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Regulation of Brain Glucose Metabolism in Type 1 Diabetes

Primary Purpose

Diabetes Mellitus, Type 1, Hypoglycemia Unawareness

Status
Not yet recruiting
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Dichloroacetate
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Placebo Comparator

    Active Comparator

    Arm Label

    Placebo

    Dichloroacetate

    Arm Description

    capsule with excipient only, no active drug.

    sodium salt of dichloroacetate, 1000mg

    Outcomes

    Primary Outcome Measures

    PDH flux in the frontal lobe
    Neuronal PDH flux in the frontal lobe measured by DMI of labeled glucose

    Secondary Outcome Measures

    Full Information

    First Posted
    March 30, 2022
    Last Updated
    October 13, 2023
    Sponsor
    Yale University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05317455
    Brief Title
    Regulation of Brain Glucose Metabolism in Type 1 Diabetes
    Official Title
    Regulation of Brain Glucose Metabolism in Type 1 Diabetes
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 2024 (Anticipated)
    Primary Completion Date
    May 2024 (Anticipated)
    Study Completion Date
    May 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Yale University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief 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.
    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 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Diabetes Mellitus, Type 1, Hypoglycemia Unawareness

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Early Phase 1
    Interventional Study Model
    Crossover Assignment
    Masking
    ParticipantOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    16 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    capsule with excipient only, no active drug.
    Arm Title
    Dichloroacetate
    Arm Type
    Active Comparator
    Arm Description
    sodium salt of dichloroacetate, 1000mg
    Intervention Type
    Drug
    Intervention Name(s)
    Dichloroacetate
    Other Intervention Name(s)
    DCA
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    PDH flux in the frontal lobe
    Description
    Neuronal PDH flux in the frontal lobe measured by DMI of labeled glucose
    Time Frame
    1 day

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    55 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Alice Hahn
    Phone
    4753210504
    Email
    alice.hahn@yale.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Raimund Herzog, MD
    Organizational Affiliation
    Yale School of Medicine
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing 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
    At the completion of the clinical study a summary of findings will be uploaded.
    IPD Sharing Access Criteria
    Written request needs to be submitted to the PI or his delegate.

    Learn more about this trial

    Regulation of Brain Glucose Metabolism in Type 1 Diabetes

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