Regulation of Brain Glucose Metabolism in Type 1 Diabetes

Yale University

Status and phase: Not yet enrolling; Early Phase 1

Conditions: Diabetes Mellitus, Type 1; Hypoglycemia Unawareness

Treatments: Drug: Dichloroacetate

Study type: Interventional

Funder types: Other

Identifiers

NCT05317455

Pending

Details and patient eligibility

About

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.

Full description

This study is a prospective randomized placebo-controlled double-blind crossover study designed to address the hypothesis that dichloroacetate has the ability to re-activate brain glucose metabolism under clamped hypoglycemia. The study population is comprised of intensively treated persons with T1D with frequent exposure to hypoglycemia, who have cognitive deficits under hypoglycemia that could be attributed to changes in brain glucose oxidation. The investigators will test the experimental compound DCA in a mechanistic study that determines whether brain metabolism is restored by this intervention, or whether the drug effect was primarily caused by changes in physiology outside of the brain.

Enrollment: 16 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

T1DM subjects with:

• a history of severe hypoglycemia and/or hypoglycemia unawareness or
• a history of severe hypoglycemia with a blood glucose <54 mg/dL, requiring the assistance of another person (with recovery after the administration of oral carbohydrate, intravenous glucose, or glucagon) or
• at least 2 values <54mg/dl during 2 weeks of CGMS testing during the week prior to study.

Exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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16 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

capsule with excipient only, no active drug.

Treatment:

Drug: Dichloroacetate

Dichloroacetate

Active Comparator group

Description:

sodium salt of dichloroacetate, 1000mg

Treatment:

Drug: Dichloroacetate