Glutathione Metabolism in Adolescents With Type 1 Diabetes - Study B

NCT ID: NCT00858273

Last Updated: 2023-05-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2011-08-31

Brief Summary

Glutathione is normally present at high levels in the blood and plays an important role in the body's defense against oxidative stress, that is, against the damage caused to the body by several 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 the blood depends on the balance between its rate of synthesis and its rate of use.

In earlier studies, we found that in poorly controlled diabetic teenagers, glutathione was low, not because it was not produced fast enough, but because it was used at an excessive rate. In this study, we want to find out whether improving blood sugar control will increase glutathione levels, and, if so, how long this will take. We also hope to find out if oral supplementation with a mixture of several antioxidant vitamins and minerals will increase glutathione levels more than taking a placebo.

Detailed Description

Forty adolescents with T1D will undergo a measurement of blood glutathione concentration and markers of oxidative stress (plasma protein-bound 3-nitrotyrosine, and urinary 8OH-2-dG, and F2-isoprostane excretion, markers of oxidative damage to protein, DNA and lipids, respectively) while at near normoglycemia, on two separate occasions:

• first, when in poor glucose control (HbA1c>7.5%); and
• secondly, after 3 to 9 months months of improved blood glucose control, along with the administration of either a placebo, or a mixture of antioxidant minerals and vitamins based on a randomization scheme.

Between the two metabolic study days, patients will receive the same intensified diabetes regimen consisting of education and counseling, home blood glucose monitoring, multiple daily insulin injections (MDI), diet plan, and frequent phone contact with a certified diabetes educator.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Antioxidant Supplement

Vitamin C 250 mg; beta-carotene 6 mg; vitamin E 30 mg; selenium 100 mcg; zinc 20 mg

Group Type: ACTIVE_COMPARATOR

Antioxidant supplement

Intervention Type: DIETARY_SUPPLEMENT

1 capsule daily with dinner

Diabetes treatment

Intervention Type: OTHER

Intensification of diabetes treatment regimen, including education and counseling, home blood glucose monitoring, multiple daily insulin injections (MDI), diet plan, and frequent phone contact with a certified diabetes educator

Regular Insulin

Intervention Type: DRUG

Regular Insulin, IV, to maintain blood glucose in normoglycemic range (70-140) during metabolic study

Placebo

Group Type: PLACEBO_COMPARATOR

Antioxidant supplement

Intervention Type: DIETARY_SUPPLEMENT

1 capsule daily with dinner

Diabetes treatment

Intervention Type: OTHER

Intensification of diabetes treatment regimen, including education and counseling, home blood glucose monitoring, multiple daily insulin injections (MDI), diet plan, and frequent phone contact with a certified diabetes educator

Regular Insulin

Intervention Type: DRUG

Regular Insulin, IV, to maintain blood glucose in normoglycemic range (70-140) during metabolic study

Interventions

Antioxidant supplement

1 capsule daily with dinner

Intervention Type: DIETARY_SUPPLEMENT

Diabetes treatment

Intensification of diabetes treatment regimen, including education and counseling, home blood glucose monitoring, multiple daily insulin injections (MDI), diet plan, and frequent phone contact with a certified diabetes educator

Intervention Type: OTHER

Regular Insulin

Regular Insulin, IV, to maintain blood glucose in normoglycemic range (70-140) during metabolic study

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 12-21
• 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: 12 Years
• Maximum Eligible Age: 21 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

Responsibility Role: SPONSOR

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

References

Benson M, Hossain J, Darmaun D. Improved glycemic control either alone, or combined with antioxidant supplementation, fails to restore blood glutathione or markers of oxidative stress in adolescents with poorly controlled type 1 diabetes. Nutr Res. 2023 Sep;117:83-90. doi: 10.1016/j.nutres.2023.05.010. Epub 2023 May 25.

Reference Type: DERIVED

PMID: 37515943 (View on PubMed)

Other Identifiers

JDRF 1-2006-627-B

Identifier Type: -

Identifier Source: org_study_id