Novel Molecular Spectrometric Biomarkers in Blood Plasma as an Early Diagnostic Tool in HCC

NCT04221347 | Unknown

• 1 other identifier: Does not exist, not required
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

Due to providing valuable clinical information while being minimally invasive, blood-based testing will most likely be a prerequisite for future large-scale screening of high-risk populations. As a variety of pathological processes, including carcinogenesis, may cause changes in both the concentration and the structure and spatial arrangement of body biomolecules, the spectroscopic analysis of blood-based derivatives appears to be an appropriate tool for the early detection thereof. The differences observed in the spectral response of healthy individuals and patients may also be specific to a particular type/stage of the disease and, thus, may serve as a reliable diagnostic marker. In order to find sufficiently specific and sensitive biomarkers of early stages of degenerative and cancerous diseases, the co-applicant group at the Department of Analytical Chemistry, University of Chemistry and Technology Prague (UCT Prague), developed a unique approach for the spectroscopic analysis of blood plasma. Using the highly specialized, structure-sensitive methods of chiroptical spectroscopy (electronic circular dichroism - ECD, Raman optical activity - ROA) combined with conventional infrared (IR) and Raman spectroscopy, the first pilot studies yielded promising results with respect to the identification of spectral markers for pancreatic cancer, colon cancer and type 1 diabetes mellitus. In addition, metabolomics appears to be a very progressive approach to finding potentially suitable molecules to distinguish between healthy and cancer-affected individuals. Therefore, the investigators believes that this multimodal approach will allow for the identification of hepatocellular carcinoma (HCC). In our research, the focus will be on the identification of novel biomarkers in blood plasma that would exhibit sufficient sensitivity and specificity to detect early and potentially curable HCC stages, and that would be potentially useful for routine screening of this disease in well-defined at-risk groups.

Conditions

Liver Cancer; Hepatocellular Carcinoma; Cirrhosis, Liver

Outcome Measures

Primary Outcomes (1)

• Detection of spectroscopic markers differences among specified groups

  The main aim is to identify potential HCC biomarkers accessible in blood by using methods of conventional molecular spectroscopy (Raman and infrared absorption) in combination with structure-sensitive chiroptical techniques (electronic circular dichroism and Raman optical activity) and a metabolomics analysis.

  6 yrs

Secondary Outcomes (2)

• Measure of sensitivity and specificity of identified biomarkers for diagnosis HCC

  6 yrs

• Measure of sensitivity and specificity of identified biomarkers for surveillance of HCC

  6 yrs

Study Arms (3)

Group A - Hepatocellular carcinoma

Patients with with proved hepatocellular carcinoma in cirrhosis. N=100

Other: blood sampling

Group B - Cirrhosis

Cirrhotics of multiple aethiology will be sampled for spectroscopy in order to detect possible differences among cirrhotics with and without subsequent hepatocellular carcinoma. N=100

Other: blood sampling

Group C - Healthy controls

Healthy controls - healthy military personnel. N=50

Other: blood sampling

Interventions

blood sampling OTHER

blood samples will be taken in specified time points

Group A - Hepatocellular carcinoma; Group B - Cirrhosis; Group C - Healthy controls

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Group A: cca 100 patients with liver cirrhosis with the HCC diagnosis confirmed according to standard diagnostic criteria published recently by EASL. Patients of all HCC stages according to BCLC (in our department cca 40-50 patients per year) will be included Group B: cca 100 patients with liver cirrhosis without HCC or dysplastic nodules at the time of examination and within the next 12 months of follow-up. The patients will be monitored by regular clinical visits with general laboratory exams and liver ultrasound in 6-month intervals (recommended surveillance for patients with liver cirrhosis in risk of HCC development) Group C: cca 50 healthy volunteers without liver cirrhosis (Czech Army active military personnel)

You may qualify if:

• Group A
• age 18-80 years, signed informed consent
• proved liver cirrhosis based on at least one of the following criteria: histopathological finding in liver biopsy, non-invasive procedures (transient elastography (Fibroscan by Echosens, France) and / or shear-wave elastography, evidence of portal hypertension, history of cirrhosis decompensation (variceal bleeding, jaundice, hepatic encephalopathy, ascites, edema)
• HCC confirmed by EASL diagnostic algorithm
• Group B
• age 18-80 years, signed informed consent proved liver cirrhosis based on at least one of the following criteria: histopathological finding in liver biopsy, noninvasive procedures (transient elastography (Fibroscan by Echosens, France) and or shear-wave elastography), evidence of portal hypertension, history of cirrhosis decompensation (variceal bleeding, jaundice, hepatic encephalopathy, ascites, edema)
• HCC excluded according to: EASL diagnostic algorithm at baseline, negative liver ultrasound (no suspicious nodule in cirrhosis) during at least 2 examinations in 6 - month intervals (e.g. 12 months after baseline)
• Group C
• age 18-65 years, signed informed consent
• approved Czech Army recruits and active military personnel after regular examinations with normal outcome (vital functions, ECG, blood count, blood biochemistry and urine tests, chest X-ray, physical examination)

You may not qualify if:

• severe co-morbidities (i.e. advanced chronic heart failure, chronic renal insufficiency stage 4 and above, long-term poorly compensated diabetes mellitus with severe complications)
• absence of liver cirrhosis
• history of any other cancer than HCC
• pregnancy
• estimated patient non-compliance and/or not signing of the informed consent

Sponsors & Collaborators

• Military University Hospital, Prague: lead
• University of Chemistry and Technology, Prague: collaborator

Study Sites (1)

Central Military Hospital

Prague, 16902, Czechia

RECRUITING

Related Publications (1)

• Hribek P, Vrtelka O, Kralova K, Klasova J, Fouskova M, Habartova L, Kubickova K, Kupsa T, Tuma T, Setnicka V, Urbanek P. Efficacy of blood plasma spectroscopy for early liver cancer diagnostics in obese patients. Ann Hepatol. 2024 Sep-Oct;29(5):101519. doi: 10.1016/j.aohep.2024.101519. Epub 2024 Jun 10.

  PMID: 38866366 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood plasma

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular; Liver Cirrhosis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Petr Hříbek, MD

CONTACT

973203028; petr.hribek@uvn.cz

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 6, 2020
• First Posted: January 9, 2020
• Study Start: October 1, 2017
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2022
• Last Updated: January 13, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)