Regulation of Brain Glucose Metabolism in Type 1 Diabetes

Early Phase 1

Recruiting

• Conditions: Hypoglycemia Unawareness; Diabetes Mellitus, Type 1
• Interventions: Drug: Dichloroacetate

• Registration Number: NCT05317455
• Lead Sponsor: Yale University

Brief 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.

Detailed 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 study that determines whether restoring brain glucose metabolism under hypoglycemia helps maintain cognitive function.

Study Timeline

• Study First Submitted: 2022-03-30
• Study First Submitted QC: 2022-03-30
• Study First Posted: 2022-04-07
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-28
• Last Update Posted: 2025-05-01
• Study Start: 2025-05-06
• Primary Completion: 2026-05-01
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 16

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Dichloroacetate	oral solution with flavoring agent, no active drug.
Dichloroacetate	Dichloroacetate	oral solution of dichloroacetate with flavoring agent

Primary Outcome Measures

Name	Time	Method
Cognitive Function	1 day	Measures of reaction time \[in milliseconds\] and cognitive testing performance under hypoglycemia \[percentage\].

Secondary Outcome Measures

Name	Time	Method
Brain glucose metabolism	1 day	Measurement of brain glucose metabolism under hypoglycemia.

Trial Locations

Locations (1)

Yale-New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States