Sympathetic Activation in Obesity

Yale University

Status: Completed

Conditions: Healthy; Obesity

Treatments: Diagnostic Test: PET Scan; Diagnostic Test: CT Scan; Other: Body Composition, Percent Body Fat & Percent Body Water (Tanita scale); Diagnostic Test: Oral Glucose Tolerance Test; Diagnostic Test: Muscle sympathetic nerve activity (MSNA); Dietary Supplement: Mixed Meal Test; Other: Body Composition, Percent Body Fat & Percent Body Water (DXA Scan)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04946552

1R56DK129344-01 (U.S. NIH Grant/Contract)

2000030749

Details and patient eligibility

About

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.

Enrollment: 5 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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5 participants in 2 patient groups

Individuals with normal BMI

Active Comparator group

Description:

(BMI 18-25 kg/m2)

Treatment:

Other: Body Composition, Percent Body Fat & Percent Body Water (Tanita scale)

Diagnostic Test: Muscle sympathetic nerve activity (MSNA)

Diagnostic Test: Oral Glucose Tolerance Test

Diagnostic Test: PET Scan

Diagnostic Test: CT Scan

Other: Body Composition, Percent Body Fat & Percent Body Water (DXA Scan)

Dietary Supplement: Mixed Meal Test

Individuals with obesity

Active Comparator group

Description:

(BMI 30-40 kg/m2)

Treatment:

Other: Body Composition, Percent Body Fat & Percent Body Water (Tanita scale)

Diagnostic Test: Muscle sympathetic nerve activity (MSNA)

Diagnostic Test: Oral Glucose Tolerance Test

Diagnostic Test: PET Scan

Diagnostic Test: CT Scan

Other: Body Composition, Percent Body Fat & Percent Body Water (DXA Scan)

Dietary Supplement: Mixed Meal Test