Ignite Creation Date:
2024-05-06 @ 2:41 AM
Last Modification Date:
2024-10-26 @ 11:22 AM
Study NCT ID:
NCT02104375
Status:
COMPLETED
Last Update Posted:
2015-03-10
First Post:
2014-04-02
Brief Title:
L-citrulline Supplementation Cold Exposure Post-Exercise Muscle Ischemia
Sponsor:
Florida State University
Organization:
Florida State University
Study Overview
Official Title:
The Effects of L-Citrulline Supplementation on Vascular and Cardiac Autonomic Responses to Cold Pressor Test Concurrent With Postexercise Muscle Ischemia
Status:
COMPLETED
Status Verified Date:
2015-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Cardiovascular disease CVD continues to be the major cause of morbidity and mortality in western countries It has been shown that CVD events are known to be higher in the winter than in the summer Low environmental temperatures may induce increased cardiovascular stress resulting in cold-induced hypertension CIH the leading risk factor for CVD events Similar to whole-body cold exposure the cold pressor test CPT an external local cold stimulus has been used for evaluation of cardiovascular and hemodynamic reactivity to sympathetic stimulation It has been shown that brachial blood pressure BP pressure pulse wave reflection aortic BP heart rate HR and arterial stiffness are increased during CPT However the physiologic mechanisms for the cardiovascular complications related to low temperatures are not completely clear
Isometric-handgrip IHG exercise has been used as a tool for assessing cardiovascular autonomic control by a maneuver defined as post-exercise muscle ischemia PEMI PEMI induces exercise pressor reflex metaboreflex by trapping metabolites in the previous active muscle at the cessation of exercise During PEMI the accumulation of contraction-derived metabolites induces sympathetic mediated vascular stimulation and an increased BP whereas the HR fully recovers This suggests that the fall in HR is evoked by an increase in parasympathetic activity which overpowers the sympathetic activation Implication of IHG exercise followed by PEMI provides important clinical information because impaired autonomic and cardiovascular functions are associated with cardiovascular events
Recently oral supplementation with the amino acid L-citrulline L-cit has been proposed as a possible adjunct treatment for hypertension and arterial stiffness L-cit is known to enhance the bioavailability of L-arginine L-arg the endothelial substrate for nitric oxide NO production Cold exposure might include a temperature-dependent inhibition of endothelial NO synthase eNOS the enzyme that produces NO from the amino acid L-arg and may trigger various types of CVD It has been shown that L-cit supplementation has effectively attenuated the CIH response during cold pressor test Thus L-cit supplementation may be effective to reduce the cardiovascular responses associated with cold exposure and the exercise pressor reflex imposed by PEMI Therefore the proposed study is important for the following reasons 1 the results of his study will add to our understanding regarding the cardiovascular and autonomic mechanisms associated with exercise and cold exposure 2 the results of this study will contribute to the development of an adjunct therapy for the prevention of cardiovascular adverse events that are particularly increased during stress such as cold exposure and exercise
Isometric-handgrip IHG exercise has been used as a tool for assessing cardiovascular autonomic control by a maneuver defined as post-exercise muscle ischemia PEMI PEMI induces exercise pressor reflex metaboreflex by trapping metabolites in the previous active muscle at the cessation of exercise During PEMI the accumulation of contraction-derived metabolites induces sympathetic mediated vascular stimulation and an increased BP whereas the HR fully recovers This suggests that the fall in HR is evoked by an increase in parasympathetic activity which overpowers the sympathetic activation Implication of IHG exercise followed by PEMI provides important clinical information because impaired autonomic and cardiovascular functions are associated with cardiovascular events
Recently oral supplementation with the amino acid L-citrulline L-cit has been proposed as a possible adjunct treatment for hypertension and arterial stiffness L-cit is known to enhance the bioavailability of L-arginine L-arg the endothelial substrate for nitric oxide NO production Cold exposure might include a temperature-dependent inhibition of endothelial NO synthase eNOS the enzyme that produces NO from the amino acid L-arg and may trigger various types of CVD It has been shown that L-cit supplementation has effectively attenuated the CIH response during cold pressor test Thus L-cit supplementation may be effective to reduce the cardiovascular responses associated with cold exposure and the exercise pressor reflex imposed by PEMI Therefore the proposed study is important for the following reasons 1 the results of his study will add to our understanding regarding the cardiovascular and autonomic mechanisms associated with exercise and cold exposure 2 the results of this study will contribute to the development of an adjunct therapy for the prevention of cardiovascular adverse events that are particularly increased during stress such as cold exposure and exercise
Detailed Description:
Specific Aims
AIM 1 To determine the acute effects of the exercise pressor response imposed by PEMI with and without CPT on hemodynamics and cardiac autonomic regulation in health overweightobese men
AIM 2 To examine the effects of a 14-day course of L-cit supplementation on arterial stiffness aortic hemodynamics and autonomic regulation at rest and during conditions characterized by increased sympathetic activity IHG PEMI and PEMI concurrent with CPT
Research Hypotheses
Hypothesis 1 There will be greater increases in peripheral and central BP arterial stiffness wave reflection and cardiac sympathetic activity during PEMI concurrent with CPT than during PEMI alone
Hypothesis 2 14 days of L-cit supplementation will attenuate peripheral and central BP wave reflection arterial stiffness and cardiac sympathetic activity responses during IHG exercise PEMI and PEMI concurrent with CPT compared with placebo PL supplementation
Description of the study
A total of twenty male young adults 18-35 years with overweight or obesity body mass index BMI 25 and 40 kgm2 will be enrolled in this study All of the subjects will be nonsmokers no L-cit or L-arg users or regular exercisers defined as more than 120 min per week at least 6 months before the study begins Subjects will be asked to maintain their diet and exercise habits during the study period
Study design
After completion of initial screening cardiovascular and autonomic function of eligible subjects will be evaluated in a quiet temperature-controlled room 22-24C After baseline measurement in a cross-over design fashion subjects will be randomized to either Placebo group Maltodextrin or L-citrulline group for the first 14 days of the study that will be followed by a 14 day washout period and then will be crossed over to their next treatment Cardiovascular function will be evaluated at baseline and after 14 days of the first and the second treatment Measurements will be conducted in the morning after at least 8 hours of an overnight fast in order to avoid potential diurnal variations in BP and vascular reactivity
AIM 1 To determine the acute effects of the exercise pressor response imposed by PEMI with and without CPT on hemodynamics and cardiac autonomic regulation in health overweightobese men
AIM 2 To examine the effects of a 14-day course of L-cit supplementation on arterial stiffness aortic hemodynamics and autonomic regulation at rest and during conditions characterized by increased sympathetic activity IHG PEMI and PEMI concurrent with CPT
Research Hypotheses
Hypothesis 1 There will be greater increases in peripheral and central BP arterial stiffness wave reflection and cardiac sympathetic activity during PEMI concurrent with CPT than during PEMI alone
Hypothesis 2 14 days of L-cit supplementation will attenuate peripheral and central BP wave reflection arterial stiffness and cardiac sympathetic activity responses during IHG exercise PEMI and PEMI concurrent with CPT compared with placebo PL supplementation
Description of the study
A total of twenty male young adults 18-35 years with overweight or obesity body mass index BMI 25 and 40 kgm2 will be enrolled in this study All of the subjects will be nonsmokers no L-cit or L-arg users or regular exercisers defined as more than 120 min per week at least 6 months before the study begins Subjects will be asked to maintain their diet and exercise habits during the study period
Study design
After completion of initial screening cardiovascular and autonomic function of eligible subjects will be evaluated in a quiet temperature-controlled room 22-24C After baseline measurement in a cross-over design fashion subjects will be randomized to either Placebo group Maltodextrin or L-citrulline group for the first 14 days of the study that will be followed by a 14 day washout period and then will be crossed over to their next treatment Cardiovascular function will be evaluated at baseline and after 14 days of the first and the second treatment Measurements will be conducted in the morning after at least 8 hours of an overnight fast in order to avoid potential diurnal variations in BP and vascular reactivity
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None