Diabetes Mellitus, Type 1NCT04387422
Recurrent Hypoglycemia in Type 1 Diabetes (Aim 2)
A study testing Experimental hyperglycemia in people with Diabetes Mellitus, Type 1, run by University of Minnesota at 1 site in United States.
Trial summary
This study will explore the cerebral mechanisms of impaired awareness of hypoglycemia (IAH) in type 1 diabetics following exposure to experimental recurrent hypoglycemia (HG). To induce IAH, patients with T1D identified to have normal awareness of hypoglycemia (NAH) will undergo three 2-hour long hypoglycemic clamps. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Experimental hyperglycemia
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Aug 2020to Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 diabetes diagnosed on clinical or laboratory grounds
- Diabetes duration 2 - 30 years
- Hemoglobin A1C <8.5%
Who cannot join
- Impaired awareness of hypoglycemia as determined by the Cox and Gold questionnaires
- Pregnant or plan to become pregnant during the study period
- Uncontrolled hypertension (blood pressure > 145/95 mmHg at screening)
- Evidence of autonomic neuropathy (presence of orthostatic hypotension or history of gastroparesis)
- Proliferative retinopathy
- Impaired kidney function (GFR < 45)
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- History of myocardial infarction, stroke, seizures, neurosurgical procedures, major depression requiring hospitalization within the last 5 years, arrhythmias
- Current substance abuse
- Use of drugs that can alter glucose metabolism including but not limited to glucocorticoids and niacin, and excluding insulin and glucose lowering drugs used to treat diabetes, as determined by a clinician
- Inability to undergo MRI scanning, including but not limited to unable to remain still in an MRI scanner for more than 30 minutes, claustrophobia, presence of paramagnetic substances or pacemakers in body, weight over 300 lbs
- Unable to complete all study visits or procedures, as determined by the investigator
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Measurement of Glucose Homeostasis in Human Brain by NMR: Effect of Recurrent Hypoglycemia on Type 1 Diabetes (Aim 2)
This study will explore the cerebral mechanisms of impaired awareness of hypoglycemia (IAH) in type 1 diabetics following exposure to experimental recurrent hypoglycemia (HG). To induce IAH, patients with T1D identified to have normal awareness of hypoglycemia (NAH) will undergo three 2-hour long hypoglycemic clamps. Neurochemical profiles will be measured by high field MRS before and after induction of IAH. Subject glycemic variability and activity/sleep for 1 week before each study will be monitored as all factors have been shown to alter responses to HG.
Read the detailed description
The long-term goal of this project is to identify how recurrent hypoglycemia (HG) leads to the clinical syndrome of impaired awareness of hypoglycemia (IAH) in type 1 diabetes (T1D).
This study will test the hypothesis that recurrent HG in T1D leads to an upregulation in brain glucose transport and alterations in glutamatergic and GABAergic tone. The investigators will use MRS methodology that permits evaluation of cerebral cortex and hypothalamus in the same session to simultaneously evaluate the cerebral correlates/mediators of impaired awareness and impaired counterregulatory hormone responses (CRR). High MR data quality and reproducibility will be ensured by using high field MR scanners and technical advances (automated voxel placement, real-time voxel position, frequency, shim updates). Continuous glucose monitoring and actigraphy will be used to chronicle glucose variability and activity/exercise/sleep in the weeks before each experiment to assess the impact of these variables on IAH.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Experimental hyperglycemia
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental hyperglycemiaOther
Experimental hyperglycemia with MRI
| Study group | Role | What they receive |
|---|---|---|
| 150 mg/dL | Experimental | Hyperglycemia target of 150 mg/dL Receives: Other: Experimental hyperglycemia |
| 225 mg/dL | Experimental | Hyperglycemia target of 225 mg/dL Receives: Other: Experimental hyperglycemia |
| 300 mg/dL | Experimental | Hyperglycemia target of 300 mg/dL Receives: Other: Experimental hyperglycemia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucose kinetics during hyperglycemic clamps before and after induction of IAH
A kinetic model of glucose transport through the blood-brain-barrier (BBB) via reversible symmetric Michaelis-Menten kinetics and irreversible utilization in brain tissue will be utilized. The kinetics of glucose transport into and utilization in the frontal cortex will be quantified using dynamic modeling to extract the Michaelis-Menten constants and the maximal rate for glucose transport and utilization. The ratio of maximal transport rate to cerebral metabolic rate of glucose will be estimated for the hypothalamus by steady-state modeling.
Measured: 240 Minutes
Secondary outcomes (6)
Antecedent glycemia concentration
Antecedent glycemia will be evaluated using continuous glucose monitors with particular attention to the percentage of time a participant is above, at, or below target of 80-180 mg/dl and to measures of glycemic variability.
Measured: 14 days
Antecedent physical activity - moderate to vigorous physical activity
Antecedent physical activity and sleep will be evaluated using the data collected by the ActiGraph Link monitors. Activity counts will be set at 15-second epochs and classified into sedentary, light, moderate, and vigorous categories based on Troiano et al. cut points. Participants' average minutes engaged in moderate to vigorous physical activity levels per day will be reported.
Measured: 14 days
Antecedent physical activity - light physical activity
Antecedent physical activity and sleep will be evaluated using the data collected by the ActiGraph Link monitors. Activity counts will be set at 15-second epochs and classified into sedentary, light, moderate, and vigorous categories based on Troiano et al. cut points. Participants' average minutes engaged in light physical activity per day will be reported.
