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Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) (ADEPTT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03302299
Recruitment Status : Completed
First Posted : October 5, 2017
Last Update Posted : June 10, 2021
Sponsor:
Collaborators:
Boston University
Boston Medical Center
Mbarara University of Science and Technology
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
The Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) will examine the safety and tolerability of, and adherence to, 6 months of daily INH (6H) in 300 TB and HIV-infected persons (200 drinkers and 100 non-drinkers) in Uganda. The first aim is to evaluate the safety and tolerability of 6H overall and by level of alcohol use. The second aim is to estimate adherence and compare adherence by level of alcohol use and at 3 and 6 months. Self-reported measures of alcohol use will be augmented by phosphatidylethanol (PEth), an established biomarker of alcohol use. Objective measures of adherence will include electronic pill bottle monitoring and a novel measure of INH exposure, INH concentration in hair. The study will actively monitor for hepatotoxicity using the U.S. standard of care for TB preventive therapy for heavy drinkers and discontinue if any Grade 3/4 toxicities are detected. The investigators will use the safety, tolerability, and adherence results, together with the known efficacy and mortality benefit of TB preventive therapy in HIV-infected persons in SSA, and an established decision analytic model of TB preventive therapy to conduct the third aim: to determine whether the benefits of TB preventive therapy outweigh the toxicity risks for HIV-infected drinkers in resource limited settings. The study will additionally follow the cohort every 6 months after completing INH to monitor drinking and the development of active TB.

Condition or disease Intervention/treatment Phase
Tuberculosis HIV/AIDS Alcohol Abuse Drug: Isoniazid 300 Mg ORAL TABLET Drug: Pyridoxine 25 Mg Oral Tablet Phase 4

Detailed Description:

Tuberculosis (TB) is the leading cause of mortality in persons with HIV worldwide, accounting for 20-33% of HIV-related deaths, and is a high-priority area of research in HIV/AIDS by the NIH. TB preventive therapy decreases both all-cause mortality and active TB in persons with HIV by 30-50% above and beyond the benefits of antiretroviral therapy (ART) alone. Based on these findings, the World Health Organization (WHO) recommends isoniazid (INH) preventive therapy (IPT) for all persons with HIV in resource constrained settings. However, the WHO warns against the use of IPT in persons with "regular and heavy alcohol use." This exclusion stems from concern for increased hepatotoxicity in heavy drinkers in settings where liver enzymes are not routinely monitored. Heavy drinking in persons with HIV is very common, approximately 25%, in sub-Saharan Africa (SSA). Heavy drinking increases the risk for active TB at least threefold; thus, HIV-infected alcohol users should be prioritized for TB prevention. However, no studies have systematically assessed the safety of TB preventive therapy in heavy drinkers with or without HIV infection. It is critical to examine the safety and tolerability of TB preventive therapy for HIV-infected drinkers, given the high rates of HIV, TB infection, and alcohol comorbidities worldwide. While the risk of toxicity exists, the risk of TB disease could outweigh the toxicity harms. Thus, it is also crucial to determine whether the mortality benefits outweigh the toxicity risks for this significant portion of the HIV-infected population.

In addition, TB preventive therapy is only effective if taken consistently for the full course. Alcohol use is an established risk factor for decreased ART pill taking and active TB treatment discontinuation. Whether HIV-infected drinkers on ART can be adherent to TB preventive therapy is not known. Therefore it is essential to determine the level of adherence to TB preventive therapy by HIV-infected drinkers on ART, thus this study aims to examine adherence to TB preventative therapy as well.

This is a study to examine 6 months of daily INH (6H) among N=300 persons co-infected with HIV and TB. The aims of the study are:

Aim 1: To examine the safety and tolerability of 6H in HIV/TB co-infected drinkers, measured by hepatotoxicity and treatment discontinuation rates. The main aim is to estimate safety and tolerability overall among drinkers (primary) and by level of drinking (secondary).

Aim 2: To determine the level of TB preventive therapy adherence overall among drinkers and by level of drinking, and at 3 and 6 months. The main goal of this aim is to estimate adherence overall among drinkers (primary). Secondarily the investigators will estimate adherence by level of drinking (heavy, current but not heavy drinkers, and non-drinkers) and compare adherence across drinking levels. The investigators hypothesize that adherence will be highest among the non-drinkers.

