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Metabolic Effects of Chemical Interactions in Toxicity

This study has been completed.
Sponsor:
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00253773
First received: November 14, 2005
Last updated: January 12, 2010
Last verified: January 2010

November 14, 2005
January 12, 2010
January 2005
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individual thiol and disulfide components; GSH/GSSG and Cys/CySS redox state; urinary output of taurine and sulfate
  • 2) GSH/GSSG and Cys/CySS redox state
  • 1)individual thiol and disulfide components
  • 3) urinary output of taurine and sulfate
Complete list of historical versions of study NCT00253773 on ClinicalTrials.gov Archive Site
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Metabolic Effects of Chemical Interactions in Toxicity
Metabolic Effects of Chemical Interactions in Toxicity

This pilot study tests the feasibility of using GSH redox state and high resolution proton NMR spectroscopy (1H-NMR) to detect metabolic changes due to acetominophen and sulfur amino acid deficiency. Our central hypothesis is that the a 2-day sulfur amino acid deficiency will alter acetominophen metabolism, acetominophen will affect sulfur amino acid homeostasis, and the treatments together will alter the global metabolic profile, as measured by 1H-NMR spectroscopy.

Most occupational exposures to toxic chemicals occur in the context of complex mixtures, often in combination with varied diet, prescription drug use and disease. In principle, information-rich metabolic analyses provide an approach to study toxicologic consequences of such complex chemical interactions by revealing metabolic perturbations before irreversible injury occurs. This pilot study tests the feasibility of using GSH redox state and high resolution proton NMR spectroscopy (1H-NMR) to detect metabolic changes due to chemical interactions. The proposed model involves interaction of chemical exposure (2 doses of acetaminophen, APAP, 15 mg/kg) and 2 days of sulfur amino acid- (SAA-) free diet. 30% of APAP metabolism occurs through pathways dependent upon SAA metabolites and up to 50% of the RDA for SAA is needed to metabolize 2 doses of APAP. Both treatments are without toxicity in humans and both affect GSH homeostasis, which will be assessed in vivo by plasma measurements. Inter-individual variation will be minimized with each individual being his/her own control. Environmental and dietary influences will be controlled in a clinical research unit. Aim 1 is to determine whether SAA-free diet and APAP independently perturb GSH redox homeostasis. Aim 2 is to determine whether APAP intake interacts with SAA-free diet in affecting GSH redox state. Aim 3 is to use 1H-NMR spectroscopy to determine whether exposure to APAP and SAA-free diet interact in their effects on metabolic profile. The results will provide key data on the suitability and sensitivity of redox measurements and 1H-NMR spectroscopy for study of chemical interactions. This could provide a foundation for the use of perturbation of metabolic profile as a means to identify risks and consequences of complex chemical mixtures which would be especially relevant to occupational exposures in combination with therapeutic drugs and other health risk factors.

Interventional
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Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind
Primary Purpose: Diagnostic
Oxidative Stress
Drug: acetominophen, sulfer amino acids; cysteine and methionine
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
15
November 2007
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Inclusion Criteria:

healthy volunteers males and females

Exclusion Criteria:

acute/chronic illnesses age less than 18 and greater than 40 pregnancy

Both
18 Years to 40 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00253773
ES12929 (completed), DK66008
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: Dean Jones, Ph.D. Emory University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
January 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP