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Early Diagnosis of Kidney Damage Associated With Tobacco Use

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ClinicalTrials.gov Identifier: NCT03850756
Recruitment Status : Recruiting
First Posted : February 22, 2019
Last Update Posted : May 6, 2020
Sponsor:
Collaborators:
Instituto de Investigación Biomédica de Salamanca
Grupo de Investigación de Atención Primaria de Castilla y León
Salamanca University Hospital
Instituto de Salud Carlos III
Information provided by (Responsible Party):
Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León

Brief Summary:

Tobacco consumption is associated with the appearance of several pathologies, the best known are Chronic Obstructive Pulmonary Disease, several types of cancer and cardiovascular diseases. However, the association between tobacco and kidney damage is not well defined. Some studies suggest that smoking favors progression to chronic kidney disease (CKD). CKD does not have pharmacological treatment and the only clinical strategies useful so far are dialysis or kidney transplantation. Therefore, knowing if tobacco is involved in this disease is a very relevant fact, since it is a modifiable factor. Of all the risk factors associated with the onset and progression of kidney disease is the only one that can be avoid or eliminated. Therefore quitting smoking could help reduce the incidence of this pathology.

In this project, 3 main objectives were proposed:

  1. First: to study the tobacco-CKD association in a more exhaustive way. In a population group (patients who attend a primary care center) the renal function of smokers will be evaluated, comparing it with that of non-smokers with similar characteristics (age, sex, etc). In addition, the presence of certain pathologies that can affect the kidney (diabetes mellitus, hypertension and / or frequent consumption of certain medications) will be taken into account. To evaluate the renal functionality, the markers commonly used in the clinic and other more novel ones will be used (urinary biomarkers of early kidney damage).
  2. Second: to assess whether smoking patients will be more likely to suffer kidney damage in the future. This will be done by monitoring the patients mentioned above, for two years. During this time, a group of novel markers (urinary biomarkers of predisposition to kidney damage) that in previous studies have detected susceptibility to kidney damage will be evaluated. It will be determined which one or more of these markers are capable of predicting at time 0 (when the first sample of the patient is taken) the subsequent appearance of renal damage.
  3. Third: to study whether stopping smoking reduces the risk of developing CKD. It will be evaluated whether stopping smoking reduces the susceptibility to kidney damage by using the biomarkers mentioned above.

Condition or disease Intervention/treatment
Kidney Injury Kidney Disease, Chronic Tobacco Toxicity Diagnostic Test: Early kidney damage biomarkers Diagnostic Test: Predisposition to kidney injury biomarkers Diagnostic Test: Tobacco consumption

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Study Type : Observational
Estimated Enrollment : 600 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: New Diagnostic System for the Early Detection of Chronic Renal Damage Associated to Tobacco Consumption: Preventive and Personalized Application
Actual Study Start Date : March 4, 2019
Estimated Primary Completion Date : April 1, 2022
Estimated Study Completion Date : July 1, 2022

Group/Cohort Intervention/treatment
1: No smokers without risk factors

A smoker is defined as: any person who habitually consumes tobacco at the time of taking the sample or who has left it in the last 12 months (WHO, 2008).

The following circumstances involved in the development of kidney damage will be considered a risk factor: Diabetes Mellitus, Hypertension and / or frequent use of NSAIDs (more than three days a week during the three months prior to sampling)

In these patients kidney function will be evaluated by:

Early kidney damage biomarkers Predisposition to kidney injury biomarkers

Diagnostic Test: Early kidney damage biomarkers
In the urine samples of these patients, a series of biomarkers of early kidney damage and / or predisposition to kidney damage will be measured.
Other Names:
  • albumin
  • N-acetyl-beta-D-glucosaminidase (NAG)
  • Kidney Injury Molecule-1 (KIM-1)
  • Neutrophil gelatinase-associated lipocalin (NGAL)
  • T-gelsolin

Diagnostic Test: Predisposition to kidney injury biomarkers
In the urine samples of these patients, a series of biomarkers of predisposition to kidney damage will be measured.

2: No smokers with risk factors

A smoker is defined as: any person who habitually consumes tobacco at the time of taking the sample or who has left it in the last 12 months (WHO, 2008).

The following circumstances involved in the development of kidney damage will be considered a risk factor: Diabetes Mellitus, Hypertension and / or frequent use of NSAIDs (more than three days a week during the three months prior to sampling)

In these patients kidney function will be evaluated by:

Early kidney damage biomarkers

Diagnostic Test: Early kidney damage biomarkers
In the urine samples of these patients, a series of biomarkers of early kidney damage and / or predisposition to kidney damage will be measured.
Other Names:
  • albumin
  • N-acetyl-beta-D-glucosaminidase (NAG)
  • Kidney Injury Molecule-1 (KIM-1)
  • Neutrophil gelatinase-associated lipocalin (NGAL)
  • T-gelsolin

3: Smokers without risk factors

A smoker is defined as: any person who habitually consumes tobacco at the time of taking the sample or who has left it in the last 12 months (WHO, 2008).

