<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/NCT02230930</url>
  </required_header>
  <id_info>
    <org_study_id>46934</org_study_id>
    <nct_id>NCT02230930</nct_id>
  </id_info>
  <brief_title>Treatment of Apomorphine-induced Skin Reactions: a Pilot Study</brief_title>
  <official_title>Open-label Crossover Trial to Investigate the Efficacy of Treatments in Apomorphine-induced Skin Reactions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medical Center Groningen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Medical Center Groningen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Skin reactions as a result of continuous subcutaneous apomorphine infusion occur frequently&#xD;
      and interfere with the absorption of apomorphine. The histopathology of apomorphine-induced&#xD;
      skin reactions is poorly understood. Therefore treatment options are limited and suggestive.&#xD;
&#xD;
      Objective: to investigate the efficacy of four treatments including massage, dilution of&#xD;
      apomorphine, treatment with topical hydrocortisone and pre-treatment with subcutaneous&#xD;
      administered hydrocortisone, in Parkinson's disease patients with apomorphine-induced skin&#xD;
      reactions.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>June 2015</start_date>
  <completion_date type="Anticipated">November 2017</completion_date>
  <primary_completion_date type="Anticipated">October 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes on global perceived effect scale</measure>
    <time_frame>14 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in histological skin tissue characteristics</measure>
    <time_frame>14 days</time_frame>
    <description>Histological skin tissue characteristics are presence of eosinophils, melanin-like pigment, fibrosis, lymphocytes and histiocytes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in nodule size (diameter)</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in erythema size (diameter)</measure>
    <time_frame>14 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Eosinophilia</measure>
    <time_frame>14 days</time_frame>
    <description>Defined as increased absolute eosinophil count</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Personal or family history of atopic constellation</measure>
    <time_frame>14 days</time_frame>
    <description>Assessed with a questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Personal or family history of allergies</measure>
    <time_frame>14 days</time_frame>
    <description>Assessed with a questionnaire</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Liver enzymes</measure>
    <time_frame>14 days</time_frame>
    <description>aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (AF), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gGT)</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Parkinson's Disease</condition>
  <condition>Apomorphine-induced Skin Reactions</condition>
  <arm_group>
    <arm_group_label>Massage with a spiky ball</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects are instructed to massage the apomorphine-induced skin reactions with a spiky ball 3 times a day for 2 minutes for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hydrocortisone cream 1%</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects are instructed to apply hydrocortisone cream 1% once daily for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Subcutaneous hydrocortisone 10mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects are instructed to administer subcutaneous hydrocortisone (Solu-Cortef 10mg) prior to apomorphine via the subcutaneous infusion line which is used for administration of apomorphine, for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Apomorphine 0.25% (2.5mg/ml)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects are instructed to dilute apomorphine 0.5% (5mg/ml) with the same volume of physiologic saline (NaCl 0.9%) to 0.25% (2.5mg/ml). Apomorphine will be infused subcutaneously for 14 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apomorphine 0.25% (2.5mg/ml)</intervention_name>
    <description>Apomorphine 0.5% (5mg/ml) will be diluted to 0.25% (2.5mg/ml) by the addition of the same volume physiological saline (NaCl 0.9%).</description>
    <arm_group_label>Apomorphine 0.25% (2.5mg/ml)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Massage with a spiky ball</intervention_name>
    <description>Each patient will massage skin reactions with a spiky ball 3 times a day for 2 minutes.</description>
    <arm_group_label>Massage with a spiky ball</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydrocortisone cream 1%</intervention_name>
    <description>Hydrocortisone cream 1% (1mg/g) will be administered on each nodule one time a day</description>
    <arm_group_label>Hydrocortisone cream 1%</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Subcutaneous hydrocortisone 10mg</intervention_name>
    <description>Subcutaneous hydrocortisone 10mg will be administered previous to apomorphine infusion making use of the apomorphine infusion system</description>
    <arm_group_label>Subcutaneous hydrocortisone 10mg</arm_group_label>
    <other_name>Solu-Cortef</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female and male subjects aged ≥30;&#xD;
&#xD;
          -  Diagnosis of idiopathic Parkinson's disease of &gt;3 years' duration, defined by the&#xD;
             United Kingdom (UK) Brain Bank criteria, with the exception of &gt;1 affected relative&#xD;
             being allowed, without any other known or suspected cause of Parkinsonism (Gibb &amp;&#xD;
             Lees, 1988);&#xD;
&#xD;
          -  Treatment with continuous subcutaneous apomorphine infusion;&#xD;
&#xD;
          -  Having apomorphine-induced skin reactions (i.e. erythema, swelling and/or nodule&#xD;
             formation);&#xD;
&#xD;
          -  Male and female patients must be compliant with a highly effective contraceptive&#xD;
             method (oral hormonal contraception alone is not considered highly effective and must&#xD;
             be used in combination with a barrier method) during the study, if sexually active;&#xD;
&#xD;
          -  Subjects considered reliable and capable of adhering to the protocol, visit schedule,&#xD;
             and medication intake according to the judgement of the investigator.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  High suspicion of other parkinsonian syndromes;&#xD;
&#xD;
          -  History of respiratory depression;&#xD;
&#xD;
          -  Hypersensitivity to hydrocortisone or any excipients of the medicinal product;&#xD;
&#xD;
          -  Concomitant therapy with histamine antagonist;&#xD;
&#xD;
          -  Known with Cushing's disease or hypercortisolism&#xD;
&#xD;
          -  Any medical condition that is likely to interfere with an adequate participation in&#xD;
             the study including e.g. current diagnosis of unstable epilepsy; clinically relevant&#xD;
             cardiac dysfunction and/or myocardial infarction or stroke within the last 12 months;&#xD;
&#xD;
          -  Pregnant and breastfeeding women;&#xD;
&#xD;
          -  Current infectious disease with fever at the time of investigation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Teus Van Laar, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Medical Center Groningen</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Robbert WK Borgemeester, MD</last_name>
    <phone>+31 (0) 50-3611519</phone>
    <email>r.w.k.borgemeester@umcg.nl</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Neurology</name>
      <address>
        <city>Groningen</city>
        <zip>9713GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Robbert Borgemeester, MD</last_name>
      <phone>+31 (0) 50-3611519</phone>
      <email>r.w.k.borgemeester@umcg.nl</email>
    </contact>
    <investigator>
      <last_name>Robbert Borgemeester, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Teus van Laar, MD PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>August 29, 2014</study_first_submitted>
  <study_first_submitted_qc>August 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2014</study_first_posted>
  <last_update_submitted>May 1, 2017</last_update_submitted>
  <last_update_submitted_qc>May 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 2, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Medical Center Groningen</investigator_affiliation>
    <investigator_full_name>Teus van Laar</investigator_full_name>
    <investigator_title>MD PhD</investigator_title>
  </responsible_party>
  <keyword>Parkinson's disease</keyword>
  <keyword>Apomorphine</keyword>
  <keyword>Infusion</keyword>
  <keyword>Skin reactions</keyword>
  <keyword>Subcutaneous nodules</keyword>
  <keyword>Hydrocortisone</keyword>
  <keyword>Massage</keyword>
  <keyword>Dilution</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydrocortisone</mesh_term>
    <mesh_term>Hydrocortisone 17-butyrate 21-propionate</mesh_term>
    <mesh_term>Hydrocortisone acetate</mesh_term>
    <mesh_term>Hydrocortisone hemisuccinate</mesh_term>
    <mesh_term>Apomorphine</mesh_term>
  </intervention_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/NCT02230930
org study id: 46934
nct id: NCT02230930
lead sponsor: 
has dmc: No
Skin reactions as a result of continuous subcutaneous apomorphine infusion occur frequently
      and interfere with the absorption of apomorphine. The histopathology of apomorphine-induced
      skin reactions is poorly understood. Therefore treatment options are limited and suggestive.

      Objective: to investigate the efficacy of four treatments including massage, dilution of
      apomorphine, treatment with topical hydrocortisone and pre-treatment with subcutaneous
      administered hydrocortisone, in Parkinson's disease patients with apomorphine-induced skin
      reactions.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Changes on global perceived effect scale
time frame: 14 days
measure: Changes in histological skin tissue characteristics
time frame: 14 days
description: Histological skin tissue characteristics are presence of eosinophils, melanin-like pigment, fibrosis, lymphocytes and histiocytes.
measure: Changes in nodule size (diameter)
time frame: 14 days
measure: Changes in erythema size (diameter)
time frame: 14 days
measure: Eosinophilia
time frame: 14 days
description: Defined as increased absolute eosinophil count
measure: Personal or family history of atopic constellation
time frame: 14 days
description: Assessed with a questionnaire
measure: Personal or family history of allergies
time frame: 14 days
description: Assessed with a questionnaire
measure: Liver enzymes
time frame: 14 days
description: aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (AF), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gGT)
arm group label: Massage with a spiky ball
arm group type: Active Comparator
description: Subjects are instructed to massage the apomorphine-induced skin reactions with a spiky ball 3 times a day for 2 minutes for 14 days.
arm group label: Hydrocortisone cream 1%
arm group type: Active Comparator
description: Subjects are instructed to apply hydrocortisone cream 1% once daily for 14 days.
arm group label: Subcutaneous hydrocortisone 10mg
arm group type: Active Comparator
description: Subjects are instructed to administer subcutaneous hydrocortisone (Solu-Cortef 10mg) prior to apomorphine via the subcutaneous infusion line which is used for administration of apomorphine, for 14 days.
arm group label: Apomorphine 0.25% (2.5mg/ml)
arm group type: Active Comparator
description: Subjects are instructed to dilute apomorphine 0.5% (5mg/ml) with the same volume of physiologic saline (NaCl 0.9%) to 0.25% (2.5mg/ml). Apomorphine will be infused subcutaneously for 14 days.
intervention type: Drug
intervention name: Apomorphine 0.25% (2.5mg/ml)
description: Apomorphine 0.5% (5mg/ml) will be diluted to 0.25% (2.5mg/ml) by the addition of the same volume physiological saline (NaCl 0.9%).
arm group label: Apomorphine 0.25% (2.5mg/ml)
intervention type: Device
intervention name: Massage with a spiky ball
description: Each patient will massage skin reactions with a spiky ball 3 times a day for 2 minutes.
arm group label: Massage with a spiky ball
intervention type: Drug
intervention name: Hydrocortisone cream 1%
description: Hydrocortisone cream 1% (1mg/g) will be administered on each nodule one time a day
arm group label: Hydrocortisone cream 1%
intervention type: Drug
intervention name: Subcutaneous hydrocortisone 10mg
description: Subcutaneous hydrocortisone 10mg will be administered previous to apomorphine infusion making use of the apomorphine infusion system
arm group label: Subcutaneous hydrocortisone 10mg
other name: Solu-Cortef
criteria: 
gender: All
minimum age: 30 Years
maximum age: N/A
healthy volunteers: No
last name: Teus Van Laar, MD PhD
role: Principal Investigator
affiliation: University Medical Center Groningen
last name: Robbert WK Borgemeester, MD
phone: +31 (0) 50-3611519
email: r.w.k.borgemeester@umcg.nl
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: University Medical Center Groningen
investigator full name: Teus van Laar
investigator title: MD PhD
mesh term: Parkinson Disease
mesh term: Hydrocortisone
mesh term: Hydrocortisone 17-butyrate 21-propionate
mesh term: Hydrocortisone acetate
mesh term: Hydrocortisone hemisuccinate
mesh term: Apomorphine