<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01676103</url>
  </required_header>
  <id_info>
    <org_study_id>BHS-797</org_study_id>
    <nct_id>NCT01676103</nct_id>
  </id_info>
  <brief_title>The Effects of Supplementing Tyrosine on Blood Pressure in Parkinson's Disease</brief_title>
  <official_title>The Effects of Supplementing Tyrosine on Blood Pressure in Parkinson's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>New York Institute of Technology</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Michael J. Fox Foundation for Parkinson's Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>New York Institute of Technology</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this experiment is:&#xD;
&#xD;
        -  Primary: To determine the effects of tyrosine supplementation on orthostatic hypotension&#xD;
           in people with PD.&#xD;
&#xD;
        -  Secondary: To determine the effects of tyrosine supplementation in people with PD with&#xD;
           autonomic insufficiency on HR, BP, and norepinephrine responses during acute exercise&#xD;
           stress.&#xD;
&#xD;
      Orthostatic hypotension and autonomic abnormalities are a common problem for individuals who&#xD;
      suffer from PD, especially as it leads to lightheadedness and falling. For those affected, it&#xD;
      can drastically reduce quality of life. It has been hypothesized that tyrosine may impact&#xD;
      upon individuals suffering from PD. There is ample evidence in animal models that supports&#xD;
      our theory; however there is no clinical evidence of the impact tyrosine supplementation may&#xD;
      have in PD patients who suffer from orthostatic hypotension and blunted BP and HR responses.&#xD;
      Positive findings that supplemental tyrosine increases BP and HR in people with PD during&#xD;
      daily activities such as standing up from a chair and walking can lead to new therapies to&#xD;
      improve Parkinsonian orthostatic hypotension.&#xD;
&#xD;
      Hypothesis We will test the hypothesis that symptomatic individuals with PD on dopamine&#xD;
      therapy who suffer from orthostatic hypotension and blunted HR and BP responses will improve&#xD;
      after tyrosine supplementation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">November 2013</completion_date>
  <primary_completion_date type="Actual">November 2013</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Determine the effects of tyrosine supplementation on orthostatic hypotension in people with PD</measure>
    <time_frame>7 days</time_frame>
    <description>Orthostatic Blood Pressure Testing:&#xD;
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.&#xD;
Blood Samples:&#xD;
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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>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.</measure>
    <time_frame>7 days</time_frame>
    <description>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.&#xD;
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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Parkinson's Disease</condition>
  <arm_group>
    <arm_group_label>Tyrosine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tyrosine supplementation (500 mg 2x daily) for 7 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sugar pill</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo sugar pills (2x daily) for 7 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Tyrosine</intervention_name>
    <description>Tyrosine supplementation (500 mg 2 x daily) for 7 days</description>
    <arm_group_label>Tyrosine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo Comparator:Sugar Pill</intervention_name>
    <description>Placebo sugar pills (2x daily</description>
    <arm_group_label>Sugar pill</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of PD according to the UK Brain Bank Diagnostic criteria&#xD;
&#xD;
          -  Diagnosis of orthostatic hypotension according to EFNS guidelines&#xD;
&#xD;
          -  Able to walk on a treadmill comfortably for 6-10 minutes&#xD;
&#xD;
          -  Currently taking levodopa&#xD;
&#xD;
          -  Subjects between the age of 50-80 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Currently taking an amino acid supplement&#xD;
&#xD;
          -  Currently taking medication that affects BP&#xD;
&#xD;
          -  Normal BP response to testing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joanne DiFrancisco-Donoghue, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>New York Institute of Technology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>New York Institue of Technology</name>
      <address>
        <city>Old Westbury</city>
        <state>New York</state>
        <zip>11568-8000</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>17101845</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>11030798</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>11971094</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>21762927</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>5157767</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>6175872</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>481129</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>15644067</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>16269589</PMID>
  </reference>
  <reference>
    <citation>Riederer P. L-dopa competes with tyrosine and tryptophan for human brain uptake. Nutr Metab. 1980;24(6):417-23. doi: 10.1159/000176359.</citation>
    <PMID>7219901</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>8293316</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>7209553</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>3995291</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>16930356</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>19562762</PMID>
  </reference>
  <verification_date>April 2014</verification_date>
  <study_first_submitted>August 28, 2012</study_first_submitted>
  <study_first_submitted_qc>August 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 30, 2012</study_first_posted>
  <last_update_submitted>April 15, 2014</last_update_submitted>
  <last_update_submitted_qc>April 15, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 16, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Parkinson's Disease (PD)</keyword>
  <keyword>Orthostatic hypotension (OH)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01676103
org study id: BHS-797
nct id: NCT01676103
lead sponsor: 
collaborator: 
has dmc: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Determine the effects of tyrosine supplementation on orthostatic hypotension in people with PD
time frame: 7 days
description: 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.
measure: 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
description: 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.
arm group label: Tyrosine
arm group type: Experimental
description: Tyrosine supplementation (500 mg 2x daily) for 7 days
arm group label: Sugar pill
arm group type: Placebo Comparator
description: Placebo sugar pills (2x daily) for 7 days
intervention type: Dietary Supplement
intervention name: Tyrosine
description: Tyrosine supplementation (500 mg 2 x daily) for 7 days
arm group label: Tyrosine
intervention type: Other
intervention name: Placebo Comparator:Sugar Pill
description: Placebo sugar pills (2x daily
arm group label: Sugar pill
criteria: 
gender: All
minimum age: 50 Years
maximum age: 80 Years
healthy volunteers: No
last name: Joanne DiFrancisco-Donoghue, PhD
role: Principal Investigator
affiliation: New York Institute of Technology
facility: 
country: United States
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
responsible party type: Sponsor
mesh term: Parkinson Disease