Evaluation of the Effect of Hypoglycemia With PET and a Norepinephrine Transporter Ligand
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ClinicalTrials.gov Identifier: NCT02056249 |
Recruitment Status :
Completed
First Posted : February 5, 2014
Last Update Posted : March 6, 2020
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The aim of this study is to use Positron Emission Tomography (PET) imaging to measure changes in norepinephrine transporter (NET) concentrations in the brain and periphery of healthy individuals during hypoglycemia.
We hypothesize that during hypoglycemia, NE levels will increase within the brain, especially the hypothalamus, and this likely contributes to activation of glucose counterregulatory responses. We further hypothesize that during hypoglycemia, NET concentrations in key glucoregulatory regions will change in order to sustain or prolong sympathetic nervous system activation of counterregulatory responses.
Condition or disease | Intervention/treatment |
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Hypoglycemia | Other: Norepinephrine Transporter (NET) ligand |

Study Type : | Observational |
Actual Enrollment : | 9 participants |
Observational Model: | Case-Crossover |
Time Perspective: | Prospective |
Official Title: | Evaluation of the Effect of Hypoglycemia on the Noradrenergic System With PET and a Highly Selective Norepinephrine Transporter Ligand |
Study Start Date : | June 2011 |
Actual Primary Completion Date : | June 2017 |
Actual Study Completion Date : | June 2017 |

Group/Cohort | Intervention/treatment |
---|---|
Healthy, lean subjects
Volunteers without anemia (hematocrit), diabetes (A1c), use of illicit drugs and antidepressants, or any other major health issues.
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Other: Norepinephrine Transporter (NET) ligand
Norepinephrine Transporter (NET) ligand for iv administration during Positron Emission Tomography scan to measure changes in brain NET concentration based on insulin levels.
Other Name: [11C]MRB |
- norepinephrine transporter (NET) ligand concentrations at Baseline [ Time Frame: 4-8 weeks from initial screening ]An IV catheter may be inserted in the other hand to allow drawing of continuous blood for measurement of tracer kinetics. PET scans will be done as subjects rest, the tracer will be injected, and initial data will be acquired on the scanner.
- norepinephrine transporter (NET) ligand concentrations in hyperinsulinemic-hypoglycemic Condition [ Time Frame: 4-8 weeks from initial screening ]Once baseline study has been completed, a continuous intravenous infusion of insulin (2mU/kg/min) will be started along with a variable infusion of 20% glucose to lower and maintain plasma glucose levels ~55 mg/dL for 30 min before the second injection of [the tracer and PET scanning. The hyperinsulinemic-hypoglycemic glucose clamp will continue throughout the 2nd PET study (90-120 min for brain and ~30 min for periphery).
Biospecimen Retention: Samples With DNA

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Ages Eligible for Study: | 18 Years to 55 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Sampling Method: | Non-Probability Sample |
Inclusion Criteria:
- Males or females between 18 and 55 years of age
- Who are able to give voluntary written informed consent
- Able to tolerate PET and MR imaging
- Have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator.
- Have no current uncontrolled medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology
- Have no history of a neurological or psychiatric disorder
- No history of previous allergic reactions to drugs
- Do not suffer from claustrophobia or any MRI contradictions
Exclusion Criteria:
- History of liver disease
- Pregnancy/breast feeding (as documented by pregnancy testing at screening and on days of the imaging studies).
- Anemia (Hct <37 in women and < 40 in men)
- Presence of acute or unstable medical or neurological illness. Subjects will be excluded from the study if they present with any history of serious medical or neurological illness or if they show signs of a major medical or neurological illness on examination or lab testing including history of seizures, head injury, brain tumor, heart, liver or kidney disease, eating disorder, diabetes.
- Drug abuse (except nicotine)(Nicotine dependence will be permitted in all groups but controlled for in the analysis).
- Use of antidepressants.
- Clotting disorders or recent anticoagulant therapy.
- MRI-incompatible implants and other contraindications for MRI, such as pace-maker, artificial joints, non-removable body piercings, tattoos larger than 1 cm in diameter, claustrophobia, etc
- Clinically significant pulmonary, renal, cardiac or hepatic impairment or cancer, have clinically significant infectious disease, including AIDS or HIV infection, or previous positive test for hepatitis B, hepatitis C, HIV-1, or HIV-2; subjects will be asked about this. No testing will be performed.
- Have received a diagnostic or therapeutic radiopharmaceutical within 7 days prior to participation in this study.
- Blood donation during the 8-week period preceding the PET scan.
- Participation in other research studies involving ionizing radiation within one year of the PET scans that would cause the subject to exceed the yearly dose limits for normal volunteers.
- Unable to fast overnight prior to the PET scan.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02056249
United States, Connecticut | |
PET Center, YCCI Hospital Research Unit (HRU) | |
New Haven, Connecticut, United States, 06519 |
Principal Investigator: | Renata Belfort De Aguiar, MD | Yale University |
Responsible Party: | Yale University |
ClinicalTrials.gov Identifier: | NCT02056249 |
Other Study ID Numbers: |
1103008163 5R01DK020495 ( U.S. NIH Grant/Contract ) |
First Posted: | February 5, 2014 Key Record Dates |
Last Update Posted: | March 6, 2020 |
Last Verified: | March 2020 |
hypoglycemia Positron Emission Tomography norepinephrine transporter |
Hypoglycemia Glucose Metabolism Disorders Metabolic Diseases Norepinephrine Adrenergic alpha-Agonists Adrenergic Agonists Adrenergic Agents |
Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Sympathomimetics Autonomic Agents Peripheral Nervous System Agents Vasoconstrictor Agents |