Metabolic Analysis in Human Sulfur Amino Acid Deficiency

Diabetes Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00253760
• Other study ID #: R03 DK66008 (completed 2007)
• Status: Completed
• Phase: N/A
• First received: November 14, 2005
• Last updated: March 17, 2010
• Start date: February 2004
• Est. completion date: February 2007

Study information

• Verified date: March 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

Varied food intake, disease, and genetic differences result in complex diet-health interactions. In principle, information-rich metabolic analyses combined with bioinformatic tools provide an approach to explore these interactions. This project is a feasibility study of the use of high-resolution 1H-nuclear magnetic resonance (NMR) to study metabolic perturbations induced by a deficiency in sulfur amino acids (SAA). The investigators will 1) test the hypothesis that deficient dietary intake of SAA in humans results in oxidation of reduced glutathione (GSH)/oxidized glutathione (GSSG) redox and 2) determine whether 1H-NMR of blood and urine detects metabolic changes due to SAA deficiency.

Description:

Varied food intake, disease, and genetic differences result in complex diet-health interactions. In principle, information-rich metabolic analyses combined with bioinformatic tools provide an approach to explore these interactions. This project is a feasibility study of the use of high-resolution 1H-NMR to study metabolic perturbations induced by deficiency in sulfur amino acids (SAA). In cell culture, sulfur amino acid (SAA) deficiency results in substantial oxidation of glutathione (GSH) redox state. Because GSH redox affects central homeostatic and cell defense mechanisms, redox changes in vivo due to SAA deficiency could induce complex physiologic effects that are not easily predictable by more traditional metabolic analyses. We will 1) test the hypothesis that deficient dietary intake of SAA in humans results in oxidation of GSH/GSSG redox and 2) determine whether 1H-NMR of blood and urine detects metabolic changes due to SAA deficiency. Studies will be performed on 12 healthy individuals (6 males, 6 females) in the Emory General Clinical Research Center (GCRC) using a crossover design (replete, deficient, replete). Kinetic and balance studies will establish the time course and magnitude of changes in SAA and metabolites in blood and urine in response to SAA intake. Plasma GSH/GSSG and cysteine/cystine redox will be measured to determine whether variation in intake of SAA affects steady-state thiol-disulfide redox state. 1H-NMR spectra of blood and urine samples will be used to determine whether metabolic changes unrelated to the direct SAA metabolites can be detected in association with variation in SAA intake. The results will show whether variation in SAA intake is likely to affect health risks associated with thiol-disulfide redox and oxidative stress. Furthermore, because NMR analysis of biofluids can be performed with a high throughput (e.g., 300 samples/day with a flow cell), results will show whether this approach could be useful for nutritional assessment of complex metabolic effects of SAA intake.

Recruitment information / eligibility

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

Eligibility

Inclusion Criteria:

• Normal weight

• Males or females

Exclusion Criteria:

• Smokers

• Pregnancy

• Chronic illness other than hypertension

• Age less than 18 and greater than 40 years

Study Design

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

Related Conditions & MeSH terms

• Diabetes
• Heart Diseases
• Oxidative Stress

Intervention

Drug:
• dietary 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	redox state of the two central low molecular weight thiol-disulfide pools, i.e., GSH/GSSG and cysteine (Cys)/cystine (CySS)
Primary	a global metabolic spectrum detectable by H-NMR