- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02866435
Identifying the Brain Substrates of Hypoglycemia Unawareness in Type 1 Diabetes
January 29, 2021 updated by: University of Minnesota
The purpose of this study is to investigate how the brain responds to low blood glucose in non-diabetic individuals.
The ultimate goal is to understand the brain substrates of hypoglycemia unawareness, a condition that can occur in patients with type1 diabetes undergoing insulin treatment.In the present study, the investigators focus on differences between two groups of non-diabetic subjects: one group who experienced two episodes of hypoglycemia the day prior to the study (and supposedly developed some level of unawareness to hypoglycemia), and one group who did not.
In this study, a 3 tesla MRI scanner is used to acquire brain images.
The imaging system is identical to the ones used in hospitals.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Hypoglycemia, also called low blood glucose or low blood sugar, occurs when blood glucose drops below normal levels.
When blood glucose starts to drop, the body reacts to this drop, trying to restore the blood glucose level.
Symptoms of hypoglycemia are usually easily recognized.
Hypoglycemia can be treated quickly and easily by eating or drinking a small amount of glucose-rich food.
However some people with long history of diabetes can have an impaired response to hypoglycemia and therefore don't recognize the symptoms of hypoglycemia, condition called hypoglycemia unawareness.
If not treated hypoglycemia can get worse and cause confusion, clumsiness, fainting etc.
Currently, it is not fully understood which brain areas are involved in sensing the drop of glucose levels.
Absence of such knowledge is a critical barrier to the design and monitoring of effective intervention strategies to avoid and/or reverse hypoglycemia unawareness.
The purpose of this study is to investigate how the brain responds to low blood glucose in non-diabetic individuals.
Specific focus is given to differences between two groups of non-diabetic subjects: one group who experienced two episodes of hypoglycemia the day prior to the study (and therefore supposedly developed some level of unawareness to hypoglycemia), and one group who did not.
Study Type
Interventional
Enrollment (Actual)
27
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
-
-
Minnesota
-
Minneapolis, Minnesota, United States, 55455
- University of Minnesota
-
-
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
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
Participants will be included in the study, if they
- are non-diabetic
- are evaluated as not contraindicated (based on exclusion criteria)
- are age (within 5 years), gender, and body mass index (within 4 kg/m2) matched to patients with type 1 diabetes who have participated to a similar study which involved only the second part (day 2) of the current protocol.
Exclusion Criteria:
Participants will be excluded from the study, if they
- have any type of bio-implant activated by mechanical, electronic, or magnetic means (e.g. cochlear implants, pacemakers, neurostimulators, bio stimulators, electronic infusion pumps)
- have any type of ferromagnetic bio-implant that could potentially be displaced or damaged, such as aneurysm clips, metallic skull plates, etc
- have any retained metal in their body, either from a medical procedure or an injury
- have history of stroke, seizures, neurosurgical procedures, or arrhythmias
- are pregnant
- are currently using medication that can alter glucose metabolism or brain perfusion
- weight more than 300lbs (limit for MRI scanner)
- have concomitant medical problems that may prevent them from successfully completing the protocol
- lack capacity to consent
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: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Euglycemia pre-conditioning
Participants will undergo two euglycemia (normal blood sugar) clamps (8-10 am and 1-3 pm) on day 1, where the target glucose during the clamp will be 95 mg/dl.
For each clamp, participants will be given intravenous insulin for two hours and blood glucose will be maintained at target by the infusion of 20% dextrose, the rate of which will be adjusted based on measured blood glucose values collected every 5 minutes.
Potassium phosphate will also be infused during each clamp.
On next day (day 2), participants will undergo MRI session during experimental hypoglycemia, i.e., while their blood sugar is clamped from normal value to low value.
|
In each clamp, a small intravenous catheter is placed in participant's arm for infusion of insulin together with potassium phosphate and glucose.
Insulin is a hormone that body makes naturally and it causes blood sugar to decrease.
Insulin (and glucose) will be infused in calculated doses to maintain blood sugar level in the target range of 95 mg/dl or 50 mg/dl depending on the clamp.
Other Names:
Glucose is administered together with insulin and potassium phosphate during each clamp via the intravenous catheter.
Glucose is a sugar and it is used to carefully regulate blood sugar level.
Other Names:
Potassium phosphate is administered together with glucose and insulin during each clamp via the intravenous catheter.
Potassium is a salt-like substance that is present in the blood.
Other Names:
|
Experimental: Hypoglycemia pre-conditioning
Participants will undergo two hypoglycemia (low blood sugar) clamps (8-10 am and 1-3 pm) on day 1, where target glucose during the clamp will be 50 mg/dl.
For each clamp, participants will be given intravenous insulin for two hours and blood glucose will be maintained at target by the infusion of 20% dextrose, the rate of which will be adjusted based on measured blood glucose values collected every 5 minutes.
Potassium phosphate will also be infused during each clamp.
On next day (day 2), participants will undergo MRI session during experimental hypoglycemia, i.e., while their blood sugar is clamped from normal value to low value.
|
In each clamp, a small intravenous catheter is placed in participant's arm for infusion of insulin together with potassium phosphate and glucose.
Insulin is a hormone that body makes naturally and it causes blood sugar to decrease.
Insulin (and glucose) will be infused in calculated doses to maintain blood sugar level in the target range of 95 mg/dl or 50 mg/dl depending on the clamp.
Other Names:
Glucose is administered together with insulin and potassium phosphate during each clamp via the intravenous catheter.
Glucose is a sugar and it is used to carefully regulate blood sugar level.
Other Names:
Potassium phosphate is administered together with glucose and insulin during each clamp via the intravenous catheter.
Potassium is a salt-like substance that is present in the blood.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change from baseline (i.e., normal glucose levels) functional connectivity, measured as a dimensionless correlation coefficient of MRI signals among brain areas, at hypoglycemia
Time Frame: Baseline and immediately as hypoglycemia starts
|
Functional connectivity will be measured with MRI at 3 Tesla
|
Baseline and immediately as hypoglycemia starts
|
Change from baseline (i.e., normal glucose levels) cerebral blood flow, measured in ml/min/100g, at hypoglycemia
Time Frame: Baseline and immediately as hypoglycemia starts
|
Cerebral blood flow will be measured with MRI at 3 Tesla
|
Baseline and immediately as hypoglycemia starts
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Silvia Mangia, PhD, University of Minnesota
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Mangia S, Tesfaye N, De Martino F, Kumar AF, Kollasch P, Moheet AA, Eberly LE, Seaquist ER. Hypoglycemia-induced increases in thalamic cerebral blood flow are blunted in subjects with type 1 diabetes and hypoglycemia unawareness. J Cereb Blood Flow Metab. 2012 Nov;32(11):2084-90. doi: 10.1038/jcbfm.2012.117. Epub 2012 Aug 15.
- Bolo NR, Musen G, Simonson DC, Nickerson LD, Flores VL, Siracusa T, Hager B, Lyoo IK, Renshaw PF, Jacobson AM. Functional Connectivity of Insula, Basal Ganglia, and Prefrontal Executive Control Networks during Hypoglycemia in Type 1 Diabetes. J Neurosci. 2015 Aug 5;35(31):11012-23. doi: 10.1523/JNEUROSCI.0319-15.2015.
- Wiegers EC, Becker KM, Rooijackers HM, von Samson-Himmelstjerna FC, Tack CJ, Heerschap A, de Galan BE, van der Graaf M. Cerebral blood flow response to hypoglycemia is altered in patients with type 1 diabetes and impaired awareness of hypoglycemia. J Cereb Blood Flow Metab. 2017 Jun;37(6):1994-2001. doi: 10.1177/0271678X16658914. Epub 2016 Jan 1.
- Rooijackers HM, Wiegers EC, Tack CJ, van der Graaf M, de Galan BE. Brain glucose metabolism during hypoglycemia in type 1 diabetes: insights from functional and metabolic neuroimaging studies. Cell Mol Life Sci. 2016 Feb;73(4):705-22. doi: 10.1007/s00018-015-2079-8. Epub 2015 Oct 31.
Helpful Links
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 1, 2016
Primary Completion (Actual)
September 30, 2019
Study Completion (Actual)
December 30, 2019
Study Registration Dates
First Submitted
August 5, 2016
First Submitted That Met QC Criteria
August 10, 2016
First Posted (Estimate)
August 15, 2016
Study Record Updates
Last Update Posted (Actual)
February 1, 2021
Last Update Submitted That Met QC Criteria
January 29, 2021
Last Verified
January 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1608M92941
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
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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