Regulation of Brain Glucose Metabolism in Type 1 Diabetes

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 1; Hypoglycemia Unawareness
• Intervention / Treatment: Drug: Dichloroacetate

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 Type: Interventional
• Enrollment (Estimated): 16
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Alice Hahn; Phone Number: 4753210504; Email: alice.hahn@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale-New Haven Hospital
      • Contact: Alice Hahn Clinical Research Coordinator; Phone Number: 5163052961; Email: alice.hahn@yale.edu
      • Principal Investigator: Raimund Herzog

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; oral solution with flavoring agent, no active drug.	Drug: Dichloroacetate; 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.; Other Names: DCA
Active Comparator: Dichloroacetate; oral solution of dichloroacetate with flavoring agent	Drug: Dichloroacetate; 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.; Other Names: DCA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Function	Measures of reaction time [in milliseconds] and cognitive testing performance under hypoglycemia [percentage].	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain glucose metabolism	Measurement of brain glucose metabolism under hypoglycemia.	1 day

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Raimund Herzog, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: March 30, 2022
• First Submitted That Met QC Criteria: March 30, 2022
• First Posted (Actual): April 7, 2022

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: June 30, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Hypoglycemia; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 2000035036

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Grouped analysis will be made available after the completion of the study within one year after completion of enrollment at the most.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication.

IPD Sharing Access Criteria

Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.

For individual participant data meta-analysis

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No