Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Tirapazamine

Cervical tissue biopsy analysis: Comet assay

Biopsy: Measurement of histone gamma H2AX phosphorylation

Biopsy: Immunohistochemistry: Ca9, Glut1, HIF-1 alpha

Measurement of vascular perfusion: contrast enhanced MRI

Christina Aquino-Parsons, MD

The purpose of this study is as follows:

* to determine whether tirapazamine damages cervical tumour DNA immediately after its administration
* to determine the blood flow and oxygen level of cervical tumour before and after treatment with tirapazamine

Patients with locally advanced cervical cancer can have a poor clinical outcome with standard cisplatin and pelvic radiation therapy. It is well established that pre-treatment tumor hypoxia is a significant prognostic factor in tumors and may be one of the most important and modifiable mechanisms of radiation resistance in this group of tumours. Significant levels of hypoxia are not present in all locally advanced cervical tumors. Hence measurement of the pretreatment tumour oxygenation status is imperative, and can be assessed using various means. Immunohistochemical staining of various intrinsic hypoxia markers to include Ca9, Glut1, HIF-1 alpha on the pre-treatment tumours can be performed.

Tirapazamine, a bio-reductively activated hypoxic cell selective anti-tumour agent, has been found to act synergistically with cisplatinum, resulting in a significantly higher cell kill than expected based on additive action. We proposed to measure the cell killing effect of tirapazamine with the following tests:

* Comet assay: Tirapazamine causes DNA damage that can predict for cell killing by measuring DNA damage in cells from tumor biopsies using the alkaline comet assay.
* Measurement of phosphorylation of histone gamma H2AX: It has been explored as a measure of radiosensitivity in response to clinically relevant doses of radiation. The histone gamma H2AX phosphorylation can be used to detect tirapazamine induced DNA double-strand breaks and collapsed replication forks.

There is some evidence that the drug delivery may be impaired and in fact the drug may not actually be reaching all of the hypoxic tumour cells. A recent study has shown that, in an experimental setting, tirapazamine causes a decrease in vascular perfusion which can be measured with contrast enhanced MRI. We propose to assess if this mechanism is operative in human tumours.

Clinical studies have demonstrated that tumour vascular can increase during the course of radiation therapy, consistent with re-oxygenation and that this is suggestive of a better outcome. Tumours that become less hypoxic during the course of therapy have an increased likelihood of response to the given treatment. However, response to tirapazamine may be reduced. In order to assess both the vascular change that may occur directly because of tirapazamine infusion, as well as any increase in tumour vascularity and perhaps increase in tumour oxygenation during the course of therapy, we plan to assess these tumours during the course of therapy. Assessment of tumour perfusion and vessel permeability after 10 radiation treatments (on day 12) of chemo-radiation therapy will be performed via T1 weighted dynamic contrast enhanced MRI (DCMRI).

We hypothesize that:

1. Tirapazamine (a hypoxic cell cytotoxin and radiosensitizer) will result in increased DNA damage and a better clinical outcome if:

   1. the pre-treatment tumor demonstrates significant hypoxia
   2. tirapazamine treatment results in increased DNA damage
2. tirapazamine acts, in part, by changing vascular perfusion in the tumour and that these changes can be measured with dynamic contrast enhanced MRI.

Study of Tumour Response to Tirapazamine During Treatment of Cervical Cancer

Prospective Study of Tirapazamine Targeting in Cervical Cancer

Canadian Institutes of Health Research (CIHR)

British Columbia Cancer Agency

Nutritional and Metabolic Diseases

Gland and Hormone Related Diseases

Diabetes Mellitus

Diabetes Mellitus, Type 2

Metabolic Diseases

Glucose Metabolism Disorders

Endocrine System Diseases

Karl-Heinz Wagner, PhD

Annemarie Grindel

Helmuth Brath, MD

The purpose of the study is to determine whether glycemic control (HbA1c) is linked to chromosomal damage in type 2 Diabetes patients

Chromosomal Damage in Type 2 Diabetes Patients (MIKRODIAB)

Incidence of Chromosomal Damage in Type 2 Diabetes Patients

In this cross-sectional study the micronuclei formation in binucleated lymphocytes (Number of micronuclei/1000 binucleated cells) is compared between a low (HbA1c\<7.5%) and a high (HbA1c\>7.5%) glycemic group

The micronuclei formation in binucleated lymphocytes (Number of micronuclei/1000 binucleated cells) is associated with the duration of the Typ 2 diabetes disease.