The following circumstances involved in the development of kidney damage will be considered a risk factor: Diabetes Mellitus, Hypertension and / or frequent use of NSAIDs (more than three days a week during the three months prior to sampling)

In these patients kidney function will be evaluated by:

Early kidney damage biomarkers Predisposition to kidney injury biomarkers

Also tobacco consumption will be measured

Diagnostic Test: Early kidney damage biomarkers
In the urine samples of these patients, a series of biomarkers of early kidney damage and / or predisposition to kidney damage will be measured.
Other Names:
  • albumin
  • N-acetyl-beta-D-glucosaminidase (NAG)
  • Kidney Injury Molecule-1 (KIM-1)
  • Neutrophil gelatinase-associated lipocalin (NGAL)
  • T-gelsolin

Diagnostic Test: Predisposition to kidney injury biomarkers
In the urine samples of these patients, a series of biomarkers of predisposition to kidney damage will be measured.

Diagnostic Test: Tobacco consumption
In order to know the degree of tobacco consumption, the biomarker cotinine will be measured in the urine samples of these patients.

4: Smokers without risk factors

A smoker is defined as: any person who habitually consumes tobacco at the time of taking the sample or who has left it in the last 12 months (WHO, 2008).

The following circumstances involved in the development of kidney damage will be considered a risk factor: Diabetes Mellitus, Hypertension and / or frequent use of NSAIDs (more than three days a week during the three months prior to sampling)

In these patients kidney function will be evaluated by:

Early kidney damage biomarkers

Also Tobacco consumption will be measured

Diagnostic Test: Early kidney damage biomarkers
In the urine samples of these patients, a series of biomarkers of early kidney damage and / or predisposition to kidney damage will be measured.
Other Names:
  • albumin
  • N-acetyl-beta-D-glucosaminidase (NAG)
  • Kidney Injury Molecule-1 (KIM-1)
  • Neutrophil gelatinase-associated lipocalin (NGAL)
  • T-gelsolin

Diagnostic Test: Tobacco consumption
In order to know the degree of tobacco consumption, the biomarker cotinine will be measured in the urine samples of these patients.




Primary Outcome Measures :
  1. Change of urinary albumin [ Time Frame: For objectives 1 and 2 (2 years): 0 and 24 months. For the objective 3 (1 year): 0, 3, 6 and 12 months ]
    It is a biomarker of early kidney damage. It is able to detect kidney damage in the early stages, before the clinical markers creatinine and plasma urea. There are no reference values for humans, so the means of non-smoking patients without risk factors (group 1) should be compared with the rest of the groups. This biomarker will be measured at different times to evaluate its evolution and compare it against the baseline value.

  2. Change of urinary N-Acetyl-β-D-Glucosaminidase (NAG) [ Time Frame: For objectives 1 and 2 (2 years): 0 and 24 months. For the objective 3 (1 year): 0, 3, 6 and 12 months ]
    It is an enzyme whose urinary excretion is elevated in case of kidney damage. It is capable of detecting damage before the classic plasma creatinin and urea markers. There are no reference values for humans, so the means of non-smoking patients without risk factors (group 1) should be compared with the rest of the groups. This biomarker will be measured at different times to evaluate its evolution and compare it against the baseline value.

  3. Change of urinary Kidney Injury Molecule-1 (KIM-1) [ Time Frame: For objectives 1 and 2 (2 years): 0 and 24 months. For the objective 3 (1 year): 0, 3, 6 and 12 months ]
    It is a biomarker of early kidney damage. It is able to detect kidney damage in the early stages, before the clinical markers creatinine and plasma urea. There are no reference values for humans, so the means of non-smoking patients without risk factors (group 1) should be compared with the rest of the groups. This biomarker will be measured at different times to evaluate its evolution and compare it against the baseline value.

  4. Change of urinary Neutrophil gelatinase-associated lipocalin (NGAL) [ Time Frame: For objectives 1 and 2 (2 years): 0 and 24 months. For the objective 3 (1 year): 0, 3, 6 and 12 months ]
    It is a biomarker of early kidney damage. It is able to detect kidney damage in the early stages, before the clinical markers creatinine and plasma urea. There are no reference values for humans, so the means of non-smoking patients without risk factors (group 1) should be compared with the rest of the groups. This biomarker will be measured at different times to evaluate its evolution and compare it against the baseline value.

  5. Change of urinary T-gelsolin. [ Time Frame: For objectives 1 and 2 (2 years): 0 and 24 months. For the objective 3 (1 year): 0, 3, 6 and 12 months ]
    It is a biomarker of early kidney damage. It is able to detect kidney damage in the early stages, before the clinical markers creatinine and plasma urea. There are no reference values for humans, so the means of non-smoking patients without risk factors (group 1) should be compared with the rest of the groups.This biomarker will be measured at different times to evaluate its evolution and compare it against the baseline value.

