Hyperglycaemia (Diabetic)Early Phase 1NCT03356457
Development of Agents to Diminish the Risk of Hypoglycemia-induced Brain Injury in Type 1 Diabetes
A Early Phase 1 study testing Dichloroacetate in people with Hyperglycaemia (Diabetic), run by Yale University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hyperglycaemia (Diabetic)
- What is being tested?
- Dichloroacetate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2017to 20 Mar 2019
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale New Haven Hospital
New Haven, Connecticut, 06510
About this study
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.
Read the 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.
- Conditions
- Hyperglycaemia (Diabetic)
- Being tested
- Dichloroacetate, Placebo oral capsule
- Medical subject headings
- Hyperglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DichloroacetateDrug
Also called 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.
Placebo oral capsuleDrug
Also called Placebo
A Placebo oral capsule identical in shape and color to those with active ingredient.
| Study group | Role | What they receive |
|---|---|---|
| DCA in T1DM with severe hypoglycemia | Active comparator | 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). Receives: Drug: Dichloroacetate |
| Placebo in T1DM with severe hypoglycemia | Placebo comparator | 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. Receives: Drug: Placebo oral capsule |
| DCA in healthy control subjects | Active comparator | 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). Receives: Drug: Dichloroacetate |
| Placebo in healthy control subjects | Placebo comparator | 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. Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
• Measurement of hormone changes during hypoglycemia
Plasma counterregulatory hormone concentrations will be collected during the controlled insulin-induced hypoglycemic portion of the study.
Measured: 1 day
Secondary outcomes (1)
cognitive function
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.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2017
- Study start30 Nov 2017
- Primary completion20 Mar 2019
- Study completion20 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hyperglycaemia (Diabetic)Studies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This will be a single center, placebo-controlled, cross-over, randomized clinical pilot study. 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.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Raimund Herzog, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03356457
- Sponsor's protocol ID
- 2000029203
- Status last verified
- Jan 2021
- First submitted
- 9 Nov 2017
- Last updated
- 22 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of Agents to Diminish the Risk of Hypoglycemia-induced Brain Injury in Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT03356457
- Acronym / sponsor ID
- 2000029203
- Conditions
- Hyperglycaemia (Diabetic)
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 30 Nov 2017 (actual)
- Primary completion
- 20 Mar 2019 (actual)
- Study completion
- 20 Mar 2019 (actual)
- First posted
- 29 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 4
- Model description
- This will be a single center, placebo-controlled, cross-over, randomized clinical pilot study. 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.
| Arm | Type | Receives |
|---|---|---|
| DCA in T1DM with severe hypoglycemia | Active comparator | Drug: Dichloroacetate12 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). |
| Placebo in T1DM with severe hypoglycemia | Placebo comparator | Drug: Placebo oral capsule12 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. |
| DCA in healthy control subjects | Active comparator | Drug: Dichloroacetate12 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). |
| Placebo in healthy control subjects | Placebo comparator | Drug: Placebo oral capsule12 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
- Age, weight, and gender matched to group 1 subjects
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DichloroacetateAlso: DCADichloroacetate 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. | Drug | DCA in T1DM with severe hypoglycemia, DCA in healthy control subjects |
| Placebo oral capsuleAlso: PlaceboA Placebo oral capsule identical in shape and color to those with active ingredient. | Drug | Placebo in T1DM with severe hypoglycemia, Placebo in healthy control subjects |
Primary outcome
• 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 secondary outcome
cognitive function
Time frame: 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raimund Herzog, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Dichloroacetate in people with Hyperglycaemia (Diabetic), run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
• Measurement of hormone changes during hypoglycemia (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2021.