Salivary Therapeutic Drug Monitoring of Anti-Tuberculosis Drugs

NCT ID: NCT03080012

Last Updated: 2018-11-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

24 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-03-07

Study Completion Date

2018-05-02

Brief Summary

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In tuberculosis patients, salivary concentrations will be compared to plasma/serum concentrations of several anti-tuberculosis drugs. If salivary concentrations correctly represent blood concentrations, this non-invasive sampling of saliva could be used for TDM of the tested drugs.

Detailed Description

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TDM (Therapeutic Drug Monitoring) with blood samples is already part of the treatment of some tuberculosis (TB) patients to reduce development of drug resistance and toxic drug concentrations. Performing TDM with saliva instead of plasma or serum could reduce the burden of blood sampling. This study examines if this non-invasive sampling of saliva could be used for TDM of several anti-TB drugs.

The study is an observational cohort study with adult tuberculosis patients as subjects. The drugs that are studied are isoniazid, rifampicin, ethambutol, pyrazinamide, moxifloxacin, amikacin, kanamycin, capreomycin, ethionamide, prothionamide, cycloserine, terizidone, linezolid, clofazimine, bedaquiline, delamanid, p-aminosalicylic acid (PAS), imipenem-cilastatin, meropenem, ertapenem, amoxicillin-clavulanate and thioacetazone.

Saliva samples will be taken simultaneously with blood samples for standard TDM. Serum/plasma and saliva drug concentrations will be determined with a validated LC-MS/MS (liquid chromatography-tandem mass spectrometry) method. The correlation and linearity between saliva and plasma/serum concentrations will be tested. The saliva-plasma or serum ratio based on area under the time-concentration curve (AUC) is calculated for the investigated anti-TB drugs. Also pharmacokinetic parameters in serum/plasma and saliva will be calculated and compared to provide a complete image of pharmacokinetics of the anti-TB drugs in saliva.

Conditions

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Tuberculosis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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Saliva sampling

Stimulated saliva samples are taken using cotton rolls.

Intervention Type OTHER

Plasma/serum sampling

Simultaneously with saliva sampling.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Tuberculosis is confirmed by culture or molecular test
* Patient is treated with anti-tuberculosis drugs included in study
* Patient receives Therapeutic Drug Monitoring (TDM) in routine care
* Patient signed informed consent

Exclusion Criteria

* Patient with severe problems in the oral cavity, making saliva sampling painful
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Medical Center Groningen

OTHER

Sponsor Role lead

Responsible Party

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Jan-Willem C Alffenaar

PhD, PharmD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jan-Willem Alffenaar, PhD, PharmD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

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University Medical Center Groningen (UMCG) Beatrixoord

Haren, Provincie Groningen, Netherlands

Site Status

Countries

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Netherlands

References

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van den Elsen SHJ, Akkerman OW, Wessels M, Jongedijk EM, Ghimire S, van der Werf TS, Bolhuis MS, Touw DJ, Alffenaar JC. Dose optimisation of first-line tuberculosis drugs using therapeutic drug monitoring in saliva: feasible for rifampicin, not for isoniazid. Eur Respir J. 2020 Oct 22;56(4):2000803. doi: 10.1183/13993003.00803-2020. Print 2020 Oct. No abstract available.

Reference Type DERIVED
PMID: 32398308 (View on PubMed)

van den Elsen SHJ, Akkerman OW, Jongedijk EM, Wessels M, Ghimire S, van der Werf TS, Touw DJ, Bolhuis MS, Alffenaar JC. Therapeutic drug monitoring using saliva as matrix: an opportunity for linezolid, but challenge for moxifloxacin. Eur Respir J. 2020 May 7;55(5):1901903. doi: 10.1183/13993003.01903-2019. Print 2020 May. No abstract available.

Reference Type DERIVED
PMID: 31980497 (View on PubMed)

van den Elsen SHJ, Akkerman OW, Huisman JR, Touw DJ, van der Werf TS, Bolhuis MS, Alffenaar JC. Lack of penetration of amikacin into saliva of tuberculosis patients. Eur Respir J. 2018 Jan 11;51(1):1702024. doi: 10.1183/13993003.02024-2017. Print 2018 Jan. No abstract available.

Reference Type DERIVED
PMID: 29326320 (View on PubMed)

Other Identifiers

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SALIV-01

Identifier Type: -

Identifier Source: org_study_id

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