  6. Change of urinary biomarkers of predisposition to kidney injury [ Time Frame: For objectives 1 and 2 (2 years): 0 and 24 months. For the objective 3 (1 year): 0, 3, 6 and 12 months ]
    It is a group of markers that are in patent phase so their names can not be mentioned. They are able to detect the susceptibility to kidney damage before administering a nephrotoxic agent. There are no reference values for humans, so the means of non-smoking patients without risk factors (group 1) should be compared with the rest of the groups. This biomarker will be measured at different times to evaluate its evolution and compare it against the baseline value.


Secondary Outcome Measures :
  1. Percentage of patients with Risk factor's [ Time Frame: These data will be collected once, at time 0 (moment of inclusion in the study) ]
    The percentage of participants who suffer each of the following pathologies / conditions (risk factors), in each study group, will be consulted through the clinical history: diabetes mellitus, hypertension, frequent use of NSAIDs.

  2. Body weight [ Time Frame: These data will be collected once, at time 0 (moment of inclusion in the study) ]
    Body weight will be measured to each patient and expressed in kilograms

  3. Height [ Time Frame: These data will be collected once, at time 0 (moment of inclusion in the study) ]
    The height will be measured to each patient and expressed in meters

  4. Body mass index (BMI) [ Time Frame: These data will be collected once, at time 0 (moment of inclusion in the study) ]
    Weight and height will be combined to report BMI in kg/m^2

  5. Age [ Time Frame: These data will be collected once, at time 0 (moment of inclusion in the study) ]
    Through the year of birth, the patient's age will be calculated, which will be expressed in years.

  6. Sex [ Time Frame: These data will be collected once, at time 0 (moment of inclusion in the study) ]
    Patients will be classified according to sex in Male or Female

  7. Concentration of plasma creatinine [ Time Frame: These data will be collected once, at time 0 (moment of inclusion in the study) ]
    From the analytical biochemistry performed on the patient as part of his usual procedure, the plasma creatinine data will be obtained in mg/dL units.

  8. Concentration of plasma urea [ Time Frame: These data will be collected once, at time 0 (moment of inclusion in the study) ]
    From the analytical biochemistry performed on the patient as part of his usual procedure, the plasma urea data will be obtained in mg/dL units.

  9. Quantitative determination of tobacco consumption [ Time Frame: For objectives 1 and 2: 0 and 24 months. For the objective 3: 0, 3, 6 and 12 months. ]
    The urinary excretion of cotinine (tobacco metabolite) in urine will be measured for which a commercial diagnostic kit (ELISA) will be used and expressed as ng/mL. Additionally, if in the biochemical analysis the concentration of cotinine in blood has been determined, this data will be collected and expressed as ng/mL.

  10. Lung capacity [ Time Frame: These data will be collected once, at time 0 (moment of inclusion in the study) ]
    In objective 3, lung capacity will be evaluated with a co-oximeter, and it will be expressed in parts per million (ppm)


Biospecimen Retention:   Samples Without DNA
In this project, only urine samples will be collected. This will be centrifuged, aliquoted and stored at -80 degrees Celsius until its determination.


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 to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
This study will be carried out with the general population, specifically patients who attend a Primary Care consultation (Objectives 1 and 2), and people who come to the Smoking Unit to try to stop smoking (Objective 3)
Criteria

Inclusion Criteria:

  • Patients of legal age who agree to participate in the study and do not comply with any of the exclusion criteria

Exclusion Criteria:

  • Patients who are terminally ill; presenting previously diagnosed renal failure
  • Patients that during the week prior to the sample collection, or at the time of the sample, have been treated with any of the following drugs: aminoglycosides, cephalosporins, tetracyclines, amphotericin B, cisplatin, cyclosporine, foscarnet, acyclovir, cidofovir, radiological contrasts or any other potentially nephrotoxic drug.
  • Patients who do not wish to sign the informed consent

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): NCT03850756


Contacts
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Contact: Ana Isabel Morales Martín, PhD +34 923294400 ext 1862 amorales@usal.es
Contact: Laura Vicente Vicente, PhD +34 923294400 ext 1480 lauravicente@usal.es

Locations
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Spain
Centro de Salud La Alamedilla Recruiting
Salamanca, Spain
Contact: Luis García Ortíz, Doctor    +34 923231859    alamedilla.investigacion@gmail.com   
Unidad de tabaquismo del CAUSA Recruiting
Salamanca, Spain
Contact: Miguel Barrueco Ferrero, Doctor    +34 923291100 ext 55536      
Sponsors and Collaborators
Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
Instituto de Investigación Biomédica de Salamanca
Grupo de Investigación de Atención Primaria de Castilla y León
Salamanca University Hospital
Instituto de Salud Carlos III
Investigators
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Principal Investigator: Ana Isabel Morales Martín, PhD University of Salamanca
  Study Documents (Full-Text)

Documents provided by Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León:
Informed Consent Form  [PDF] December 19, 2017

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
ClinicalTrials.gov Identifier: NCT03850756    
Other Study ID Numbers: BIOTAB
First Posted: February 22, 2019    Key Record Dates
Last Update Posted: May 6, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León:
Biomarker
Tobacco
Nephrotoxicity
Prevention
Diagnosis
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency