Regulation of Brain Glucose Metabolism in Type 1 Diabetes

• Status: Not yet recruiting
• Trial end date: 2023-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a prospective randomized placebo-controlled double-blind crossover study determining the effect of dichloroacetate on brain glucose metabolism under clamped hypoglycemia in T1DM.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Yale University

Criteria

Inclusion Criteria:

T1DM subjects (C-peptide negative) with a history of severe hypoglycemia and/or hypoglycemia unawareness. All enrolled T1DM subjects will be randomized to undergo two research session with either placebo and DCA administration 30 minutes prior to clamp with deuterium metabolic imaging by NMR under clamped hypoglycemia. All subjects will meet the detailed inclusion and exclusion criteria outlined below. T1DM subjects must demonstrate:

1. A history of severe hypoglycemia, requiring the assistance of another person with a blood glucose <54 mg/dL or prompt recovery after the administration of oral carbohydrate, intravenous glucose, or glucagon).

2. At least 2 values <54mg/dl during 2 weeks of CGMS testing during the week prior to study.

3. Reduced awareness of hypoglycemia (defined by hypoglycemia and awareness questionnaire)

Exclusion Criteria:

Age < 18 years or >55 years. Body weight >85 kg at screening visit BMI > 30 (female) and >30 (male) kg/m2. Detectable C-peptide level Untreated proliferative retinopathy Carriers of glutathione transferase Z1 (GSTZ-1) gene polymorphisms that predispose for DCA accumulation and toxicity