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| Name | Class |
|---|---|
| Juvenile Diabetes Research Foundation | OTHER |
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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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normoglycemia | Experimental | 80-140 mg/dL |
|
| Hyperglycemia | Experimental | 200-250 mg/dL |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cysteine isotope infusion at normoglycemia vs hyperglycemia | Other | L-[3,3-2H2]cysteine |
|
| Measure | Description | Time Frame |
|---|---|---|
| Glutathione Concentration | umol/L | Up to 30 minutes post- 5 hour infusion on Day 1 (First Intervention) and up to 30 minutes post- 5 hour infusion on Day 14 (Second Intervention) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dominique Darmaun, MD, PhD | Nemours Children's Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nemours Children's Clinic | Jacksonville | Florida | 32207 | United States |
Each of the 10 Subjects received two 5-hour intravenous infusions of L-[3,3-2H2]cysteine in the postabsorptive state on 2 separate days after blood glucose had been maintained overnight at normoglycemia or hyperglycemia, using intravenous insulin infusion. The order of the normo- and hyper-glycemia study days was randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | Normoglycemia (80-140 mg/dL), Then Hyperglycemia (200-250 mg/dL) | Cysteine isotope infusion at normoglycemia vs hyperglycemia: L-[3,3-2H2]cysteine on 2 separate days, in randomized order Regular Insulin: Regular insulin, IV, as needed to maintain blood glucose in near-normoglycemic range (80-140 mg/dL) during metabolic studies |
| FG001 | Hyperglycemia (200-250 mg/dL), Then Normoglycemia (80-140 mg/dL) | Cysteine isotope infusion at normoglycemia vs hyperglycemia: L-[3,3-2H2]cysteine on 2 separate days, in randomized order Regular Insulin: Regular insulin, IV, as needed to maintain blood glucose in near-normoglycemic range (80-140 mg/dL) during metabolic studies |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (1 Day) |
| |||||||||||||
| Washout (~9 Days) |
| |||||||||||||
| 2nd Intervention (1 Day) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Subjects Enrolled | Adolescents with Type 1 Diabetes |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Glutathione Concentration | umol/L | Each of the 10 Subjects received two 5-hour intravenous infusions of L-[3,3-2H2]cysteine in the postabsorptive state on 2 separate days after blood glucose had been maintained overnight at normoglycemia or hyperglycemia, using intravenous insulin infusion. | Posted | Mean | Standard Error | umol/L | Up to 30 minutes post- 5 hour infusion on Day 1 (First Intervention) and up to 30 minutes post- 5 hour infusion on Day 14 (Second Intervention) |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Normoglycemia (80-140 mg/dL) | Cysteine isotope infusion at normoglycemia vs hyperglycemia: L-[3,3-2H2]cysteine Regular Insulin: Regular insulin, IV, as needed to maintain blood glucose in near-normoglycemic range (80-140 mg/dL) during metabolic studies. Each of the 10 Subjects received two 5-hour intravenous infusions on 2 separate days after blood glucose had been maintained overnight at normoglycemia or hyperglycemia, using intravenous insulin infusion. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Dominique Darmaun | Nemours Children's Clinic | 904-697-3863 | ddarmaun@nemours.org |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D007328 | Insulin |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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| Regular Insulin | 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 |
|
| NOT COMPLETED |
|
| NOT COMPLETED |
|
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| HbA1C | percent of total hemoglobin, reflecting average blood glucose control over the previous 3- to 6-month period | Mean | Standard Deviation | percent of total hemoglobin |
|
| Hyperglycemia (200-250 mg/dL) |
Cysteine isotope infusion at normoglycemia vs hyperglycemia: L-[3,3-2H2]cysteine 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 |
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | Hyperglycemia (200-250 mg/dL) | Cysteine isotope infusion at normoglycemia vs hyperglycemia: L-[3,3-2H2]cysteine Regular Insulin: Regular insulin, IV, as needed to maintain blood glucose in hyperglycemic range (200-250 mg/mL) during metabolic studies. Each of the 10 Subjects received two 5-hour intravenous infusions on 2 separate days after blood glucose had been maintained overnight at normoglycemia or hyperglycemia, using intravenous insulin infusion. | 0 | 10 | 0 | 10 | 0 | 10 |
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| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |