Diabetes Mellitus, Type 1, Hypoglycemia Unawareness
Conditions
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.
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.
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Function | 1 day | Measures of reaction time \[in milliseconds\] and cognitive testing performance under hypoglycemia \[percentage\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brain glucose metabolism | 1 day | Measurement of brain glucose metabolism under hypoglycemia. |
Countries
United States
Contacts
Primary ContactAlice Hahn
Outcome results
None listed