Glutathione Metabolism in Adolescents With Type 1 Diabetes - Study A

NCT ID: NCT00858897

Last Updated: 2023-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2009-02-28

Brief Summary

Glutathione is normally present at high (millimolar) levels in blood and plays an important role in the body's defense against oxidative stress, that is, against the damage caused to the body by reactive oxygen species produced by the metabolism of most nutrients, including glucose. Glutathione is a small peptide made from 3 amino acids, glutamate, cysteine, and glycine.

This study is looking at how blood sugar levels may affect the way glutathione is made and used by the body. Since glutathione is continuously synthesized and broken down, the amount of glutathione present in blood depends on the balance between its rate of synthesis and its rate of use.

In earlier studies, the investigators found that in poorly controlled diabetic teenagers, glutathione was low, not because its production was decreased, but because it was used at an excessive rate. In this study, the investigators want to determine how short-term changes in blood sugar levels affect glutathione levels. This will help improve our understanding of how diabetes affects metabolism.

Detailed Description

Adolescents with uncomplicated T1D will receive two, 5-hour infusions of deuterium-labeled cysteine on 2 separate days, a few weeks apart, while blood glucose will be maintained, using intravenous insulin infusion:

• in the hyper-glycemic range (200-250 mg/dL) on one study day, and
• near normoglycemia (80-140 mg/dL) on the other study day.

The order of the study days will be randomized.

We will determine whether the level of blood glucose at the time of study affects blood glutathione concentration, and, if so, whether this is associated with changes in the fractional rate of glutathione synthesis, as determined from the incorporation of labeled cysteine into blood glutathione over the course of the 5-hr infusion of labeled cysteine.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Normoglycemia

80-140 mg/dL

Group Type: EXPERIMENTAL

Cysteine isotope infusion at normoglycemia vs hyperglycemia

Intervention Type: OTHER

L-\[3,3-2H2\]cysteine

Regular Insulin

Intervention Type: DRUG

Regular insulin, IV, as needed to maintain blood glucose in near-normoglycemic range (80-140 mg/dL) or hyperglycemic range (200-250 mg/mL) during metabolic studies

Hyperglycemia

200-250 mg/dL

Group Type: EXPERIMENTAL

Cysteine isotope infusion at normoglycemia vs hyperglycemia

Intervention Type: OTHER

L-\[3,3-2H2\]cysteine

Regular Insulin

Intervention Type: DRUG

Regular insulin, IV, as needed to maintain blood glucose in near-normoglycemic range (80-140 mg/dL) or hyperglycemic range (200-250 mg/mL) during metabolic studies

Interventions

Cysteine isotope infusion at normoglycemia vs hyperglycemia

L-\[3,3-2H2\]cysteine

Intervention Type: OTHER

Regular Insulin

Regular insulin, IV, as needed to maintain blood glucose in near-normoglycemic range (80-140 mg/dL) or hyperglycemic range (200-250 mg/mL) during metabolic studies

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Type 1 diabetes, using usual criteria such as: glycosuria, hyperglycemia prior to treatment
• BMI <25 kg/m2
• Age 14-18
• HbA1c>7.5%
• No evidence of diabetic complications
• Written informed consent from parents or legal guardian, and assent from patient

Exclusion Criteria

• Presence of significant anemia (hemoglobin <11g/dL)
• Presence of intercurrent illness such as infection
• Presence of chronic disease such as other endocrine deficiency, chronic respiratory or cardiac disease
• Chronic use of medication other than insulin
• Use of vitamin or mineral supplements within 2 weeks of study

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role: collaborator

Nemours Children's Clinic

OTHER

Sponsor Role: lead

Responsible Party

Dominique Darmaun

Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dominique Darmaun, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Nemours Children's Clinic

Locations

Nemours Children's Clinic

Jacksonville, Florida, United States

Countries

United States

Other Identifiers

JDRF 1-2006-627-A

Identifier Type: -

Identifier Source: org_study_id