RecruitingEarly Phase 1NCT05317455

Regulation of Brain Glucose Metabolism in Type 1 Diabetes

Sponsor

Yale University

Enrollment

16 participants

Start Date

May 13, 2025

Study Type

INTERVENTIONAL

Conditions

Diabetes Mellitus, Type 1 Hypoglycemia Unawareness

Summary

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

Eligibility

Min Age: 18 YearsMax Age: 55 Years

Inclusion Criteria4

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 Criteria5

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

Interventions

DRUGDichloroacetate

Dichloroacetate has a long safety record of administration to humans with a rare metabolic disorder for over 40 years. It has been given orally to patients with T2DM for up to a week without any problems and other laboratory or significant clinical adverse effects were not noted. It activates mitochondrial PDH flux, a key regulator of glucose oxidation.