Measured: 14 days
Antecedent physical activity - sedentary time
Antecedent physical activity and sleep will be evaluated using the data collected by the ActiGraph Link monitors. Activity counts will be set at 15-second epochs and classified into sedentary, light, moderate, and vigorous categories based on Troiano et al. cut points. Participants' average minutes engaged in sedentary time per day will be reported.
Measured: 14 days
Antecedent physical activity - energy expenditure
Antecedent physical activity and sleep will be evaluated using the data collected by the ActiGraph Link monitors. Activity counts will be set at 15-second epochs and classified into sedentary, light, moderate, and vigorous categories based on Troiano et al. cut points. Participants' average daily energy expenditure (kilocalories) will be reported.
Measured: 14 days
Antecedent physical activity - sleep quality
Antecedent physical activity and sleep will be evaluated using the data collected by the ActiGraph Link monitors. Activity counts will be set at 15-second epochs and classified into sedentary, light, moderate, and vigorous categories based on Troiano et al. cut points. Participants' average sleep quality will be reported.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2020
- Study start12 Aug 2020
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- More trials run by University of MinnesotaThe 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
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elizabeth R Seaquist, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04387422
- Sponsor's protocol ID
- MED-2019-28365
- Status last verified
- Apr 2026
- First submitted
- 31 Jan 2020
- Last updated
- 8 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Measurement of Glucose Homeostasis in Human Brain by NMR: Effect of Recurrent Hypoglycemia on Type 1 Diabetes (Aim 2)
- ClinicalTrials.gov ID
- NCT04387422
- Acronym / sponsor ID
- MED-2019-28365
- Conditions
- Diabetes Mellitus, Type 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- 12 Aug 2020 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 13 May 2020 (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.
This study will explore the cerebral mechanisms of impaired awareness of hypoglycemia (IAH) in type 1 diabetics following exposure to experimental recurrent hypoglycemia (HG). To induce IAH, patients with T1D identified to have normal awareness of hypoglycemia (NAH) will undergo three 2-hour long hypoglycemic clamps. Neurochemical profiles will be measured by high field MRS before and after induction of IAH. Subject glycemic variability and activity/sleep for 1 week before each study will be monitored as all factors have been shown to alter responses to HG.
Detailed description
The long-term goal of this project is to identify how recurrent hypoglycemia (HG) leads to the clinical syndrome of impaired awareness of hypoglycemia (IAH) in type 1 diabetes (T1D).
This study will test the hypothesis that recurrent HG in T1D leads to an upregulation in brain glucose transport and alterations in glutamatergic and GABAergic tone. The investigators will use MRS methodology that permits evaluation of cerebral cortex and hypothalamus in the same session to simultaneously evaluate the cerebral correlates/mediators of impaired awareness and impaired counterregulatory hormone responses (CRR). High MR data quality and reproducibility will be ensured by using high field MR scanners and technical advances (automated voxel placement, real-time voxel position, frequency, shim updates). Continuous glucose monitoring and actigraphy will be used to chronicle glucose variability and activity/exercise/sleep in the weeks before each experiment to assess the impact of these variables on IAH.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 150 mg/dL | Experimental | Other: Experimental hyperglycemiaHyperglycemia target of 150 mg/dL |
| 225 mg/dL | Experimental | Other: Experimental hyperglycemiaHyperglycemia target of 225 mg/dL |
| 300 mg/dL | Experimental | Other: Experimental hyperglycemiaHyperglycemia target of 300 mg/dL |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Type 1 diabetes diagnosed on clinical or laboratory grounds
- Diabetes duration 2 - 30 years
- Hemoglobin A1C <8.5%
Key exclusion criteria (11 listed)
- Impaired awareness of hypoglycemia as determined by the Cox and Gold questionnaires
- Pregnant or plan to become pregnant during the study period
- Uncontrolled hypertension (blood pressure > 145/95 mmHg at screening)
- Evidence of autonomic neuropathy (presence of orthostatic hypotension or history of gastroparesis)
- Proliferative retinopathy
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 |
|---|---|---|
| Experimental hyperglycemiaExperimental hyperglycemia with MRI | Other | 150 mg/dL, 225 mg/dL, 300 mg/dL |
Primary outcome
Glucose kinetics during hyperglycemic clamps before and after induction of IAH
Time frame: 240 Minutes
A kinetic model of glucose transport through the blood-brain-barrier (BBB) via reversible symmetric Michaelis-Menten kinetics and irreversible utilization in brain tissue will be utilized. The kinetics of glucose transport into and utilization in the frontal cortex will be quantified using dynamic modeling to extract the Michaelis-Menten constants and the maximal rate for glucose transport and utilization. The ratio of maximal transport rate to cerebral metabolic rate of glucose will be estimated for the hypothalamus by steady-state modeling.
6 secondary outcomes
Antecedent glycemia concentration
Time frame: 14 days
Antecedent physical activity - moderate to vigorous physical activity
Time frame: 14 days
Antecedent physical activity - light physical activity
Time frame: 14 days
Antecedent physical activity - sedentary time
Time frame: 14 days
Antecedent physical activity - energy expenditure
Time frame: 14 days
Antecedent physical activity - sleep quality
Time frame: 14 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2026.
- Individual participant dataSharing planned: No
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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.
Elizabeth R Seaquist, MD principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Experimental hyperglycemia in people with Diabetes Mellitus, Type 1, run by University of Minnesota 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 11 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: under way, not looking for participants, as of the sponsor's last update on 8 Apr 2026. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Glucose kinetics during hyperglycemic clamps before and after induction of IAH (time frame: 240 Minutes). 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 8 Apr 2026.