Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT06256276 |
Other study ID # |
202617 |
Secondary ID |
|
Status |
Completed |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
July 26, 2016 |
Est. completion date |
February 1, 2018 |
Study information
Verified date |
January 2024 |
Source |
University of Arkansas |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Recent studies suggest that patients with heart failure (HF) may have a reduced ability to
control the tone of their blood vessels, heart rate or blood pressure in response to stress.
This study will test whether 16 weeks of protein supplements can improve control of blood
pressure and heart rate in HF patients.
Description:
Heart Failure is defined as "a complex clinical syndrome that can result from any structural
or functional cardiac disorder that impairs the ability of the ventricle to fill or eject
blood." The New York Heart Association classifies heart failure four functional classes: NYHA
1-4, with Class 1 as minimal and Class 4 as the most advanced stage.
As a clinical syndrome, HF can be associated with significant limitations in functional
capacity which can be very debilitating in the elderly population. It is a major cause of
morbidity and mortality and is the leading cause of hospitalization among older individuals
in the United States (1-15), particularly among those aged ≥65 years (16, 18). Nearly 1
million hospitalizations for HF occur each year with rates of hospitalization continuing to
rise. Prevalence of heart failure was estimated to be more than 5.8 million in the United
States and HF was singled out as an emerging epidemic (17).
Heart failure is associated with autonomic and endothelial dysfunction. Recent studies
suggest that patients with HF maybe more prone to having impaired vasomotor and autonomic
response to stress (19-29). A reduced ability to increase blood flow or heart rate
appropriately in response to demand could limit the functional capacity of these subjects and
would contribute to orthostasis (drop in blood pressure on standing). Another factor
contributing to orthostasis in these individuals is poor muscle tone in the lower extremities
reducing venous flow.
Endothelial dysfunction in HF on the other hand is attributed to decreased production of NO
and increased oxidative stress due to neurohumoral activation, release of inflammatory
messengers from the myocardium, altered local shear force and resultant atherogenesis (30,
31). The endothelial dysfunction itself causes an increase in the production of cytokines,
uncoupling of eNOS and further increases the oxidative stress (32-35). The endothelium helps
in regulating the vascular tone by balancing the production of vasodilators and
vasoconstrictors in response to various stimuli (36) and its dysfunction would also impair
baroreceptor function which in turn would affect cardiac autonomic activity and blood flow.
In our research we hope to improve both autonomic and endothelial function by supplementing
protein and carnitine in diet. Studies have shown that when protein is metabolized to the
amino acids L-arginine and citrulline, there is increased synthesis of NO (37). L-arginine, a
semi-essential basic amino acid, is a precursor in the formation of nitric oxide by the
enzyme nitric oxide synthase and directly increases the formation of NO (38). The
administration of arginine and/or citrulline in patients in HF has been reported to improve
endothelial function. Systolic and diastolic arterial pressures as well as pulmonary arterial
systolic pressure have been shown to decrease significantly after administration of arginine
or citrulline administration, which in turn improves right ventricular diastolic diameter
(37, 39). One clinical study reported improvement in pulmonary artery pressure and right
ventricular ejection fraction after two months of oral supplementation with L-arginine or
citrulline in patients with HF and right ventricular dysfunction (39). It is hoped that
protein supplementation will improve autonomic function by having a positive impact on
physiological and biochemical parameters, including nitric oxide synthesis which is expect
will improve baroreceptor blood flow, autonomic BP and HR in response to tilt.
Carnitine supplementation of 1g/d for 12 wk in hemodialysis patients significantly reduced
systemic inflammation, as reflected by decreases in CRP, IL-1β, and IL-6 (40). In obesity,
the mitochondrial abnormalities of reduced fatty acid oxidation, incomplete β-oxidation, and
impaired substrate switching from fatty acid to pyruvate were reversed after 8wks of oral
supplementation with the same dosage of carnitine (41). It is anticipated the same beneficial
effects of carnitine in individuals with HF.
The purpose of this study is to evaluate the effects of 16 weeks of protein supplementation
on measures of autonomic regulation of blood pressure and heart rate, as well as physical
strength and function in elderly subjects with mild to moderate heart failure (NYHA 1, 2, or
3). Each participant will be randomized to one of two groups (whey protein + L-carnitine or
placebos). Study endpoints will be measured at baseline and after 4 months of treatment.