- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03356457
Development of Agents to Diminish the Risk of Hypoglycemia-induced Brain Injury in Type 1 Diabetes
January 20, 2021 updated by: Yale University
To determine the effect of re-activation of brain glucose metabolism induced by dichloroacetate (DCA) on cognitive function and counterregulatory hormone responses in patients with type 1 diabetes (T1DM) with recurrent hypoglycemia.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This will be a single center, placebo-controlled, cross-over, randomized clinical pilot study.
The screening will take place at the Yale New Haven Hospital Research Unit (HRU) 10th floor, East Pavilion at 20 York St., New Haven, CT.
At the screening visit informed consent will be obtained.
Medical history and documents will be reviewed to screen potential subjects by inclusion and exclusion criteria.
Subjects will receive a physical examination and laboratory blood work (BUN/creatinine, electrolytes, lipid profile, liver function, and HbA1c) as well as urine toxicology screens (to confirm self-report of alcohol, and drug information) to ensure good physical health.
Study Type
Interventional
Enrollment (Actual)
21
Phase
- Early Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Connecticut
-
New Haven, Connecticut, United States, 06510
- Yale New Haven Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
Group 1:
- Diagnosed C-peptide-negative T1DM, > 5 years duration, HbA1c of < 7.5%
- Intensive management, defined by frequent self-monitoring of glucose values and by the administration of 3 or more insulin injections each day (or the use of insulin pump therapy).
- History of severe hypoglycemia and hypoglycemia unawareness as assessed by the Guy's and Thomas' Minimally Modified Clarke Hypoglycemia Survey, the Gold Score and the Edinburgh Hypoglycemia Survey (see Appendix 1)
- Willingness to fast and to reduce insulin therapy for a limited time period
Group 2:
- Age, weight, and gender matched to group 1 subjects
- HbA1c <6%
- Good general health as evidenced by medical history and blood screening
- Willing to fast for a limited time period
Exclusion Criteria:
General criteria:
- Known allergic reactions to components of the study product(s)
- Participants carrying polymorphisms known to slow DCA metabolism (e.g. KGM or EGM allele [10])
- Treatment with another investigational drug or other intervention
- Active infection including hepatitis C, hepatitis B, HIV
- Any past or current history of alcohol or substance abuse
- Psychiatric or neurological disorders, including need for medications, including anxiolytics, and antidepressants
- Baseline Hgb < 10.5 g/dL in females, or < 12.5 g/dL in males. Blood donation within 30 days of the study
- History of coagulopathy or medical condition requiring long-term anticoagulant therapy (low-dose aspirin treatment is allowed)
- Co-existing cardiac, liver, and kidney disease
- Abnormal liver function tests
- GI disorders potentially interfering with the ability to absorb oral medications
- Women that are post-menopausal, pregnant (as assessed by pregnancy test that will be performed on female participants at reproductive age), or lactating.
- Any medical condition that, in the opinion of the investigators, will interfere with the safe completion of the study or study outcomes
- Any medication assumed less than 30 days before the study sessions that, in the opinion of the investigators, will interfere with the safe completion of the study or study outcomes.The list of medications to be avoided includes - but is not limited to - drugs known to influence metabolic and endocrine function (other than insulin in Group 1) and neuroactive medications.
Group 1:
- Detectable C-peptide;
- Untreated proliferative retinopathy;
- Creatinine ≥1.5 mg/dl, urinary albumin levels . 300 mg/day
- Autonomic neuropathy; painful peripheral neuropathy
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: DCA in T1DM with severe hypoglycemia
12 T1DM subjects (C-peptide negative, HbA1c <7.5%) with a history of severe hypoglycemia and hypoglycemia unawareness as assessed by the Guy's and Thomas' Minimally Modified Clarke Hypoglycemia Survey, the Gold Score and the Edinburgh Hypoglycemia Survey and as evidenced by interview and glucose log and/or continuous glucose monitoring will receive a single dose of 12.5mg/kg dichloroacetate (DCA).
|
Dichloroacetate is an isoform-unspecific inhibitor of four regulatory pyruvate dehydrogenase kinases, which are able to reduce entry of substrates into mitochondria by reducing the conversion of pyruvate to acetyl-CoA.
Drug will be administered to subjects with sever hypoglycemia as well as healthy non-diabetic subjects.
Other Names:
|
Placebo Comparator: Placebo in T1DM with severe hypoglycemia
12 T1DM subjects (C-peptide negative, HbA1c <7.5%) with a history of severe hypoglycemia and hypoglycemia unawareness as assessed by the Guy's and Thomas' Minimally Modified Clarke Hypoglycemia Survey, the Gold Score and the Edinburgh Hypoglycemia Survey and as evidenced by interview and glucose log and/or continuous glucose monitoring will receive a placebo oral capsule.
|
A Placebo oral capsule identical in shape and color to those with active ingredient.
Other Names:
|
Active Comparator: DCA in healthy control subjects
12 non-diabetic healthy subjects (fasting plasma glucose < 100 mg/dL, HbA1c < 6.0%), who are matched for age, gender, and weight to T1DM subjects, to serve as controls for the study.
Each subject will receive a single dose of 12.5mg/kg dichloroacetate (DCA).
|
Dichloroacetate is an isoform-unspecific inhibitor of four regulatory pyruvate dehydrogenase kinases, which are able to reduce entry of substrates into mitochondria by reducing the conversion of pyruvate to acetyl-CoA.
Drug will be administered to subjects with sever hypoglycemia as well as healthy non-diabetic subjects.
Other Names:
|
Placebo Comparator: Placebo in healthy control subjects
12 non-diabetic healthy subjects (fasting plasma glucose < 100 mg/dL, HbA1c < 6.0%), who are matched for age, gender, and weight to T1DM subjects, to serve as controls for the study will receive a placebo oral capsule.
|
A Placebo oral capsule identical in shape and color to those with active ingredient.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
• Measurement of hormone changes during hypoglycemia
Time Frame: 1 day
|
Plasma counterregulatory hormone concentrations will be collected during the controlled insulin-induced hypoglycemic portion of the study.
|
1 day
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
cognitive function
Time Frame: 1 day
|
Performance on a battery of cognitive tests assessing short term memory during controlled hypoglycemia.
The Cantab battery of short-term memory tests will be used.
|
1 day
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 30, 2017
Primary Completion (Actual)
March 20, 2019
Study Completion (Actual)
March 20, 2019
Study Registration Dates
First Submitted
November 9, 2017
First Submitted That Met QC Criteria
November 22, 2017
First Posted (Actual)
November 29, 2017
Study Record Updates
Last Update Posted (Actual)
January 22, 2021
Last Update Submitted That Met QC Criteria
January 20, 2021
Last Verified
January 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2000029203
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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