DNA Sequencing of MDR TB in Eastern Siberia

NCT02508610 | Unknown

• 1 other identifier: 17142
• Study Type: observational
• Target: 630
• Locations: 1 country
• Sites: 1

Brief Summary

This is protocol is generated in response to the exploratory R21 from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) for US-Russia collaborative research in HIV/tuberculosis (TB). Given the exploratory focus of the protocol and the short time frame of funding (2 years) we will study TB in Irkutsk, in Eastern Siberia. Irkutsk is one of the hardest-hit areas in all of the Russian Federation for drug-resistant TB and poor TB outcomes. Specifically, the investigators will examine the factors of anti-TB drug pharmacokinetics, TB drug-resistance mutations and virulent/transmissible M. tuberculosis sublineages. This foundational work will inform future diagnostic strategies and therapeutic regimens.

Conditions

Tuberculosis; HIV

Outcome Measures

Primary Outcomes (1)

• TB drug-susceptibility testing

  For subjects suspected of TB, sputum samples or other leftover sputum/blood specimens will be screened by GeneXpert and if positive, cultured for TB and the cultured specimen subjected to drug-susceptibility testing by conventional qualitative resistance and minimum inhibitory concentration (MIC), sequencing for drug-resistance mutation and spoligotyping for sublineage identification. Primary analysis will include standard sensitivity/specificity of each drug-mutation compared to conventional qualitative resistance and then median/range MIC values among isolates with/without mutation for improved discrimination.

  The participants will be followed for the duration of hospital stay, an expected average of 12 weeks.

Secondary Outcomes (4)

• The proportion of patients below the expected Cmax range

  The participants will be followed for the duration of hospital stay, an expected average of 12 weeks.

• The proportion of patients below the expected AUC range

  The participants will be followed for the duration of hospital stay, an expected average of 12 weeks.

• Correlation of Cmax with the primary outcome

  The participants will be followed for the duration of hospital stay, an expected average of 12 weeks.

• Correlation of AUC with the primary outcome

  The participants will be followed for the duration of hospital stay, an expected average of 12 weeks.

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects will be enrolled from patients attending either Irkutsk Dispensary or the affiliate referral clinic (Irkutsk AIDS Center).

You may qualify if:

• All patients suspected of TB at Irkutsk Dispensary/Irkutsk AIDS Center.
• age \>15 years

You may not qualify if:

• Pregnancy (self reported)
• Prisoner or ward of the state

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

Institute of Epidemiology & Microbiology of Scientific Center

Timiryazeva, Irkutsk Oblast, 664003, Russia

RECRUITING

Related Publications (11)

• Zhdanova S, Heysell SK, Ogarkov O, Boyarinova G, Alexeeva G, Pholwat S, Zorkaltseva E, Houpt ER, Savilov E. Primary multidrug-resistant Mycobacterium tuberculosis in 2 regions, Eastern Siberia, Russian Federation. Emerg Infect Dis. 2013 Oct;19(10):1649-52. doi: 10.3201/eid1910.121108.

  PMID: 24047678 BACKGROUND

• Peloquin CA, Nitta AT, Burman WJ, Brudney KF, Miranda-Massari JR, McGuinness ME, Berning SE, Gerena GT. Low antituberculosis drug concentrations in patients with AIDS. Ann Pharmacother. 1996 Sep;30(9):919-25. doi: 10.1177/106002809603000901.

  PMID: 8876848 BACKGROUND

• Chideya S, Winston CA, Peloquin CA, Bradford WZ, Hopewell PC, Wells CD, Reingold AL, Kenyon TA, Moeti TL, Tappero JW. Isoniazid, rifampin, ethambutol, and pyrazinamide pharmacokinetics and treatment outcomes among a predominantly HIV-infected cohort of adults with tuberculosis from Botswana. Clin Infect Dis. 2009 Jun 15;48(12):1685-94. doi: 10.1086/599040.

