2,3,7,8-Tetrachlorodibenzo-Para-Dioxin (TCDD) Exposure Clinical Trial
Official title:
Molecular Epidemiology of Dioxin-Related Illness in Seveso
Verified date | April 2020 |
Source | National Institutes of Health Clinical Center (CC) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
In 1976 an accidental explosion in a chemical plant 16 miles north of Milan resulted in
contamination of the local population with 2, 3, 7, 8-terachlorodibenzo-para-dioxin (TCDD).
There is evidence that TCDD and related phenoxy herbicides act as teratogens, tumor
promoters, and carcinogens in experimental animals. In human, TCDD causes chloracne in those
exposed. Associations with various cancers have been reported, but the precise role in human
toxicity, immune and reproductive dysfunction, and cancer is controversial.
The Seveso accident provides a unique opportunity for an epidemiological investigation in
that the exposures are the highest recorded in humans, the exposure involves TCDD without
other contaminants, and a cohort in the involved and surrounding area has been enumerated.
There is inter-individual variation in the action of genes involved in TCDD effect in human
cells. The quality of human AH receptor, and the CYP1A1 and arnt genotypes are examples of
susceptibility markers that may identify subjects at high risk for TCDD-related disease. A
hypothesis that could explain the inconsistent association of TCDD exposure with cancer is
that genetic susceptibility may influence which individuals are adversely affected by TCDD
exposure.
The study is proceeding in three phases. The first is a pilot/validation study that is
complete (field activities) and involved 126 subjects. The second is a case-control study of
about 100 individuals with chloracne and 100 controls. The field components of phase one and
two are complete, and analyses of results are underway. The third and final phase is a
planned case-control study of TCDD-related cancers that will include approximately 125 cases
and 125 controls.
The study includes a questionnaire/interview and a biospecimen collection; 73 ml of blood are
obtained from each participant.
Status | Completed |
Enrollment | 300 |
Est. completion date | April 16, 2020 |
Est. primary completion date | August 13, 2007 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 100 Years |
Eligibility |
- INCLUSION CRITERIA: Subjects exposed to TCDD in the region of Lombardy, Italy. EXCLUSION CRITERIA: 1. severe medical illness: liver (cirrhosis [based on medical history], chronic or acute hepatitis [based on transaminase elevation, SGOT greater than 200 IU or SGPT greater than 200 IU]), kidney (hemo- or peritoneal dialysis dependent), cardiac (myocardial infarct in the last 6 months), AIDS (or known HIV positive), major psychiatric illness (decompensated schizophrenia); 2. IV drug abuse; 3. individuals receiving a few specific medications known to interfere with specific assays (i.e., phenobarbitol), other medication use will be recorded; 4. non-Italian origin; 5. Any condition which precludes obtaining informed consent. |
Country | Name | City | State |
---|---|---|---|
Italy | University of Milan | Milan |
Lead Sponsor | Collaborator |
---|---|
National Cancer Institute (NCI) |
Italy,
Baccarelli A, Giacomini SM, Corbetta C, Landi MT, Bonzini M, Consonni D, Grillo P, Patterson DG, Pesatori AC, Bertazzi PA. Neonatal thyroid function in Seveso 25 years after maternal exposure to dioxin. PLoS Med. 2008 Jul 29;5(7):e161. doi: 10.1371/journal.pmed.0050161. — View Citation
Consonni D, Sindaco R, Agnello L, Caporaso NE, Landi MT, Pesatori AC, Bertazzi PA. Plasma levels of dioxins, furans, non-ortho-PCBs, and TEQs in the Seveso population 17 years after the accident. Med Lav. 2012 Jul-Aug;103(4):259-67. — View Citation
McHale CM, Zhang L, Hubbard AE, Zhao X, Baccarelli A, Pesatori AC, Smith MT, Landi MT. Microarray analysis of gene expression in peripheral blood mononuclear cells from dioxin-exposed human subjects. Toxicology. 2007 Jan 5;229(1-2):101-13. Epub 2006 Oct 17. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | To determine the effect of TCDD exposure on human health | Cancer Risk | Ongoing |