University of Vienna

Director Research Platform Active Ageing

Heart and Blood Diseases

Wounds and Injuries

Hyperemia

Heat Stress Disorders

Vascular Diseases

Hormones

Follicle Stimulating Hormone

Complement System Proteins

Imidacloprid

Baseline measurements will be performed in the same schedule as measurements in the three other arms. In the baseline session, participants are in classroom before starting any firefighting exercise

Firefighting equivalent work, with exercises performed in a clean environment, without fire (no ambient temperature, soot or smoke). This type of exercise usually precedes or complements the training under real fire conditions.

Firefighting under wood fire, with exposure to ambient heat, smoke and soot. This is the most common training scenario used in the training centres. The participants will be in teams performing pre-defined tasks (knocking down the fire, moving heavy objects, and searching and rescuing metal stand in models

Firefighting under gas fire, with exposure to ambient heat, and expectably less smoke and soot than with wood fire. These conditions are used in some Danish training centres, with logistical advantages (ease of turning or putting out the fire and managing the fire fuel) and unknown effect relating to exposure prevention (smoke and soot). The participants will be in teams performing pre-defined tasks (knocking down the fire, moving heavy objects, and searching and rescuing metal stand in models

The participants will be performing firefighting equivalent work in a clean environment, without fire (no ambient temperature, soot or smoke).

Firefighting training exercises with no fire

The participants will be in teams performing pre-defined tasks (knocking down the fire, moving heavy objects, and searching and rescuing metal stand in models), under wood fire conditions.

Firefighting training exercises under wood fire

The participants will be in teams performing pre-defined tasks (knocking down the fire, moving heavy objects, and searching and rescuing metal stand in models), under gas fire conditions.

Firefighting training exercises under gas fire

Maria Helena G Andersen, PhD

Anne T Saber, PhD

Maria Helena Guerra Andersen

Epidemiological studies based on Danish registries have observed that Danish male firefighters have more cardiovascular disease, infertility diagnose and a trend to increased risk of cancer than other Danish employed males. Firefighting activities include a combination of stressors such as strenuous work under heat, smoke and soot known to be able to affect cardiovascular and reproductive health, with smoke and soot also being known to increase the risk of cancer.

The training facilities of real-fire extinguishing exercises in Denmark operate using wood or natural gas fire, which will have differential gradients of smoke, soot and possibly heat. The investigators will use different training conditions to create gradients of the different stressors and investigate health effects thereof. With this approach, the investigators expect to be able to evaluate the individual contribution of the different stressors in markers of cardiovascular, cancer and reproductive health risk. The project will include approx. 35 young conscript participants on a firefighting course, followed in four sessions, three firefighting training sessions under different fire conditions (no fire, wood fire and gas fire) and one control scenario.

The study methodology is based on a crossover design on firefighting training under different conditions, with characterization of exposure and assessment of cardiovascular, cancer and reproductive effect biomarkers. The study will be performed in cooperation with the Danish Emergency Management Agency.

The study will have one baseline session, while conscripts are in a classroom, and three sessions of firefighting-related exercises under different fire conditions, used currently in firefighting training programs in Denmark. The three firefighting training sessions will be controlled for equivalent work exercise using full protective gear and under different ambient conditions of firefighting training:

* Firefighting equivalent work (no fire), with exercises performed in a clean environment, without fire (no ambient temperature, soot or smoke). This type of exercise precedes or complements the training under real fire conditions.
* Firefighting under wood fire (wood fire), with exposure to ambient heat, smoke and soot. This is the most common training scenario used by Danish Emergency Management Agency training centres.
* Firefighting under gas fire (gas fire), with exposure to ambient heat, and expectably less smoke and soot than with wood fire. These conditions are used in some Danish training centres, with logistical advantages (ease of turning or putting out the fire and managing the fire fuel) and unknown effect relating to exposure prevention (smoke and soot).

The order of the firefighting sessions will be as randomized as possible, and according to a selection of three sequence order options (no-wood-gas; wood-gas-no and gas-wood-no). Each campaign (corresponding to each rescue course) would desirably have one of these session sequences. It is not possible to blind the participants to the different scenarios, neither the field staff, but all the samples will be blinded for the subsequent laboratory analysis. The training sessions will have 1-3 weeks in between (accordingly with programmatic educational course schemes).

Participants will perform firefighting full day exercises under 3 different conditions (without fire, under wood fire and under gas fire), sessions which will occur with weeks in between, and biological markers will be assessed and compared in relation to a baseline session, where the participants are having theoretical classes.

It is not possible to blind the participants to the different scenarios, neither the field staff, but all the samples will be blinded for the subsequent laboratory analysis, namely blood analysis, urine analysis, wipe samples analysis will all be blinded.

Effect on Markers of Cardiovascular, Reproductive and Cancer Risk From Firefighting Training

Effect on Markers of Cardiovascular, Reproductive and Cancer Risk From Firefighting Activities - a Study Under Different Training Methods

Supportive information and fully anonymized information will be shared and whenever possible (in supplementary material) published along with the results, but following European Union General Data Protection Regulation (GDPR) and Danish rules, no non or pseudo anonymized data might be shared.

Reactive hyperemia index (RHI) measured with the device EndoPAT 2000. A reactive hyperemia is induced by a blood cuff on the upper arm and the peripheral vasodilation response is assessed in the small digital vessels of a fingertip with a portable device connected to a computer, with RHI determined by an algorithm from the device, with lower index values corresponding to a worsen situation.

Heart rate variability (HRV) measured with the device EndoPAT 2000. The HRV is calculated using the initial 5.5 complete minutes before the cuff is applied. pNN50 is the proportion of successive NN intervals differing by more than 50 milliseconds divided by the total number of N intervals (given in percentage).

Heart rate variability (HRV) measured with the device EndoPAT 2000. The HRV is calculated using the initial 5.5 complete minutes before the cuff is applied. RMSSD is the square root of the mean squared differences of successive NN intervals (given in milliseconds)

Heart rate variability (HRV) measured with the device EndoPAT 2000. The HRV is calculated using the initial 5.5 complete minutes before the cuff is applied. Ratio of low frequency and high frequency bands

Oxidized nucleobase 8-oxodG will be measured in urine samples by High-performance liquid chromatography (HPLC) as marker of oxidative stress, together with creatinine, for adjusting for urine concentration. Data will be reported as nanomol 8-oxodG per millimol creatinine.

DNA strand breaks will be measured by comet assay, and reported as number of lesions per 10\^6 base pairs, transformed from percentage of DNA in tail using the calibration curve from the well-establish relationship between ionizing radiation dose and yield of strand breaks in DNA.

Core body temperature will be assessed by an ingestible pill thermometer with data recorded and reported as time series during the period in transit.

Scrotal temperature will be assessed by skin sensor placed in the scrotum of male participants and reported as scrotal skin temperature time series.

Core body temperature will be assessed by an ingestible pill thermometer and scrotal temperature will be assessed by skin sensor placed in the scrotum of male participants, to assess the thermoregulation of the scrotum during firefighting exercises. Time series of core body temperature and scrotal skin temperature will be analysed for eventual thermoregulation disruption.

Circulating micro RNA candidates will be measured by RNA extraction from serum samples, reverse transcribed into complementary DNA (cDNA) and analysed with quantitative polymerase chain reaction (qPCR).

The aryl hydrocarbon receptor (AhR) activation will be assessed in vitro using urine samples on the PAH CALUX (Chemical Activated LUciferase gene eXpression bioassay) reporter assay. The smoke and soot exposures are complex mixtures of compounds with potential toxic effect. Routine measurements of PAHs are usually quantified for a target list of 16 common soot elements and even less chemical species for urinary metabolites, but many other compounds are present in both soot and metabolites mixtures. The toxicity of PAHs is primarily caused through the binding to AhR, and induction of AhR related genes and subsequent toxic pathways. The outcome will be measured in the form of benzo\[a\]pyrene equivalence.

The aryl hydrocarbon receptor (AhR) activation will be assessed in vitro using wipe samples on the PAH CALUX (Chemical Activated LUciferase gene eXpression bioassay) reporter assay. The smoke and soot exposures are complex mixtures of compounds with potential toxic effect. Routine measurements of PAHs are usually quantified for a target list of 16 common soot elements, but many other compounds are present in soot mixtures. The toxicity of PAHs is primarily caused through the binding to AhR, and induction of AhR related genes and subsequent toxic pathways. The outcome will be measured in the form of benzo\[a\]pyrene equivalence.

Follicle-stimulating hormone (FSH) will be measured in serum samples

Inhibin B hormone will be measured in serum samples

The internal dose of polycyclic aromatic hydrocarbons (PAHs), that would have the contribution from different exposure routes, will be assessed in first morning urine samples and measured for 7 isomer hydroxyl-PAH compounds and 5 nitro-PAH compounds, measured by high-performance liquid chromatography (HPLC)

Skin wipes will be sampled to determine the PAH composition of deposited soot on the neck area. The wipes will be analysed for the 16 US Environmental Protection Agency priority list of PAH compounds by HPLC.

Lung function will be measured by spirometry using the Spirometer device EasyOne Air. Forced Expiratory Volume at 1 second (FEV1).

Lung function will be measured by spirometry using the Spirometer device EasyOne Air. Forced Vital capacity (FVC).

Lung function will be measured by spirometry using the Spirometer device EasyOne Air. Peak Expiratory Flow (PEF).

Lung function will be measured by spirometry using the Spirometer device EasyOne Air. Forced Expiratory Volume at 1 second (FEV1) and Forced Vital Capacity (FVC) ratio is calculated from device output.

Cardiac troponin levels using ELISA immunoassays will be assessed in serum samples.

Muscle activity will be assessed to control for body workload through electromyography (EMG) using the portable device Nexus10. Bipolar surface EMG electrodes are applied to the skin over the muscles in 3 relevant body regions (shoulder, leg and back). The signals are collected with a data logger and reported as work load during a working day.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Tumour Response to Tirapazamine During Treatment of Cervical Cancer	NCT00493376	Cervix Cancer	Cervical tissue... Biopsy: Measure... Biopsy: Immunoh... Measurement of ...	18 Years -	British Columbia Cancer Agency
Chromosomal Damage in Type 2 Diabetes Patients (MIKRODIAB)	NCT02231736	Type 2 Diabetes Cancer		30 Years -	University of Vienna
Effect on Markers of Cardiovascular, Reproductive and Cancer Risk From Firefighting Training	NCT05753254	Reactive Hypere... Micro RNA Heart Rate Vari... DNA Strand Brea... Oxidative Stres... Heat Stress	Firefighting tr... Firefighting tr... Firefighting tr...	18 Years -	National Research Centre for the Working Environment, Denmark
Chromosomal Damage in Type 2 Diabetes Patients (MIKRODIAB)	NCT02231736	Type 2 Diabetes Cancer		30 Years -	University of Vienna
Effect on Markers of Cardiovascular, Reproductive and Cancer Risk From Firefighting Training	NCT05753254	Reactive Hypere... Micro RNA Heart Rate Vari... DNA Strand Brea... Oxidative Stres... Heat Stress	Firefighting tr... Firefighting tr... Firefighting tr...	18 Years -	National Research Centre for the Working Environment, Denmark

Spots Global Cancer Trial Database for comet assay

Every month we try and update this database with for comet assay cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for comet assay

Every month we try and update this database with for comet assay cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for comet assay cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.