<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/NCT03000127</url>
  </required_header>
  <id_info>
    <org_study_id>1R01NS102295</org_study_id>
    <nct_id>NCT03000127</nct_id>
  </id_info>
  <brief_title>Testosterone for Fatigue in Men With MS</brief_title>
  <official_title>A Pilot Trial of Testosterone Treatment for Fatigue in Men With Multiple Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, Los Angeles</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Fatigue is a major symptom in people with multiple sclerosis (MS), for which treatments are&#xD;
      limited. Several studies have shown that a large proportion of men with MS have low&#xD;
      testosterone levels. We propose a two-site clinical trial using topical testosterone gel as a&#xD;
      treatment for MS-related fatigue in men with progressive MS who have low or low-normal&#xD;
      testosterone levels.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Lack of funding&#xD;
  </why_stopped>
  <start_date type="Anticipated">July 1, 2018</start_date>
  <completion_date type="Anticipated">January 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Single arm, testosterone or placebo will be administered to all patients at some period of study, but which period of study the they will recieve placebo or testosterone gel will be blinded (unknown) to participant, care provider, and outcomes assessor.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>All patients will receive either testosterone or placebo at some phase of treatment, but which phase will be testosterone and which will be placebo will be unknown (blinded) to participant, care provider, and outcomes assessor.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Modified Fatigue Impact Scale (MFIS)</measure>
    <time_frame>18 months</time_frame>
    <description>assessment of fatigue severity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Localized Gray Matter Atrophy</measure>
    <time_frame>18 months</time_frame>
    <description>Quantify effect of testosterone treatment on localized gray matter atrophy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Axon Density in White Matter</measure>
    <time_frame>18 months</time_frame>
    <description>Quantify effect of testosterone treatment on axon density in major white matter tracts</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Correlation of testosterone level with fatigue</measure>
    <time_frame>18 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Correlation of localized gray matter atrophy with fatigue</measure>
    <time_frame>18 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Correlation of axon density in white matter with fatigue</measure>
    <time_frame>18 months</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Single arm crossover</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients will receive testosterone gel and placebo gel during some months, but the months that they are on each treatment will be unknown to the patient</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AndroGel 1 % Topical Gel</intervention_name>
    <description>testosterone gel</description>
    <arm_group_label>Single arm crossover</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>Placebo gel</description>
    <arm_group_label>Single arm crossover</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1) Men with SPMS or PPMS, 2)18-60 years old, 3) EDSS of 1.0- 6.5, 4) Low or low-normal T &lt;&#xD;
        499ng/dL and 5) FSS scores of &gt;3.6.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1) Prostate specific antigen &gt; 2.5 (&lt;49yr of age) or &gt;3.5 (age &gt;50yr of age), 2) baseline&#xD;
        hematocrit greater than the upper limit of normal for the laboratory used, 3) EKG with&#xD;
        ischemic changes, 4) history of myocardial infarction, unstable angina, stroke, transient&#xD;
        ischemic attack, or deep vein thrombosis, 5) history of prostate or breast cancer, 6)&#xD;
        screening T level &gt;500ng/dL, 7) diabetes requiring treatment, 8) current drug/alcohol&#xD;
        abuse, 9) disease other than MS causing fatigue, such as obstructive sleep apnea or other&#xD;
        sleep disorder, or untreated thyroid dysfunction, 10) RRMS, 11) Beck Depression&#xD;
        Inventory-II (BDI) score over 20, 12) cognitive dysfunction such that subject cannot&#xD;
        perform study tests, 13) inability to undergo MRI, 14) current or expected use of&#xD;
        amphetamines, or 15) anticipated changes in medical treatments that might affect fatigue&#xD;
        scores (e.g., expected changes in spasticity, sleep, or depression medications).&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of California, Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Sicotte NL, Giesser BS, Tandon V, Klutch R, Steiner B, Drain AE, Shattuck DW, Hull L, Wang HJ, Elashoff RM, Swerdloff RS, Voskuhl RR. Testosterone treatment in multiple sclerosis: a pilot study. Arch Neurol. 2007 May;64(5):683-8. doi: 10.1001/archneur.64.5.683.</citation>
    <PMID>17502467</PMID>
  </reference>
  <reference>
    <citation>Kurth F, Luders E, Sicotte NL, Gaser C, Giesser BS, Swerdloff RS, Montag MJ, Voskuhl RR, Mackenzie-Graham A. Neuroprotective effects of testosterone treatment in men with multiple sclerosis. Neuroimage Clin. 2014 Mar 6;4:454-60. doi: 10.1016/j.nicl.2014.03.001. eCollection 2014.</citation>
    <PMID>24634831</PMID>
  </reference>
  <reference>
    <citation>Gold SM, Chalifoux S, Giesser BS, Voskuhl RR. Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone. J Neuroinflammation. 2008 Jul 31;5:32. doi: 10.1186/1742-2094-5-32.</citation>
    <PMID>18671877</PMID>
  </reference>
  <reference>
    <citation>Ziehn MO, Avedisian AA, Dervin SM, Umeda EA, O'Dell TJ, Voskuhl RR. Therapeutic testosterone administration preserves excitatory synaptic transmission in the hippocampus during autoimmune demyelinating disease. J Neurosci. 2012 Sep 5;32(36):12312-24. doi: 10.1523/JNEUROSCI.2796-12.2012.</citation>
    <PMID>22956822</PMID>
  </reference>
  <reference>
    <citation>Gold SM, Voskuhl RR. Estrogen and testosterone therapies in multiple sclerosis. Prog Brain Res. 2009;175:239-51. doi: 10.1016/S0079-6123(09)17516-7.</citation>
    <PMID>19660660</PMID>
  </reference>
  <reference>
    <citation>Liva SM, Voskuhl RR. Testosterone acts directly on CD4+ T lymphocytes to increase IL-10 production. J Immunol. 2001 Aug 15;167(4):2060-7. doi: 10.4049/jimmunol.167.4.2060.</citation>
    <PMID>11489988</PMID>
  </reference>
  <reference>
    <citation>Dalal M, Kim S, Voskuhl RR. Testosterone therapy ameliorates experimental autoimmune encephalomyelitis and induces a T helper 2 bias in the autoantigen-specific T lymphocyte response. J Immunol. 1997 Jul 1;159(1):3-6.</citation>
    <PMID>9200430</PMID>
  </reference>
  <reference>
    <citation>Golden LC, Voskuhl R. The importance of studying sex differences in disease: The example of multiple sclerosis. J Neurosci Res. 2017 Jan 2;95(1-2):633-643. doi: 10.1002/jnr.23955.</citation>
    <PMID>27870415</PMID>
  </reference>
  <reference>
    <citation>Spence RD, Voskuhl RR. Neuroprotective effects of estrogens and androgens in CNS inflammation and neurodegeneration. Front Neuroendocrinol. 2012 Jan;33(1):105-15. doi: 10.1016/j.yfrne.2011.12.001. Epub 2011 Dec 24.</citation>
    <PMID>22209870</PMID>
  </reference>
  <reference>
    <citation>Hussain R, Ghoumari AM, Bielecki B, Steibel J, Boehm N, Liere P, Macklin WB, Kumar N, Habert R, Mhaouty-Kodja S, Tronche F, Sitruk-Ware R, Schumacher M, Ghandour MS. The neural androgen receptor: a therapeutic target for myelin repair in chronic demyelination. Brain. 2013 Jan;136(Pt 1):132-46. doi: 10.1093/brain/aws284.</citation>
    <PMID>23365095</PMID>
  </reference>
  <reference>
    <citation>Voskuhl RR, Gold SM. Sex-related factors in multiple sclerosis susceptibility and progression. Nat Rev Neurol. 2012 Mar 27;8(5):255-63. doi: 10.1038/nrneurol.2012.43.</citation>
    <PMID>22450508</PMID>
  </reference>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>December 17, 2016</study_first_submitted>
  <study_first_submitted_qc>December 17, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>November 4, 2019</last_update_submitted>
  <last_update_submitted_qc>November 4, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, Los Angeles</investigator_affiliation>
    <investigator_full_name>Rhonda Voskuhl</investigator_full_name>
    <investigator_title>Professor, Department of Neurology</investigator_title>
  </responsible_party>
  <keyword>testosterone</keyword>
  <keyword>multiple sclerosis</keyword>
  <keyword>fatigue</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
    <mesh_term>Fatigue</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Testosterone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03000127
org study id: 1R01NS102295
nct id: NCT03000127
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Fatigue is a major symptom in people with multiple sclerosis (MS), for which treatments are
      limited. Several studies have shown that a large proportion of men with MS have low
      testosterone levels. We propose a two-site clinical trial using topical testosterone gel as a
      treatment for MS-related fatigue in men with progressive MS who have low or low-normal
      testosterone levels.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single arm, testosterone or placebo will be administered to all patients at some period of study, but which period of study the they will recieve placebo or testosterone gel will be blinded (unknown) to participant, care provider, and outcomes assessor.
primary purpose: Treatment
masking: None (Open Label)
masking description: All patients will receive either testosterone or placebo at some phase of treatment, but which phase will be testosterone and which will be placebo will be unknown (blinded) to participant, care provider, and outcomes assessor.
measure: Modified Fatigue Impact Scale (MFIS)
time frame: 18 months
description: assessment of fatigue severity
measure: Localized Gray Matter Atrophy
time frame: 18 months
description: Quantify effect of testosterone treatment on localized gray matter atrophy
measure: Axon Density in White Matter
time frame: 18 months
description: Quantify effect of testosterone treatment on axon density in major white matter tracts
measure: Correlation of testosterone level with fatigue
time frame: 18 months
measure: Correlation of localized gray matter atrophy with fatigue
time frame: 18 months
measure: Correlation of axon density in white matter with fatigue
time frame: 18 months
arm group label: Single arm crossover
arm group type: Experimental
description: All patients will receive testosterone gel and placebo gel during some months, but the months that they are on each treatment will be unknown to the patient
intervention type: Drug
intervention name: AndroGel 1 % Topical Gel
description: testosterone gel
arm group label: Single arm crossover
intervention type: Drug
intervention name: Placebos
description: Placebo gel
arm group label: Single arm crossover
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
facility: 
facility: 
country: United States
citation: Sicotte NL, Giesser BS, Tandon V, Klutch R, Steiner B, Drain AE, Shattuck DW, Hull L, Wang HJ, Elashoff RM, Swerdloff RS, Voskuhl RR. Testosterone treatment in multiple sclerosis: a pilot study. Arch Neurol. 2007 May;64(5):683-8. doi: 10.1001/archneur.64.5.683.
PMID: 17502467
citation: Kurth F, Luders E, Sicotte NL, Gaser C, Giesser BS, Swerdloff RS, Montag MJ, Voskuhl RR, Mackenzie-Graham A. Neuroprotective effects of testosterone treatment in men with multiple sclerosis. Neuroimage Clin. 2014 Mar 6;4:454-60. doi: 10.1016/j.nicl.2014.03.001. eCollection 2014.
PMID: 24634831
citation: Gold SM, Chalifoux S, Giesser BS, Voskuhl RR. Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone. J Neuroinflammation. 2008 Jul 31;5:32. doi: 10.1186/1742-2094-5-32.
PMID: 18671877
citation: Ziehn MO, Avedisian AA, Dervin SM, Umeda EA, O'Dell TJ, Voskuhl RR. Therapeutic testosterone administration preserves excitatory synaptic transmission in the hippocampus during autoimmune demyelinating disease. J Neurosci. 2012 Sep 5;32(36):12312-24. doi: 10.1523/JNEUROSCI.2796-12.2012.
PMID: 22956822
citation: Gold SM, Voskuhl RR. Estrogen and testosterone therapies in multiple sclerosis. Prog Brain Res. 2009;175:239-51. doi: 10.1016/S0079-6123(09)17516-7.
PMID: 19660660
citation: Liva SM, Voskuhl RR. Testosterone acts directly on CD4+ T lymphocytes to increase IL-10 production. J Immunol. 2001 Aug 15;167(4):2060-7. doi: 10.4049/jimmunol.167.4.2060.
PMID: 11489988
citation: Dalal M, Kim S, Voskuhl RR. Testosterone therapy ameliorates experimental autoimmune encephalomyelitis and induces a T helper 2 bias in the autoantigen-specific T lymphocyte response. J Immunol. 1997 Jul 1;159(1):3-6.
PMID: 9200430
citation: Golden LC, Voskuhl R. The importance of studying sex differences in disease: The example of multiple sclerosis. J Neurosci Res. 2017 Jan 2;95(1-2):633-643. doi: 10.1002/jnr.23955.
PMID: 27870415
citation: Spence RD, Voskuhl RR. Neuroprotective effects of estrogens and androgens in CNS inflammation and neurodegeneration. Front Neuroendocrinol. 2012 Jan;33(1):105-15. doi: 10.1016/j.yfrne.2011.12.001. Epub 2011 Dec 24.
PMID: 22209870
citation: Hussain R, Ghoumari AM, Bielecki B, Steibel J, Boehm N, Liere P, Macklin WB, Kumar N, Habert R, Mhaouty-Kodja S, Tronche F, Sitruk-Ware R, Schumacher M, Ghandour MS. The neural androgen receptor: a therapeutic target for myelin repair in chronic demyelination. Brain. 2013 Jan;136(Pt 1):132-46. doi: 10.1093/brain/aws284.
PMID: 23365095
citation: Voskuhl RR, Gold SM. Sex-related factors in multiple sclerosis susceptibility and progression. Nat Rev Neurol. 2012 Mar 27;8(5):255-63. doi: 10.1038/nrneurol.2012.43.
PMID: 22450508
responsible party type: Principal Investigator
investigator affiliation: University of California, Los Angeles
investigator full name: Rhonda Voskuhl
investigator title: Professor, Department of Neurology
mesh term: Multiple Sclerosis
mesh term: Sclerosis
mesh term: Fatigue
mesh term: Testosterone
sharing ipd: No