Metabolic Effects of Chemical Interactions in Toxicity

Oxidative Stress Clinical Trial

Official title:

Metabolic Effects of Chemical Interactions in Toxicity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00253773
• Other study ID #: ES12929 (completed)
• Secondary ID: DK66008
• Status: Completed
• Phase: N/A
• First received: November 14, 2005
• Last updated: January 12, 2010
• Start date: January 2005
• Est. completion date: November 2007

Study information

• Verified date: January 2010
• Source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: November 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

healthy volunteers males and females

Exclusion Criteria:

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Oxidative Stress

Intervention

Drug:
• acetominophen, sulfer amino acids; cysteine and methionine

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	individual thiol and disulfide components; GSH/GSSG and Cys/CySS redox state; urinary output of taurine and sulfate