Back to resultsRegulation 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
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 1
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
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
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
We'll reach out to this number within 24 hrs