The Effects of Supplementing Tyrosine on Blood Pressure in Parkinson's Disease - Full Text View

Purpose

The objective of this experiment is:

Primary: To determine the effects of tyrosine supplementation on orthostatic hypotension in people with PD.
Secondary: To determine the effects of tyrosine supplementation in people with PD with autonomic insufficiency on HR, BP, and norepinephrine responses during acute exercise stress.

Orthostatic hypotension and autonomic abnormalities are a common problem for individuals who suffer from PD, especially as it leads to lightheadedness and falling. For those affected, it can drastically reduce quality of life. It has been hypothesized that tyrosine may impact upon individuals suffering from PD. There is ample evidence in animal models that supports our theory; however there is no clinical evidence of the impact tyrosine supplementation may have in PD patients who suffer from orthostatic hypotension and blunted BP and HR responses. Positive findings that supplemental tyrosine increases BP and HR in people with PD during daily activities such as standing up from a chair and walking can lead to new therapies to improve Parkinsonian orthostatic hypotension.

Hypothesis We will test the hypothesis that symptomatic individuals with PD on dopamine therapy who suffer from orthostatic hypotension and blunted HR and BP responses will improve after tyrosine supplementation.

Condition	Intervention	Phase
Parkinson's Disease	Dietary Supplement: Tyrosine Other: Placebo Comparator:Sugar Pill	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	The Effects of Supplementing Tyrosine on Blood Pressure in Parkinson's Disease

Resource links provided by NLM:

Genetics Home Reference related topics: Parkinson disease Perry syndrome

MedlinePlus related topics: Low Blood Pressure Parkinson's Disease

Drug Information available for: Tyrosine

U.S. FDA Resources

Further study details as provided by New York Institute of Technology:

Primary Outcome Measures:

Determine the effects of tyrosine supplementation on orthostatic hypotension in people with PD [ Time Frame: 7 days ] [ Designated as safety issue: No ]
Orthostatic Blood Pressure Testing:

Subjects will sit and rest for 10 minutes. Blood pressure will be taken in this resting position after the 10 minutes. Subjects will then stand upright for 3 minutes. Blood pressure will be taken every minute for those 3 minutes. A drop in systolic BP of 20 mmHg and a 10 mmHg in diastolic drop within these 3 minutes indicates orthostatic hypotension according to the American Academy of Neurology.

Blood Samples:

Norepinephrine and tyrosine will all be examined via blood samples drawn by a medical assistant or physician from the forearm vein in vacutainer tubes. Two vacutainers of three cc's of blood will be collected and frozen until analyzed.

Secondary Outcome Measures:

To determine the effects of tyrosine supplementation in people with PD with autonomic insufficiency on heart rate, blood pressure, and norepinephrine responses during acute exercise stress. [ Time Frame: 7 days ] [ Designated as safety issue: No ]
An exercise stress test using a Modified Bruce Protocol, which consists of five 3-minute stages on a treadmill, will be used to implement acute stress. During the test, heart rate, oxygen consumption (VO2), Respiratory Exchange Ratio (RER), and 12 lead EKG tracings will be recorded at 1-minute intervals and BP and a rate of perceived exertion (RPE) will be recorded. The treadmill test will conclude when subjects attain peak exercise. Peak exercise will be determined when a subject attains any one of the following: 1) 85% of target heart rate; 2) an RPE of 8; 3) inability to maintain the pace of the treadmill; 4) an RER of over 1.3. Additionally, the American College of Sports Medicine (ACSM) guidelines for terminating exercise testing will be followed.

Subjects will be tested on the first visit and then receive supplementation or placebo for 2x daily for 7 days. Subjects will then repeat all the tests they performed on the first visit.

Estimated Enrollment:	40
Study Start Date:	September 2012
Estimated Study Completion Date:	September 2013
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Tyrosine Tyrosine supplementation (500 mg 2x daily) for 7 days	Dietary Supplement: Tyrosine Tyrosine supplementation (500 mg 2 x daily) for 7 days
Placebo Comparator: Sugar pill Placebo sugar pills (2x daily) for 7 days	Other: Placebo Comparator:Sugar Pill Placebo sugar pills (2x daily

Eligibility

Ages Eligible for Study:	50 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of PD according to the UK Brain Bank Diagnostic criteria
Diagnosis of orthostatic hypotension according to EFNS guidelines
Able to walk on a treadmill comfortably for 6-10 minutes
Currently taking levodopa
Subjects between the age of 50-80 years old

Exclusion Criteria:

Currently taking an amino acid supplement
Currently taking medication that affects BP
Normal BP response to testing

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01676103

Contacts

Contact: Joanne DiFrancisco-Donoghue, PhD

516-686-3759

jdonoghue@nyit.edu

Locations

United States, New York
New York Institue of Technology	Recruiting
Old Westbury, New York, United States, 11568-8000
Contact: Joanne Donoghue, Ph.D. 516-686-3759 jdonoghu@nyit.edu
Principal Investigator: Joanne DiFrancisco-Donoghue, PhD
Sub-Investigator: William G. Werner, PT, EdD
Sub-Investigator: Ely Rabin, PhD
Sub-Investigator: Min-Kyung Jung, PhD

Sponsors and Collaborators

New York Institute of Technology

Michael J. Fox Foundation for Parkinson's Research

Investigators

Principal Investigator:

Joanne DiFrancisco-Donoghue, PhD

New York Institute of Technology

More Information

Publications:

Barbic F, Perego F, Canesi M, Gianni M, Biagiotti S, Costantino G, Pezzoli G, Porta A, Malliani A, Furlan R. Early abnormalities of vascular and cardiac autonomic control in Parkinson's disease without orthostatic hypotension. Hypertension. 2007 Jan;49(1):120-6. Epub 2006 Nov 13.

Kujawa K, Leurgans S, Raman R, Blasucci L, Goetz CG. Acute orthostatic hypotension when starting dopamine agonists in Parkinson's disease. Arch Neurol. 2000 Oct;57(10):1461-3.

Goldstein DS, Holmes CS, Dendi R, Bruce SR, Li ST. Orthostatic hypotension from sympathetic denervation in Parkinson's disease. Neurology. 2002 Apr 23;58(8):1247-55.

Sharabi Y, Goldstein DS. Mechanisms of orthostatic hypotension and supine hypertension in Parkinson disease. J Neurol Sci. 2011 Nov 15;310(1-2):123-8. Epub 2011 Jul 16.

Karobath M, Díaz JL, Huttunen MO. The effect of L-dopa on the concentrations of tryptophan, tyrosine and serotonin in rat brain. Eur J Pharmacol. 1971 May;14(4):393-6.

Growdon JH, Melamed E, Logue M, Hefti F, Wurtman RJ. Effects of oral L-tyrosine administration on CSF tyrosine and homovanillic acid levels in patients with Parkinson's disease. Life Sci. 1982 Mar 8;30(10):827-32.

Glaeser BS, Melamed E, Growdon JH, Wurtman RJ. Elevation of plasma tyrosine after a single oral dose of L-tyrosine. Life Sci. 1979 Jul 16;25(3):265-71.

Stryjer R, Klein C, Treves TA, Rabey JM. The effects of acute loading with levodopa and levodopa with selegiline on blood pressure and plasma norepinephrine levels in chronic Parkinson's disease patients. Acta Neurol Scand. 2005 Feb;111(2):89-94.

Tipre DN, Goldstein DS. Cardiac and extracardiac sympathetic denervation in Parkinson's disease with orthostatic hypotension and in pure autonomic failure. J Nucl Med. 2005 Nov;46(11):1775-81.

Riederer P. L-dopa competes with tyrosine and tryptophan for human brain uptake. Nutr Metab. 1980;24(6):417-23.

Deijen JB, Orlebeke JF. Effect of tyrosine on cognitive function and blood pressure under stress. Brain Res Bull. 1994;33(3):319-23.

Conlay LA, Maher TJ, Wurtman RJ. Tyrosine increases blood pressure in hypotensive rats. Science. 1981 May 1;212(4494):559-60.

Conlay LA, Maher TJ, Wurtman RJ. Tyrosine accelerates catecholamine synthesis in hemorrhaged hypotensive rats. Brain Res. 1985 Apr 29;333(1):81-4.

Lahrmann H, Cortelli P, Hilz M, Mathias CJ, Struhal W, Tassinari M. EFNS guidelines on the diagnosis and management of orthostatic hypotension. Eur J Neurol. 2006 Sep;13(9):930-6.

DiFrancisco-Donoghue J, Elokda A, Lamberg EM, Bono N, Werner WG. Norepinephrine and cardiovascular responses to maximal exercise in Parkinson's disease on and off medication. Mov Disord. 2009 Sep 15;24(12):1773-8.

Responsible Party:	New York Institute of Technology
ClinicalTrials.gov Identifier:	NCT01676103 History of Changes
Other Study ID Numbers:	BHS-797
Study First Received:	August 28, 2012
Last Updated:	April 28, 2013
Health Authority:	United States: Institutional Review Board United States: Food and Drug Administration

Keywords provided by New York Institute of Technology:

Parkinson's Disease (PD)
Orthostatic hypotension (OH)

Additional relevant MeSH terms:

Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases

Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases

ClinicalTrials.gov processed this record on June 18, 2013