Aim 3: To determine whether the benefits of providing TB preventive therapy to HIV-infected drinkers in resource-limited settings outweigh the risks compared to no treatment. The investigators hypothesize that providing TB preventive therapy will result in longer life expectancy and quality-adjusted life expectancy than not providing TB preventive therapy (current standard of care).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 302 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: URBAN ARCH (3/5) Uganda Cohort TB Preventive Therapy for HIV-infected Alcohol Users in Uganda: an Evaluation of Safety Tolerability and Adherence
Actual Study Start Date : April 7, 2017
Actual Primary Completion Date : April 1, 2021
Actual Study Completion Date : April 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Isoniazid & pyridoxine
Isoniazid 300 mg oral tablet: 300 mg daily by mouth for 6 months. Pyridoxine 25 mg oral tablet: 25mg daily by mouth for 6 months.
Drug: Isoniazid 300 Mg ORAL TABLET
The study intervention will include a single arm given (1) 6H: 300 mg INH daily by mouth for 6 months.
Other Name: INH

Drug: Pyridoxine 25 Mg Oral Tablet
All participants will also receive 25 mg pyridoxine (vitamin B-6) daily by mouth for 6 months for the treatment duration to reduce the risk of INH-induced peripheral neuropathy.
Other Name: Vitamin B6




Primary Outcome Measures :
  1. Grade 3/4 hepatotoxicity [ Time Frame: Hepatotoxicity occurring during the six month course (180 pills) of INH (which may be taken over a maximum of 9 months) ]
    Safety will be assessed by the occurrence of a Grade 3/4 hepatotoxicity at any time during the assigned treatment period.


Secondary Outcome Measures :
  1. Treatment discontinuation [ Time Frame: Treatment discontinuation occuring during the six month course (180 pills) of INH (which may be taken over a maximum of 9 months) ]
    Lack of tolerability will be defined as any treatment discontinuation prior to completion of the prescribed course (6 months of INH over a maximum period of 9 months) due to side effects or ALT/AST elevations.

  2. INH medication adherence by Electronic Medication Monitoring [ Time Frame: Adherence will be measured over the 6 months on INH or until INH discontinuation (whichever is shorter) ]
    EMM adherence will be defined as the number of pill bottle openings (no more than 1 per day counted) divided by the number of prescribed doses over the study period openings (no more than 1 per day counted) divided by the number of prescribed doses over the study period.

  3. Self-reported INH medication adherence by visual analog scale [ Time Frame: Self-reported INH medication adherence via VAS will be measured 3- and 6- months after starting INH ]
    The visual analog scale (VAS) asks the patient to identify their past month percent adherence on a visual scale that ranges from 0 to 100%. The VAS is administered at 3- and 6-month interviews. The average of the two measures for this outcome will be used for analysis.

  4. Self-reported INH medication adherence by the Self Rating Single Item (SRSI) scale [ Time Frame: Self-reported INH medication adherence via SRSI will be measured 3- and 6- months after starting INH ]
    The study will administer the Self Rating Single Item (SRSI) adherence scale, which asks participants to rate their ability to take their medications as prescribed over the past month at the 3- and 6-month interview. The lower score of the 2 surveys administered will be used.


Other Outcome Measures:
  1. INH concentration in hair [ Time Frame: Measured at 3- and 6- months after INH initiation ]
    INH concentration in hair (ng/mg) will be measured at 3- and 6- months during INH therapy. Average concentration will be used.

  2. Liver injury [ Time Frame: Study screening visit ]
    ALT or AST elevations (>2x the upper limit of normal) at study screening

  3. Latent tuberculosis [ Time Frame: Study screening visit ]
    Latent tuberculosis assessed at screening via tuberculin skin testing



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age > 18 years old
  2. Patient of the MRRH ISS Clinic
  3. HIV-infected
  4. Consume alcohol (self-reported consumption in the prior 3 months) (2/3) OR prior year non-drinker (1/3)
  5. Live within 2 hours of travel time to the ISS Clinic
  6. Fluent in either Runyankole or English
  7. No ALT/AST elevations (< = 2X ULN) confirmed by testing
  8. On ART for at least 6 months
  9. No history of active TB, TB treatment, or TB preventive therapy
  10. No probable current active TB as determined by symptom screening and followed by chest X-ray and Xpert MTB/RIF (if symptomatic)
  11. Positive TST results confirmed by testing

Exclusion Criteria:

  1. Plans to move out of the catchment area within 6 months
  2. Probable TB via symptom screen and subsequent assessments
  3. History or current or past active TB, TB treatment, or TB preventive therapy
  4. ALT or AST >2x ULN
  5. Pregnant women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03302299


