Clinical trial NCT04946552: Sympathetic Activation in Obesity
Official title: Sympathetic Activation in Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Healthy
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2021-07-01
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The primary objective of this study is to determine whether sympathetic nervous system (SNS) activity in white adipose tissue (WAT) and brown adipose tissue (BAT), skeletal muscle and brain is altered in individuals with obesity in comparison to individuals with normal weight. Simultaneous multi-organ SNS activation will be obtained with a radiotracer for norepinephrine transporter (NET) for whole-body Positron Emission Tomography (PET) imaging and microneurography (peroneal muscle SNS activity).

The secondary objectives of this study are: 1) to evaluate whether gender differences affect peripheral SNS in healthy normal weight and obese men and women in adipose tissue (WAT and BAT) and muscle (resting/fasting); 2) To investigate the relationship between peripheral and central SNS activity in obesity, by correlating SNS activity in peripheral tissues (WAT, BAT, and muscle) and brain; and 3) To investigate NET CNS and peripheral SNS activity before and after a high carbohydrate mixed meal in lean and obese men and women.


Eligibility criteria: Inclusion Criteria:In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Age 18-45 years
4. In good general health as evidenced by medical history and lean (BMI 18.5-24.9 kg/m2) or non-diabetic obese (BMI 30-50 kg/m2) with a fasting plasma glucose (FPG) \<100 mg/dL and a hemoglobin A1c \<5.7%.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Hypertension
2. Cardiac or pulmonary disease,
3. Known history of Type 1 or Type 2 diabetes
4. Hepatic disease, swallowing and gastrointestinal disorders
5. Current use of anti-obesity medications, supplements and/or anti-hyperglycemic medications
6. Neurological injury or illness, and psychiatric medications
7. Women who are pregnant or lactating
8. Subjects who suffer from claustrophobia
9. Subjects who have received a diagnostic or therapeutic radiopharmaceutical within 7 days prior to participation in this study
10. Radiation works or 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.
11. Subjects with history of IV drug use which would prevent venous access for PET tracer injection
12. Severe motor problems that prevent the subject from lying still for PET and MR imaging
13. Subjects who complain of chronic pain
14. Blood donation within 8 weeks of the study

Primary outcomes:
measure: Distribution Volume Ratio (DVR) of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System
timeFrame: 120 minutes
measure: Microneurography (Muscle Sympathetic Nerve Activity (MSNA)) Measured by Burst Frequency
timeFrame: 30-60 minutes
Secondary outcomes:
measure: DVR of Norepinephrine Transporter (NET) in the Central Nervous System (CNS)
timeFrame: 120 minutes
measure: DVR of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System After Mixed Meal Test
timeFrame: 120 minutes
measure: Plasma Glucose
timeFrame: 2 hours
measure: Insulin Levels
timeFrame: 2 hours
measure: C-Peptide
timeFrame: 2 hours
measure: Plasma Catecholamines (Epinephrine and Norepinephrine)
timeFrame: 2 hours
measure: Plasma Free Fatty Acids (FFA)
timeFrame: 2 hours
measure: Thyroid Function Tests
timeFrame: 2 hours
measure: Electrocardiogram (EKG)- Heart Rate
timeFrame: 30-60 minutes
measure: Electrocardiogram (EKG) - RR Interval
timeFrame: 30-60 minutes
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Church Street Research Unit
state: Connecticut
Study officials:
References: