The Effects of Supplementing Tyrosine on Blood Pressure in Parkinson's Disease

NCT01676103 | Completed Phase 1

• 1 other identifier: BHS-797
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson's Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Determine the effects of tyrosine supplementation on orthostatic hypotension in people with PD

  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.

  7 days

Secondary Outcomes (1)

• 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.

  7 days

Study Arms (2)

Tyrosine

EXPERIMENTAL

Tyrosine supplementation (500 mg 2x daily) for 7 days

Dietary Supplement: Tyrosine

Sugar pill

PLACEBO COMPARATOR

Placebo sugar pills (2x daily) for 7 days

Other: Placebo Comparator:Sugar Pill

Interventions

Tyrosine DIETARY_SUPPLEMENT

Tyrosine supplementation (500 mg 2 x daily) for 7 days

Tyrosine

Placebo Comparator:Sugar Pill OTHER

Placebo sugar pills (2x daily

Sugar pill

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• New York Institute of Technology: lead
• Michael J. Fox Foundation for Parkinson's Research: collaborator

Study Sites (1)

New York Institue of Technology

Old Westbury, New York, 11568-8000, United States

Location

Related Publications (16)

• 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. doi: 10.1161/01.HYP.0000250939.71343.7c. Epub 2006 Nov 13.

  PMID: 17101845 BACKGROUND

• 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. doi: 10.1001/archneur.57.10.1461.

  PMID: 11030798 BACKGROUND

• 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. doi: 10.1212/wnl.58.8.1247.

  PMID: 11971094 BACKGROUND

• 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. doi: 10.1016/j.jns.2011.06.047. Epub 2011 Jul 16.

  PMID: 21762927 BACKGROUND

• Karobath M, Diaz 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. doi: 10.1016/0014-2999(71)90195-6. No abstract available.

  PMID: 5157767 BACKGROUND

• 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. doi: 10.1016/0024-3205(82)90596-3.

  PMID: 6175872 BACKGROUND

• 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. doi: 10.1016/0024-3205(79)90294-7. No abstract available.

  PMID: 481129 BACKGROUND

• 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. doi: 10.1111/j.1600-0404.2005.00294.x.

  PMID: 15644067 BACKGROUND

• 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.

  PMID: 16269589 BACKGROUND

• Riederer P. L-dopa competes with tyrosine and tryptophan for human brain uptake. Nutr Metab. 1980;24(6):417-23. doi: 10.1159/000176359.

  PMID: 7219901 BACKGROUND

• Deijen JB, Orlebeke JF. Effect of tyrosine on cognitive function and blood pressure under stress. Brain Res Bull. 1994;33(3):319-23. doi: 10.1016/0361-9230(94)90200-3.

  PMID: 8293316 BACKGROUND

• Conlay LA, Maher TJ, Wurtman RJ. Tyrosine increases blood pressure in hypotensive rats. Science. 1981 May 1;212(4494):559-60. doi: 10.1126/science.7209553.

  PMID: 7209553 BACKGROUND

• Conlay LA, Maher TJ, Wurtman RJ. Tyrosine accelerates catecholamine synthesis in hemorrhaged hypotensive rats. Brain Res. 1985 Apr 29;333(1):81-4. doi: 10.1016/0006-8993(85)90126-x.

  PMID: 3995291 BACKGROUND

• 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. doi: 10.1111/j.1468-1331.2006.01512.x.

  PMID: 16930356 BACKGROUND

• 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. doi: 10.1002/mds.22612.

  PMID: 19562762 BACKGROUND

• DiFrancisco-Donoghue J, Rabin E, Lamberg EM, Werner WG. Effects of Tyrosine on Parkinson's Disease: A Randomized, Double-Blind, Placebo-Controlled Trial. Mov Disord Clin Pract. 2014 Oct 23;1(4):348-353. doi: 10.1002/mdc3.12082. eCollection 2014 Dec.

  PMID: 30363894 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Hypotension, Orthostatic

Interventions

Tyrosine

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Joanne DiFrancisco-Donoghue, PhD

  New York Institute of Technology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2012
• First Posted: August 30, 2012
• Study Start: September 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: April 16, 2014

Record last verified: 2014-04

Locations

US (1)