Type1 Diabetes MellitusEarly Phase 1NCT03738852
Mechanisms for Restoration of Hypoglycemia Awareness
A Early Phase 1 study testing Continuous Glucose Monitor (CGM) and Insulin in people with Type1 Diabetes Mellitus, run by Yale University at 1 site in United States.
Trial summary
To assess if using the hypoglycemic clamp and functional magnetic resonance imaging (fMRI) scanning in hypoglycemia unaware and aware T1DM patients and healthy controls have showed distinct differences in patterns of brain responses. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Type1 Diabetes Mellitus
- What is being tested?
- Continuous Glucose Monitor (CGM) and Insulin
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Nov 2018to 14 Aug 2023
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Ages > 18 years
- Healthy, non-diabetic control or T1DM
- BMI > 18.0
Who cannot join
- Creatinine > 1.5 mg/dL
- Hct < 35% for females, < 39% for males
- ALT > 2.5 X ULN
- untreated thyroid disease
- uncontrolled hypertension
- neurologic disorders
Show all 15Show fewer
- untreated depression or change in antidepressant regimen in last 3 months
- use of any anxiolytic medications (benzodiazepine) or antipsychotic medications
- greater than 5% change in weight in last 3 months
- malignancy
- current or recent steroid use in last 3 months
- illicit drug use
- significant complications related to diabetes (peripheral neuropathy, proliferative retinopathy)
- inability to enter MRI (per standard MRI safety guidelines)
- for women: pregnancy or breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale Center for Clinical Investigation (YCCI) Church Street Research Unit (CSRU)
New Haven, Connecticut, 06519
About this study
To assess if using the hypoglycemic clamp and functional magnetic resonance imaging (fMRI) scanning in hypoglycemia unaware and aware T1DM patients and healthy controls have showed distinct differences in patterns of brain responses. In particular, T1DM patients who are aware of hypoglycemia (T1DM-Aware) have greater activity in sensory integration brain regions (e.g. parietal lobe and caudate nucleus) in response to hypoglycemia, whereas hypoglycemia unaware T1DM patients (T1DM-Unaware) show no detectable changes in brain reward regions during hypoglycemia.
Read the detailed description
To assess the following: 1) if these differences are driven purely by recurrent hypoglycemia or by other closely linked factors (e.g. glycemic variability); 2) the molecular and metabolic mechanisms by which unawareness leads to the suppression of central nervous system (CNS) activity in the context of hypoglycemia; and 3) whether hypoglycemia avoidance using continuous glucose monitor restores central nervous system (CNS) activation and metabolism toward normal levels and offers a therapeutic approach to more effectively combat neurocognitive dysfunction associated with intensive treatment of T1DM patients.
- Conditions
- Type1 Diabetes Mellitus
- Being tested
- Continuous Glucose Monitor (CGM), Insulin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuous Glucose Monitor (CGM)Device
Also called Dexcom G6
Continuous Glucose Monitor (CGM)
InsulinDrug
standard insulin regimen
| Study group | Role | What they receive |
|---|---|---|
| Aim 3: Type 1 diabetes mellitus user unaware subjects 3 months | Experimental | Continuous Glucose Monitor for 3 months duration Receives: Device: Continuous Glucose Monitor (CGM); Drug: Insulin |
| Aim 1: Impact of hypoglycemia on brain connectivity Type 1 | Experimental | Healthy controls, T1 aware, and T1 unawares Receives: Drug: Insulin |
| Aim 2: Impact of hypoglycemia on brain glucose transports in Type 1 | Experimental | Healthy controls, T1 aware, and T1 unawares Receives: Drug: Insulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brain Glucose Levels
Regional quantification of brain glucose levels with MRS (CMRgl) will be used to measure group differences.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2018
- Study start7 Nov 2018
- Primary completion14 Aug 2023
- Study completion14 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type1 Diabetes MellitusStudies 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
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Janice Hwang, Hwang, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03738852
- Sponsor's protocol ID
- 2000023189
- Other IDs
- 2R01DK020495-42
- Status last verified
- Jan 2025
- First submitted
- 8 Nov 2018
- Last updated
- 12 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
Akingbesote ND, Leitner BP, Jovin DG, Desrouleaux R, Owusu D, Zhu W, Li Z, Pollak MN, Perry RJ. Gene and protein expression and metabolic flux analysis reveals metabolic scaling in liver ex vivo and in vivo. Elife. 2023 May 23;12:e78335. doi: 10.7554/eLife.78335.
