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Metabolic Effects of Chemical Interactions in Toxicity

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00253773
First Posted: November 15, 2005
Last Update Posted: January 13, 2010
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  Purpose
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.

Condition Intervention
Oxidative Stress Drug: acetominophen, sulfer amino acids; cysteine and methionine

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single
Primary Purpose: Diagnostic
Official Title: Metabolic Effects of Chemical Interactions in Toxicity

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • individual thiol and disulfide components; GSH/GSSG and Cys/CySS redox state; urinary output of taurine and sulfate

Estimated Enrollment: 15
Study Start Date: January 2005
Study Completion Date: November 2007
Detailed Description:
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.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

healthy volunteers males and females

Exclusion Criteria:

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

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00253773


Locations
United States, Georgia
Emory University Hospital
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Dean Jones, Ph.D. Emory University
  More Information

ClinicalTrials.gov Identifier: NCT00253773     History of Changes
Other Study ID Numbers: ES12929 (completed)
DK66008
First Submitted: November 14, 2005
First Posted: November 15, 2005
Last Update Posted: January 13, 2010
Last Verified: January 2010

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
sulfer amino acids
redox status

Additional relevant MeSH terms:
Acetaminophen
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics