Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Esophageal Neoplasms

Stomach Neoplasms

Barrett Esophagus

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Head and Neck Neoplasms

Esophageal Diseases

Precancerous Conditions

Esophageal Cancer

Stomach Cancer

Participants with gastroesophageal cancer providing a breath and blood sample for biomarker identification

Participants with Barrett's esophagus providing a breath and blood sample for biomarker identification

Healthy controls providing a breath and blood sample for biomarker identification

Detection of proteins and volatile organic compounds (oncometabolites) in the exhaled breath

Breath analysis

Detection of proteins and circulating tumor DNA (oncometabolites) in the peripheral blood

Blood analysis

Stijn Vanstraelen, MD

Philippe Nafteux, MD, PhD

The goal of this minimally invasive interventional study is to learn if oncometabolic biomarkers, detected in the exhaled breath and blood can identify early-stage gastro-oesophageal cancer in patient at risk for gastro-oesophageal cancer.

The main questions this study aims to answer:

Are oncometabolites proficient and reproducible enough to function as diagnostic biomarkers? Can these biomarkers identify early-stage gastro-esophageal cancer? Researchers will compare participants with gastro-oesophageal cancer to healthy controls and participants with Barrett's esophagus to detect meaningful differences between the groups.

Participants will provide a breath and blood sample during their routine standard of care visits.

Participants with gastro-esophageal cancer, participants with Barrett's esophagus and Healthy controls will be monitored in parallel to identify oncometabolic biomarkers related to cancer

Molecular Assessment for Gastro-Esophageal Cancer

Data will be shared upon reasonable request with the principal investigator.

Identify the concentrations of cancer-related metabolites (oncometabolites) in the exhaled breath and blood compared to healthy controls

Distinguish early-stage gastro-oesophageal cancer from Barrett's esophagus and healthy controls based on sensitivity, specificity and accuracy of the oncometabolite concentration

Predict and assess therapy response prior to surgery, based on sensitivity, specificity and accuracy of the oncometabolite concentration

Assess changes in the concentrations of the oncometabolites related to treatment.

Predict and assess recurrence, based on sensitivity, specificity and accuracy of the oncometabolite concentration

KU Leuven

Principal investigator

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

During patients' Endobronchial Ultrasound (EBUS) procedure, they will first undergo:

Selective Targeted Sampling - endosonographic assessment of at least 3 mediastinal lymph node stations (4R, 4L, and 7) using the four criteria of the Canada Lymph Node Score (predictor of nodal disease during Endobronchial Ultrasound). Each lymph node will be assigned a CLNS ranging from 0 to 4. Triple Normal lymph nodes will be defined as those that appear normal on CT (diameter \< 1 cm), AND normal on PET (SUV \< 2.5), AND normal on EBUS (CLNS \< 2). Lymph nodes that are found to be Triple Normal will be marked as "Not for Biopsy", whereas all other lymph nodes will be biopsied.

Upon completion of Systematic Targeted Sampling, all patients will crossover and receive the standard of care:

Systematic Sampling - all lymph nodes previously marked as "Not for Biopsy" will be biopsied.

At the conclusion of the EBUS procedure, all nodal stations would have been sampled as is mandated by current guidelines.

Mediastinal lymph nodes are assessed with the CLNS, and only those appearing malignant with the score are biopsied. Triple Normal lymph nodes (normal appearing on PET, CT and EBUS) are not biopsied.

Selective Targeted Sampling

All examined mediastinal lymph nodes are biopsied, regardless of whether they appear normal during PET, CT and EBUS.

Systematic Sampling

Waël C Hanna, MDCM, MBA, FRCSC

Before deciding on treatment for patients with lung cancer, a critical step in the investigation is finding out whether the lymph nodes in the chest contain cancer cells. This is accomplished with a biopsy of the lymph nodes through the airway wall, known as Endobronchial Ultrasound-guided Transbronchial Needle Aspiration. Guidelines require that every single lymph node in the chest be biopsied through a process called Systematic Sampling. However, emerging data suggests that the lymph nodes that appear benign on imaging and ultrasound do not need a biopsy. A proposed alternative to the inefficient Systematic Sampling is the simplified Selective Targeted Sampling of the lymph nodes, whereby only lymph nodes that look malignant are biopsied. This trial will evaluate the simplified Selective Targeted Sampling of lymph nodes and compare it to Systematic Sampling to see whether it is equally as effective in staging lung cancer.

Treatment decisions in Non-Small Lung Cancer (NSCLC) are reliant on a thorough staging process that includes imaging with Computed Tomography (CT), Positron Emission Tomography (PET) and Systematic Sampling (SS) of mediastinal lymph nodes (LNs) by Endobronchial Ultrasound Transbronchial Needle Aspiration (EBUS-TBNA). Collectively, the results of these staging procedures dictate whether patients will be treated with surgery, radiation and/or chemotherapy. Current guidelines for SS through EBUS-TBNA mandate the biopsy of at least 3 mediastinal LN stations (4R, 4L and 7) in the chest, even if they appear normal on CT and PET scan. Despite improvements in diagnostic techniques and safety, LN biopsies remain onerous for the patient and costly to our healthcare system. SS is also unreliable, yielding inconclusive pathology results in 42.14% of cases, especially for Triple Normal LNs, which are LNs that appear normal on PET, and CT, and EBUS. In fact, SS results in mostly negative or inconclusive biopsies for Triple Normal LNs, which may be due in part to their very low probability (\< 6%) of malignancy. As such, the researchers have proposed to replace the onerous and unreliable process of SS by a simpler Selective Targeted Sampling (STS) staging process. In STS, Triple Normal LNs will not be biopsied, due to the very high negative predictive value (NPV) of malignancy. STS follows the simple notion that only LNs that have the potential to be malignant should be biopsied, whereas LNs which are very likely benign (i.e. Triple Normal LNs) should not be biopsied.

A prospective pan-Canadian, multicentered, non-inferiority crossover study design

The Canada Lymph Node Score Project: A Crossover Trial

Improving Preoperative Lung Cancer Staging Through the Canada Lymph Node Project: A Pan-Canadian Multicentered Crossover Trial

A margin of 5% or less would be considered satisfactory for STS to be deemed non-inferior to SS.

Sensitivity, specificity, negative predictive value and positive predictive value

Percentage of lymph nodes with inconclusive pathology from biopsy

Proportion of lymph nodes with a pathological diagnosis for both sampling methods

For each sampling method (sum of dollar costs for EBUS procedure)

Health Sciences Centre, Winnipeg, Manitoba

Royal Alexandra Hospital

Toronto General Hospital

Centre hospitalier de l'Université de Montréal (CHUM)

McGill University Health Centre/Research Institute of the McGill University Health Centre

St. Joseph's Healthcare Hamilton

Lead Investigator

Gland and Hormone Related Diseases

Diseases and Abnormalities at or Before Birth

Nervous System Diseases

Thyroid Diseases

Congenital Abnormalities

Pituitary Diseases

Hypothyroidism

Pituitary Neoplasms

Endocrine System Diseases

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

All Drugs and Chemicals

Hormones

Thyrotropin-Releasing Hormone

Hormone Antagonists

Subjects receiving TRH (Thyrotropin Releasing Hormone)

TRH (Thyrotropin Releasing Hormone)

Joanna Klubo-Gwiezdzinska, M.D.

This study will determine the safety and activity of a new formulation of thyrotropin-releasing hormone (TRH), a drug used for diagnosing and evaluating patients with certain thyroid gland abnormalities. Normal thyroid gland function depends on proper chemical signaling between the thyroid gland, the hypothalamus (the part of the brain where TRH is made), and the pituitary (another part of the brain). The TRH test helps assess this interaction. Production of the only FDA-approved preparation of TRH was stopped in July 2002. As a result, to have a continuous source of TRH available for NIH clinical and research purposes, the NIH Clinical Center (CC) Pharmacy Department produced a pharmaceutical grade formulation of TRH for patient use. This study will test the CC formulation in healthy volunteers to show that its activity and side effects are similar to those of the previously available commercial test preparation. It will then be studied in CC patients for whom the diagnostic test is recommended.

Healthy volunteers between 18 and 65 years of age and all patients requiring TRH evaluation of hypothalamic-pituitary-thyroid gland interaction may be eligible for this study. Patients include those with pituitary reserve, inconsistent thyroid function test, inappropriate TSH secretion, or pre- and post-operative evaluation of pituitary tumors. Normal volunteers will be screened with a medical history, physical examination, and blood tests. Women of child-bearing potential will be given a pregnancy test; pregnant and breast-feeding women may not participate.

The TRH test procedure will be the same for healthy volunteers and patients. All participants fast from midnight before the morning of the test. In the morning, a catheter (flexible plastic tube) is inserted into an arm vein for easy injection of the TRH and collection of blood samples. Blood pressure is monitored before and during the test. A blood sample is drawn, and then TRH is given through the catheter over a 1-minute period. Another nine blood samples are collected over a 3-hour period from the time of the TRH injection for measuring levels of various hormones. A total of less than 4 tablespoons of blood is taken for the test.

Thyrotropin releasing hormone (TRH) is a neuropeptide used in the diagnostic evaluation of patients with dysfunction of the hypothalamic-pituitary-thyroid (HPT) axis. In healthy individuals, administration of TRH intravenously results in pituitary secretion of thyrotropin \[thyroid-stimulating hormone (TSH)\], which in turn stimulates the thyroid gland release of thyroid hormones; thyroxine (T4) and triiodothyronine (T3). TRH stimulates the secretion of other pituitary hormones under normal physiologic as well as pathologic conditions.

Under this protocol, TRH is used for routine diagnostic testing and research studies in adults and children. It is produced by the Pharmaceutical Development Section of the Clinical Center Pharmacy at the NIH. The safety, activity and comparability of this preparation were demonstrated in a small group of normal volunteers prior to its release for diagnostic and research use.

Study of Thyrotropin-Releasing Hormone in Normal Volunteers and in Patients With Thyroid or Pituitary Abnormalities

Study of Thyrotropin Releasing Hormone in Patients With Thyroid or Pituitary Abnormalities

Serum TSH Levels in Response to TRH Administration

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Thyrotropin Releasing Hormone

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

This study was conducted under an IND because the TRH was produced at NIH after the FDA approved manufacturer stopped producing the product. The intent of the study was to provide TRH for diagnostic purposes for patients at the NIH.

Dr Joanna Klubo-Gwiezdzinska

2 participants did not have results drawn at 180 minutes

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Molecular Assessment for Gastro-Esophageal Cancer	NCT06346054	Esophageal Canc... Gastric Cancer Barrett Esophag...	Breath analysis Blood analysis	18 Years - 100 Years	KU Leuven
The Canada Lymph Node Score Project: A Crossover Trial	NCT04342377	Lung Cancer Non Small Cell ... Non-small Cell ... Non-small Cell ...	Selective Targe... Systematic Samp...	18 Years -	St. Joseph's Healthcare Hamilton
Study of Thyrotropin-Releasing Hormone in Normal Volunteers and in Patients With Thyroid or Pituitary Abnormalities	NCT00054756	Healthy Pituitary Disea... Thyroid Disease	TRH (Thyrotropi...	2 Years -	National Institutes of Health Clinical Center (CC)

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