Clinical trial NCT00341770: Assessment of Sympathetic Nervous System Activity by Microneurography Recording Technique
Official title: Assessment of Sympathetic Nervous System Activity by Microneurography Recording Technique
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Nervous System
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2006-06-21
Enrollment: 600
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no

Brief summary: Obesity is the consequence of an imbalance between energy intake and energy expenditure. Recent studies have suggested that the sympathetic nervous system (SNS) may be an important determinant of the rate of energy expenditure in man. Indirect assessments of the sympathetic nervous activity in Pima Indians have recently shown impaired SNS-mediated energy expenditure in this obesity-prone population. We plan to perform direct microelectrode nerve recording of the sympathetic innervation of the lower leg to directly assess SNS activity and examine its potential role in the regulation of metabolic rate and the development of obesity. Measurements will be performed in the basal state, in response to glucose feeding (75 g OGTT) and in response to glucose/insulin infusion. These studies also will help to disassociate the effect of insulin and glucose on the stimulation of SNS activity. Energy expenditure measurements will be performed over 24 hours in the respiratory chamber and for 2 1/2 hours before and during the euglycemic clamp. Results also will be used to determine possible racial differences between Pimas and Caucasians, since the risk for obesity is markedly different in these populations. To exclude the possibility of a "normal" SNS activity but with peripheral resistance to the action of norepineprine, we will perform adrenergic stimulation by isoproterenol to measure peripheral adrenergic sensitivity.

Detailed description: Obesity is the consequence of an imbalance between energy intake and energy expenditure. Recent studies have suggested that the sympathetic nervous system (SNS) may be an important determinant of the rate of energy expenditure in man. Indirect assessments of the sympathetic nervous activity in Pima Indians have recently shown impaired SNS-mediated energy expenditure in this obesity-prone population. We plan to perform direct microelectrode nerve recording of the sympathetic innervation of the lower leg to directly assess SNS activity and examine its potential role in the regulation of metabolic rate and the development of obesity. Measurements will be performed in the basal state, in response to glucose feeding (75 g OGTT), in response to a standard meal, and in response to glucose/insulin infusion. These studies also will help to disassociate the effect of insulin and glucose on the stimulation of SNS activity. The association between postprandial changes in SNS activity and subjective ratings of hunger and fullness also will be studied. Energy expenditure measurements will be performed over 24 hours in the respiratory chamber and for 2 1/2 hours before and during the euglycemic clamp. Results also will be used to determine possible racial differences between Pimas and Caucasians, since the risk for obesity is markedly different in these populations. To exclude the possibility of a "normal" SNS activity but with peripheral resistance to the action of norepineprine, we will perform adrenergic stimulation by isoproterenol to measure peripheral adrenergic sensitivity.

Eligibility criteria: * INCLUSION CRITERIA:

Male and female Pima Indians, age 4 years old and older.

Male and female Caucasians, age 4 years old and older.

Offspring of Diabetic and Non-Diabetic mothers will be recruited.

Male and female monozygotic and dizygotic twins of any racial background between the ages of 4-7 will be considered for study.

Indian subjects will be recruited from the Gila River Indian Community.

Only children found in good health on the basis of the medical history and physical examination will be accepted into the study.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: NIDDK, Phoenix
state: Arizona
Study officials:
References:
citation: Bray GA, York DA, Fisler JS. Experimental obesity: a homeostatic failure due to defective nutrient stimulation of the sympathetic nervous system. Vitam Horm. 1989;45:1-125. doi: 10.1016/s0083-6729(08)60393-3.
citation: Ravussin E, Lillioja S, Knowler WC, Christin L, Freymond D, Abbott WG, Boyce V, Howard BV, Bogardus C. Reduced rate of energy expenditure as a risk factor for body-weight gain. N Engl J Med. 1988 Feb 25;318(8):467-72. doi: 10.1056/NEJM198802253180802.
citation: O'Dea K, Esler M, Leonard P, Stockigt JR, Nestel P. Noradrenaline turnover during under- and over-eating in normal weight subjects. Metabolism. 1982 Sep;31(9):896-9. doi: 10.1016/0026-0495(82)90178-0.