NCT02056249

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
9

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Jun 2011

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2011

Completed
2.7 years until next milestone

First Submitted

Initial submission to the registry

February 3, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 5, 2014

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2017

Completed
Last Updated

March 6, 2020

Status Verified

March 1, 2020

Enrollment Period

6 years

First QC Date

February 3, 2014

Last Update Submit

March 3, 2020

Conditions

Hypoglycemia

Keywords

hypoglycemiaPositron Emission Tomographynorepinephrine transporter

Outcome Measures

Primary Outcomes (2)

  • norepinephrine transporter (NET) ligand concentrations at Baseline

    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.

    4-8 weeks from initial screening

  • norepinephrine transporter (NET) ligand concentrations in hyperinsulinemic-hypoglycemic Condition

    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).

    4-8 weeks from initial screening

Study Arms (1)

Healthy, lean subjects

Volunteers without anemia (hematocrit), diabetes (A1c), use of illicit drugs and antidepressants, or any other major health issues.

Other: Norepinephrine Transporter (NET) ligand

Interventions

Norepinephrine Transporter (NET) ligandOTHER

Norepinephrine Transporter (NET) ligand for iv administration during Positron Emission Tomography scan to measure changes in brain NET concentration based on insulin levels.

Also known as: [11C]MRB
Healthy, lean subjects

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)
Sampling MethodNon-Probability Sample
Study Population

Potentially eligible subjects (healthy controls) will be recruited through flyers and the Yale web site for this pilot project.

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

PET Center, YCCI Hospital Research Unit (HRU)

New Haven, Connecticut, 06519, United States

Location

Related Publications (1)

  • Belfort-DeAguiar R, Gallezot JD, Hwang JJ, Elshafie A, Yeckel CW, Chan O, Carson RE, Ding YS, Sherwin RS. Noradrenergic Activity in the Human Brain: A Mechanism Supporting the Defense Against Hypoglycemia. J Clin Endocrinol Metab. 2018 Jun 1;103(6):2244-2252. doi: 10.1210/jc.2017-02717.

    PMID: 29590401DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

whole blood

MeSH Terms

Conditions

Hypoglycemia

Interventions

Norepinephrine Plasma Membrane Transport ProteinsLigandsO-methyl reboxetine

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

SymportersIon PumpsMembrane Transport ProteinsCarrier ProteinsProteinsAmino Acids, Peptides, and ProteinsCatecholamine Plasma Membrane Transport ProteinsPlasma Membrane Neurotransmitter Transport ProteinsNeurotransmitter Transport ProteinsSolute Carrier ProteinsMembrane ProteinsLaboratory ChemicalsSpecialty Uses of ChemicalsChemical Actions and Uses

Study Officials

  • Renata Belfort De Aguiar, MD

    Yale University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CROSSOVER
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 3, 2014

First Posted

February 5, 2014

Study Start

June 1, 2011

Primary Completion

June 1, 2017

Study Completion

June 1, 2017

Last Updated

March 6, 2020

Record last verified: 2020-03

Locations

US(1)