  PMID: 19432554 BACKGROUND

• Heysell SK, Mtabho C, Mpagama S, Mwaigwisya S, Pholwat S, Ndusilo N, Gratz J, Aarnoutse RE, Kibiki GS, Houpt ER. Plasma drug activity assay for treatment optimization in tuberculosis patients. Antimicrob Agents Chemother. 2011 Dec;55(12):5819-25. doi: 10.1128/AAC.05561-11. Epub 2011 Oct 3.

  PMID: 21968363 BACKGROUND

• Heysell SK, Moore JL, Keller SJ, Houpt ER. Therapeutic drug monitoring for slow response to tuberculosis treatment in a state control program, Virginia, USA. Emerg Infect Dis. 2010 Oct;16(10):1546-53. doi: 10.3201/eid1610.100374.

  PMID: 20875279 BACKGROUND

• Shenoi S, Heysell S, Moll A, Friedland G. Multidrug-resistant and extensively drug-resistant tuberculosis: consequences for the global HIV community. Curr Opin Infect Dis. 2009 Feb;22(1):11-7. doi: 10.1097/QCO.0b013e3283210020.

  PMID: 19532076 BACKGROUND

• Heysell SK, Houpt ER. The future of molecular diagnostics for drug-resistant tuberculosis. Expert Rev Mol Diagn. 2012 May;12(4):395-405. doi: 10.1586/erm.12.25.

  PMID: 22616704 BACKGROUND

• Bobkov A, Kazennova E, Khanina T, Bobkova M, Selimova L, Kravchenko A, Pokrovsky V, Weber J. An HIV type 1 subtype A strain of low genetic diversity continues to spread among injecting drug users in Russia: study of the new local outbreaks in Moscow and Irkutsk. AIDS Res Hum Retroviruses. 2001 Feb 10;17(3):257-61. doi: 10.1089/088922201750063188.

  PMID: 11177409 BACKGROUND

• Dymova MA, Kinsht VN, Cherednichenko AG, Khrapov EA, Svistelnik AV, Filipenko ML. Highest prevalence of the Mycobacterium tuberculosis Beijing genotype isolates in patients newly diagnosed with tuberculosis in the Novosibirsk oblast, Russian Federation. J Med Microbiol. 2011 Jul;60(Pt 7):1003-1009. doi: 10.1099/jmm.0.027995-0. Epub 2011 Mar 24.

  PMID: 21436372 BACKGROUND

• Millan-Lou MI, Alonso H, Gavin P, Hernandez-Febles M, Campos-Herrero MI, Copado R, Canas F, Kremer K, Caminero JA, Martin C, Samper S. Rapid test for identification of a highly transmissible Mycobacterium tuberculosis Beijing strain of sub-Saharan origin. J Clin Microbiol. 2012 Feb;50(2):516-8. doi: 10.1128/JCM.06314-11. Epub 2011 Nov 23.

  PMID: 22116140 BACKGROUND

• Swaminathan S, Rekha B. Pediatric tuberculosis: global overview and challenges. Clin Infect Dis. 2010 May 15;50 Suppl 3:S184-94. doi: 10.1086/651490.

  PMID: 20397947 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

We will collect and use plasma and sputum specimens. For a minority of subjects, leftover/discarded specimen may be used. Specimens will be stored under appropriate refrigeration (-80) at the Irkutsk Oblast Tuberculosis Dispensary and at UVa, MR6 Building Room 1701A, IBC# 327-05. Further HPLC analysis of the plasma will be conducted by Charles Peloquin, Pharm.D., FCCP (University of Florida).

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Eric R Houpt, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eric R Houpt, MD

CONTACT

434-924-5167; erh6k@virginia.edu

Oleg B Ogarkov, MD

CONTACT

7-914-876-35-82

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Medicine, Infectious Diseases

Study Record Dates

• First Submitted: May 24, 2015
• First Posted: July 27, 2015
• Study Start: November 1, 2013
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: May 12, 2016

Record last verified: 2016-05

Locations

RU (1)