Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Salivary Therapeutic Drug Monitoring of Anti-Tuberculosis Drugs

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: NCT03080012
Recruitment Status : Completed
First Posted : March 15, 2017
Last Update Posted : November 21, 2018
Sponsor:
Information provided by (Responsible Party):
Jan-Willem C Alffenaar, University Medical Center Groningen

Study Description
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
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.

Condition or disease Intervention/treatment
Tuberculosis Other: Saliva sampling Other: Plasma/serum sampling

Detailed Description:

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.

Study Design
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Observational
Actual Enrollment : 24 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: An Observational Study of Salivary Versus Blood Concentrations of Various Anti-Tuberculosis Drugs in Tuberculosis Patients
Actual Study Start Date : March 7, 2017
Actual Primary Completion Date : May 2, 2018
Actual Study Completion Date : May 2, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Groups and Cohorts
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Intervention Details:
  • Other: Saliva sampling
    Stimulated saliva samples are taken using cotton rolls.
  • Other: Plasma/serum sampling
    Simultaneously with saliva sampling.

Outcome Measures
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Saliva-plasma ratio or saliva-serum ratio [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Ratio of salivary versus blood concentration calculated with salivary and plasma/serum values of area under the time-concentration curve (AUC)


Secondary Outcome Measures :
  1. Salivary drug concentration [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Measured drug concentration in saliva

  2. Plasma/serum drug concentration [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Measured drug concentration in plasma or serum

  3. Area under the time-concentration curve (AUC) in saliva and plasma/serum [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Calculated in both saliva and plasma/serum using the drug concentration at all time points.

  4. Peak concentration (Cmax) in saliva and plasma/serum [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Calculated in both saliva and plasma/serum using the drug concentration at all time points.

  5. Time of peak concentration (Tmax) in saliva and plasma/serum [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Calculated in both saliva and plasma/serum using the drug concentration at all time points.

  6. Trough concentration (Cmin) in saliva and plasma/serum [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Calculated in both saliva and plasma/serum using the drug concentration at all time points.

  7. Clearance (Cl) in saliva and plasma/serum [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Calculated in both saliva and plasma/serum using the drug concentration at all time points.

  8. Half-life (t1/2) in saliva and plasma/serum [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Calculated in both saliva and plasma/serum using the drug concentration at all time points.

  9. Elimination constant (Kel) in saliva and plasma/serum [ Time Frame: 0, 0.5, 1, 2, 3, 4, 7 hours post-dose for isoniazid, rifampicin, ethambutol and pyrazinamide or 0, 1, 2, 3, 4, 8 hours post-dose for all other drugs ]
    Calculated in both saliva and plasma/serum using the drug concentration at all time points.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Tuberculosis patients of University Medical Center Groningen Beatrixoord, Haren, The Netherlands.
Criteria

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT03080012


Locations
Layout table for location information
Netherlands
University Medical Center Groningen (UMCG) Beatrixoord
Haren, Groningen, Netherlands, 9751ND
Sponsors and Collaborators
University Medical Center Groningen
Investigators
Layout table for investigator information
Principal Investigator: Jan-Willem Alffenaar, PhD, PharmD University Medical Center Groningen
More Information
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Jan-Willem C Alffenaar, PhD, PharmD, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT03080012    
Other Study ID Numbers: SALIV-01
First Posted: March 15, 2017    Key Record Dates
Last Update Posted: November 21, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Encoded data can be shared for scientific use up to 15 years after study completion.
Additional relevant MeSH terms:
Layout table for MeSH terms
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections