Clinical trial NCT02866435: Identifying the Brain Substrates of Hypoglycemia Unawareness in Type 1 Diabetes
Official title: Identifying the Brain Substrates of Hypoglycemia Unawareness in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Hypoglycemia
Keywords: MRI
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2016-08-15
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline (i.e., normal glucose levels) functional connectivity, measured as a dimensionless correlation coefficient of MRI signals among brain areas, at hypoglycemia
timeFrame: Baseline and immediately as hypoglycemia starts
measure: Change from baseline (i.e., normal glucose levels) cerebral blood flow, measured in ml/min/100g, at hypoglycemia
timeFrame: Baseline and immediately as hypoglycemia starts
Secondary outcomes:
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Silvia Mangia, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.