PubMed 37219930
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms for Restoration of Hypoglycemia Awareness
- ClinicalTrials.gov ID
- NCT03738852
- Acronym / sponsor ID
- 2000023189
- Conditions
- Type1 Diabetes Mellitus
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 7 Nov 2018 (actual)
- Primary completion
- 14 Aug 2023 (actual)
- Study completion
- 14 Aug 2023 (actual)
- First posted
- 13 Nov 2018 (actual)
- Results
- Posted 12 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess if using the hypoglycemic clamp and functional magnetic resonance imaging (fMRI) scanning in hypoglycemia unaware and aware T1DM patients and healthy controls have showed distinct differences in patterns of brain responses. In particular, T1DM patients who are aware of hypoglycemia (T1DM-Aware) have greater activity in sensory integration brain regions (e.g. parietal lobe and caudate nucleus) in response to hypoglycemia, whereas hypoglycemia unaware T1DM patients (T1DM-Unaware) show no detectable changes in brain reward regions during hypoglycemia.
Detailed description
To assess the following: 1) if these differences are driven purely by recurrent hypoglycemia or by other closely linked factors (e.g. glycemic variability); 2) the molecular and metabolic mechanisms by which unawareness leads to the suppression of central nervous system (CNS) activity in the context of hypoglycemia; and 3) whether hypoglycemia avoidance using continuous glucose monitor restores central nervous system (CNS) activation and metabolism toward normal levels and offers a therapeutic approach to more effectively combat neurocognitive dysfunction associated with intensive treatment of T1DM patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Aim 3: Type 1 diabetes mellitus user unaware subjects 3 months | Experimental | Device: Continuous Glucose Monitor (CGM), Drug: InsulinContinuous Glucose Monitor for 3 months duration |
| Aim 1: Impact of hypoglycemia on brain connectivity Type 1 | Experimental | Drug: InsulinHealthy controls, T1 aware, and T1 unawares |
| Aim 2: Impact of hypoglycemia on brain glucose transports in Type 1 | Experimental | Drug: InsulinHealthy controls, T1 aware, and T1 unawares |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Ages > 18 years
- Healthy, non-diabetic control or T1DM
- BMI > 18.0
Key exclusion criteria (15 listed)
- Creatinine > 1.5 mg/dL
- Hct < 35% for females, < 39% for males
- ALT > 2.5 X ULN
- untreated thyroid disease
- uncontrolled hypertension
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 |
|---|---|---|
| Continuous Glucose Monitor (CGM)Also: Dexcom G6Continuous Glucose Monitor (CGM) | Device | Aim 3: Type 1 diabetes mellitus user unaware subjects 3 months |
| Insulinstandard insulin regimen | Drug | Aim 1: Impact of hypoglycemia on brain connectivity Type 1, Aim 2: Impact of hypoglycemia on brain glucose transports in Type 1, Aim 3: Type 1 diabetes mellitus user unaware subjects 3 months |
Primary outcome
Brain Glucose Levels
Time frame: 3 months
Regional quantification of brain glucose levels with MRS (CMRgl) will be used to measure group differences.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37219930Akingbesote ND, Leitner BP, Jovin DG, Desrouleaux R, Owusu D, Zhu W, Li Z, Pollak MN, Perry RJ. Gene and protein expression and metabolic flux analysis reveals metabolic scaling in liver ex vivo and in vivo. Elife. 2023 May 23;12:e78335. doi: 10.7554/eLife.78335.
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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.
Janice Hwang, Hwang 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 Continuous Glucose Monitor (CGM) and Insulin in people with Type1 Diabetes Mellitus, 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 3 inclusion and 15 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 12 Feb 2025. 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. 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?
Yes. Results are posted in the registry (first posted 12 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Brain Glucose Levels (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03738852, which also lists 1 linked publication.
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 12 Feb 2025.