Locations
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Uganda
Mbarara University of Science and Technology/Mbarara Regional Referral Hospital
Mbarara, Uganda
Sponsors and Collaborators
University of California, San Francisco
Boston University
Boston Medical Center
Mbarara University of Science and Technology
Investigators
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Principal Investigator: Judith A Hahn, PhD, MA University of California, San Francisco
  Study Documents (Full-Text)

Documents provided by University of California, San Francisco:
Additional Information:
Publications:
TEMPRANO ANRS 12136 Study Group, Danel C, Moh R, Gabillard D, Badje A, Le Carrou J, Ouassa T, Ouattara E, Anzian A, Ntakpé JB, Minga A, Kouame GM, Bouhoussou F, Emieme A, Kouamé A, Inwoley A, Toni TD, Ahiboh H, Kabran M, Rabe C, Sidibé B, Nzunetu G, Konan R, Gnokoro J, Gouesse P, Messou E, Dohoun L, Kamagate S, Yao A, Amon S, Kouame AB, Koua A, Kouamé E, Ndri Y, Ba-Gomis O, Daligou M, Ackoundzé S, Hawerlander D, Ani A, Dembélé F, Koné F, Guéhi C, Kanga C, Koule S, Séri J, Oyebi M, Mbakop N, Makaila O, Babatunde C, Babatounde N, Bleoué G, Tchoutedjem M, Kouadio AC, Sena G, Yededji SY, Assi R, Bakayoko A, Mahassadi A, Attia A, Oussou A, Mobio M, Bamba D, Koman M, Horo A, Deschamps N, Chenal H, Sassan-Morokro M, Konate S, Aka K, Aoussi E, Journot V, Nchot C, Karcher S, Chaix ML, Rouzioux C, Sow PS, Perronne C, Girard PM, Menan H, Bissagnene E, Kadio A, Ettiegne-Traore V, Moh-Semdé C, Kouame A, Massumbuko JM, Chêne G, Dosso M, Domoua SK, N'Dri-Yoman T, Salamon R, Eholié SP, Anglaret X. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa. N Engl J Med. 2015 Aug 27;373(9):808-22. doi: 10.1056/NEJMoa1507198. Epub 2015 Jul 20.
Getahun H, Matteelli A, Abubakar I, Aziz MA, Baddeley A, Barreira D, Den Boon S, Borroto Gutierrez SM, Bruchfeld J, Burhan E, Cavalcante S, Cedillos R, Chaisson R, Chee CB, Chesire L, Corbett E, Dara M, Denholm J, de Vries G, Falzon D, Ford N, Gale-Rowe M, Gilpin C, Girardi E, Go UY, Govindasamy D, D Grant A, Grzemska M, Harris R, Horsburgh CR Jr, Ismayilov A, Jaramillo E, Kik S, Kranzer K, Lienhardt C, LoBue P, Lönnroth K, Marks G, Menzies D, Migliori GB, Mosca D, Mukadi YD, Mwinga A, Nelson L, Nishikiori N, Oordt-Speets A, Rangaka MX, Reis A, Rotz L, Sandgren A, Sañé Schepisi M, Schünemann HJ, Sharma SK, Sotgiu G, Stagg HR, Sterling TR, Tayeb T, Uplekar M, van der Werf MJ, Vandevelde W, van Kessel F, van't Hoog A, Varma JK, Vezhnina N, Voniatis C, Vonk Noordegraaf-Schouten M, Weil D, Weyer K, Wilkinson RJ, Yoshiyama T, Zellweger JP, Raviglione M. Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries. Eur Respir J. 2015 Dec;46(6):1563-76. doi: 10.1183/13993003.01245-2015. Epub 2015 Sep 24. Review.

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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03302299    
Other Study ID Numbers: 2U01AA020776-06 ( U.S. NIH Grant/Contract )
First Posted: October 5, 2017    Key Record Dates
Last Update Posted: June 10, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The investigators will make de-identified data available to investigators with relevant and well-articulated research plans, after the main study analyses have been conducted. No personal identifiers will be shared, and nor identifiers that could be linked back to the original study ID. In addition, some journals require de-identified data to be posted for public access.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of California, San Francisco:
Adherence
Hepatotoxicity
Phosphatidtylethanol
Additional relevant MeSH terms:
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Tuberculosis
Alcoholism
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Pyridoxine
Vitamin B 6
Isoniazid
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Vitamin B Complex
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents