of patients who develop side effects to the TB drugs in patients with problem alcohol use compared to those without

Eligibility Criteria

Criteria

Ages Eligible for Study:
15 Years and Older
Sexes Eligible for Study:
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Worcester Community Day Centre Worcester Western Cape Province South Africa

Sponsors and Collaborators

  • Boston Medical Center
  • Medical Research Council, South Africa
  • Boston University
  • University of Cape Town
  • National Institute of Allergy and Infectious Diseases (NIAID)
  • University of Stellenbosch

Investigators

  • Principal Investigator: Karen Jacobson, MD MPH, Boston Medical Center, Department of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Boston Medical Center
ClinicalTrials.gov Identifier:
NCT02840877
Other Study ID Numbers:
  • H-34970
  • 1R01AI119037-01A1
First Posted:
Jul 21, 2016
Last Update Posted:
Jun 30, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Boston Medical Center
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 30, 2022