Trial Outcomes & Findings for Sympathetic Activation in Obesity (NCT NCT04946552)

Results Overview

Lean individuals with a BMI of 18-25 and obese individuals with a BMI of 30-40 will undergo a PET/CT scan to determine group differences in sympathetic nervous system (SNS) activity in white adipose tissue (WAT), brown adipose tissue (BAT), and deltoid muscle. SNS activity will be determined by using \[11C\]MRB a radiotracer for PET imaging.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

5 participants

Primary outcome timeframe

120 minutes

Results posted on

2024-02-16

Participant Flow

Participant milestones

Participant milestones
Measure	Individuals With Normal BMI BMI 18-25 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan	Individuals With Obesity BMI 30-40 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan
Overall Study STARTED	3	2
Overall Study COMPLETED	3	2
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sympathetic Activation in Obesity

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall n=5 Participants Presented are baseline characteristics overall as there were only 2 people in a single treatment arm and therefore identifying information could be obtained.
Age, Continuous	32.4 years STANDARD_DEVIATION 1.2 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	2 Participants n=5 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants
Weight	68.45 kilograms STANDARD_DEVIATION 4.2 • n=5 Participants
Body Mass Index (BMI)	30.65 kg/m2 STANDARD_DEVIATION 2.5 • n=5 Participants
Systolic Blood Pressure (BP)	108.85 mmHg STANDARD_DEVIATION 8.55 • n=5 Participants
Diastolic BP	67.85 mmHg STANDARD_DEVIATION 6.6 • n=5 Participants
Insulin Sensitivity Index (ISI) Score using the Matsuda Index	2.95 score on a scale STANDARD_DEVIATION 0.65 • n=5 Participants
Study Group Obese Group (BMI Greater than 25 kg/m2)	2 Participants n=5 Participants
Study Group Lean Group (BMI 18-25 kg/m2)	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 120 minutes

Lean individuals with a BMI of 18-25 and obese individuals with a BMI of 30-40 will undergo a PET/CT scan to determine group differences in sympathetic nervous system (SNS) activity in white adipose tissue (WAT), brown adipose tissue (BAT), and deltoid muscle. SNS activity will be determined by using \[11C\]MRB a radiotracer for PET imaging.

Outcome measures

Outcome measures
Measure	Individuals With Normal BMI n=3 Participants BMI 18-25 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan	Individuals With Obesity n=2 Participants BMI 30-40 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan
Distribution Volume Ratio (DVR) of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System Brain: Caudate	0.095 DVR Standard Deviation 0.063	-0.03 DVR Standard Deviation 0.028
Distribution Volume Ratio (DVR) of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System Brain: Thalamus	0.295 DVR Standard Deviation 0.205	-0.115 DVR Standard Deviation 0.092
Distribution Volume Ratio (DVR) of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System Brain: Raphe	-0.255 DVR Standard Deviation 0.049	-0.455 DVR Standard Deviation 0.657
Distribution Volume Ratio (DVR) of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System Muscle: Deltoid	0.525 DVR Standard Deviation 0.058	0.549 DVR Standard Deviation 0.107
Distribution Volume Ratio (DVR) of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System Brain: Putamen	0.13 DVR Standard Deviation 0.014	-0.025 DVR Standard Deviation 0.120
Distribution Volume Ratio (DVR) of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System Brain: Hypothalamus	-0.095 DVR Standard Deviation 0.691	-0.195 DVR Standard Deviation 0.332
Distribution Volume Ratio (DVR) of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System Brain: Locus Ceruleus	-1.47 DVR Standard Deviation 1.49	-0.01 DVR Standard Deviation 0.283
Distribution Volume Ratio (DVR) of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System Brain: Paracentral Lobule	0.045 DVR Standard Deviation 0.587	-0.055 DVR Standard Deviation 0.191

PRIMARY outcome

Timeframe: 30-60 minutes

Muscle sympathetic nerve activity will be quantified by identification and measurement of sympathetic bursts in the integrated neurogram and expressed as burst frequency (mean number of bursts per unit time) to determinate group differences in peroneal MSNA at baseline (fasting) and during MMT.

Outcome measures

Outcome measures
Measure	Individuals With Normal BMI n=3 Participants BMI 18-25 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan	Individuals With Obesity n=2 Participants BMI 30-40 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan
Microneurography (Muscle Sympathetic Nerve Activity (MSNA)) Measured by Burst Frequency Fasting	11.18 bursts per minute Standard Deviation 1.58	9.541 bursts per minute Standard Deviation 0.245
Microneurography (Muscle Sympathetic Nerve Activity (MSNA)) Measured by Burst Frequency MMT	15.63 bursts per minute Standard Deviation 4.8	11.60 bursts per minute Standard Deviation 2.61

SECONDARY outcome

Timeframe: 120 minutes

Regional quantification of \[11C\]MRB uptake as distribution volume ratio (DVR ) will be used to measure NET in the CNS.

Outcome measures

Outcome measures
Measure	Individuals With Normal BMI n=3 Participants BMI 18-25 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan	Individuals With Obesity n=2 Participants BMI 30-40 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan
DVR of Norepinephrine Transporter (NET) in the Central Nervous System (CNS)	0.549 DVR Standard Deviation 0.107	0.525 DVR Standard Deviation 0.058

SECONDARY outcome

Timeframe: 120 minutes

Measurement of peripheral SNS Activity with \[11C\]MRC for PET/CT before (fasting) and after a high carbohydrate mixed meal in individuals with normal weight and obesity.

Outcome measures

Outcome measures
Measure	Individuals With Normal BMI n=3 Participants BMI 18-25 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan	Individuals With Obesity n=2 Participants BMI 30-40 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan
DVR of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System After Mixed Meal Test Fasting	0.577 DVR Standard Deviation 0.121	0.491 DVR Standard Deviation 0.041
DVR of [11C]MRB PET Imaging of Peripheral Sympathetic Nervous System After Mixed Meal Test MMT	0.521 DVR Standard Deviation 0.128	0.559 DVR Standard Deviation 0.061

SECONDARY outcome

Timeframe: 2 hours

Population: Data for this outcome was not collected

Measurement of plasma glucose levels will be obtained at fasting and during the Mixed Meal Test (MMT). The normal range for glucose levels is 70-100 mg/dL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 hours

Measurement of plasma insulin levels will be obtained at fasting and during the MMT. Insulin levels in the plasma are higher in individuals with obesity. The normal range for insulin is: \< or = 19.6 mcg/dL

Outcome measures

Outcome measures
Measure	Individuals With Normal BMI n=3 Participants BMI 18-25 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan	Individuals With Obesity n=2 Participants BMI 30-40 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan
Insulin Levels Fasting	7.07 uU/mL Standard Deviation 0.568	15.55 uU/mL Standard Deviation 0.327
Insulin Levels MMT	61.06 uU/mL Standard Deviation 54.3	78.37 uU/mL Standard Deviation 45.96

SECONDARY outcome

Timeframe: 2 hours

Population: Data for this outcome was not collected

Plasma samples will be drawn at baseline and throughout the MMT for measurement of C-Peptide. The normal range for C-Peptide is 0.80 - 3.85 ng/mL

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 hours

Measurement of epinephrine and norepinephrine levels in the plasma at fasting and during the MMT. The normal range for epinephrine is 0 to 140 pg/mL (764.3 pmol/L). The normal range for norepinephrine is 70 to 1700 pg/mL (413.8 to 10048.7 pmol/L).

Outcome measures

Outcome measures
Measure	Individuals With Normal BMI n=3 Participants BMI 18-25 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan	Individuals With Obesity n=2 Participants BMI 30-40 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan
Plasma Catecholamines (Epinephrine and Norepinephrine) Epinephrine Fasting	0.0487 mg/mL Standard Deviation 0.0167	0.0131 mg/mL Standard Deviation 0.0238
Plasma Catecholamines (Epinephrine and Norepinephrine) Epinephrine MMT	0.0155 mg/mL Standard Deviation 0	0.0136 mg/mL Standard Deviation 0.0138
Plasma Catecholamines (Epinephrine and Norepinephrine) Norepinephrine Fasting	0.146 mg/mL Standard Deviation 0.0376	0.135 mg/mL Standard Deviation 0.0572
Plasma Catecholamines (Epinephrine and Norepinephrine) Norepinephrine MMT	0.278 mg/mL Standard Deviation 0.109	0.162 mg/mL Standard Deviation 0.0779

SECONDARY outcome

Timeframe: 2 hours

Percent of plasma free fatty acids levels will be obtained at fasting and during the Mixed Meal Test (MMT). FFA levels in the plasma are higher in individuals with obesity than individuals with normal weight.

Outcome measures

Outcome measures
Measure	Individuals With Normal BMI n=3 Participants BMI 18-25 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan	Individuals With Obesity n=2 Participants BMI 30-40 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan
Plasma Free Fatty Acids (FFA) Fasting	380 percentage of FFA Standard Deviation 42.91	412 percentage of FFA Standard Deviation 37.702
Plasma Free Fatty Acids (FFA) MMT	419 percentage of FFA Standard Deviation 19.20	404 percentage of FFA Standard Deviation 35.40

SECONDARY outcome

Timeframe: 2 hours

Population: Data for this outcome was not collected

Plasma samples will be drawn at baseline and throughout the mixed meal test (MMT) for measurement of Thyroid Stimulating Hormone (TSH), free T4 (FT4) and total T3 (TT3). The normal range for TSH is : 0.4-4.5 mlU/L, FT4: 0.8-1.8 ng/dL, TT3: 76 - 181 ng/dL.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 30-60 minutes

EKG surface electrodes will be applied to the chest for measurement of heart rate and heart rate variability (QT Interval).

Outcome measures

Outcome measures
Measure	Individuals With Normal BMI n=3 Participants BMI 18-25 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan	Individuals With Obesity n=2 Participants BMI 30-40 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan
Electrocardiogram (EKG)- Heart Rate Fasting	61.8 beats per minute Standard Deviation 6.47	74.2 beats per minute Standard Deviation 4.06
Electrocardiogram (EKG)- Heart Rate MMT	65.6 beats per minute Standard Deviation 9.97	71.7 beats per minute Standard Deviation 5.32

SECONDARY outcome

Timeframe: 30-60 minutes

EKG surface electrodes will be applied to the chest for measurement of RR interval.

Outcome measures

Outcome measures
Measure	Individuals With Normal BMI n=3 Participants BMI 18-25 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan	Individuals With Obesity n=2 Participants BMI 30-40 kg/m2 PET Scan, Mixed Meal Test, Muscle sympathetic nerve activity (MSNA), Oral Glucose Tolerance Test, Body Composition, Percent Body Fat \& Percent Body Water, CT Scan
Electrocardiogram (EKG) - RR Interval MMT	0.91 seconds Standard Deviation 0.07	0.85 seconds Standard Deviation 0.16
Electrocardiogram (EKG) - RR Interval Fasting	0.94 seconds Standard Deviation 0.16	1.01 seconds Standard Deviation 0.11

Adverse Events

Individuals With Normal BMI

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Individuals With Obesity

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Renata Belfort De Aguiar, MD, PhD

Yale School of Medicine

Phone: (203) 785-5331

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place