<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/NCT02192931</url>
  </required_header>
  <id_info>
    <org_study_id>73034</org_study_id>
    <nct_id>NCT02192931</nct_id>
  </id_info>
  <brief_title>A Randomized Double-Blind Controlled Trial of Creatine in Female Methamphetamine Users</brief_title>
  <official_title>A Randomized Double-Blind Controlled Trial of Creatine in Female Methamphetamine Users</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Perry Renshaw</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Methamphetamine (MA) addiction is a public health concern that causes substantial harm to&#xD;
      individual users, and imposes an economic burden in the U.S. totaling up to $48.3 billion&#xD;
      annually. This study proposes to address a critical aspect of this problem: the lack of any&#xD;
      proven, FDA-approved pharmacological treatments for MA users. The proposal combines an&#xD;
      intervention designed to improve energy metabolism in the brain, and a neuroimaging technique&#xD;
      capable of measuring the neurochemicals that represent cerebral bioenergetic function. The&#xD;
      study will replicate and extend a key neuroimaging finding from the investigators recent MA&#xD;
      studies: that MA users have decreased phosphocreatine (PCr) levels in the brain, compared to&#xD;
      healthy volunteers. Phosphocreatine is the substrate reservoir for the creatine kinase&#xD;
      reaction, which reversibly converts PCr into adenosine triphosphate (ATP), the brain's major&#xD;
      energy supply, and creatine. Neuronal energy demands are met through a shift in reaction&#xD;
      equilibrium, which is designed to maintain the concentration of ATP constant. Research&#xD;
      results from the investigators recent study also showed that female MA users have lower brain&#xD;
      PCr levels compared to male users. These findings join the converging lines of evidence that&#xD;
      MA use is associated with mitochondrial dysfunction, i.e. deficient energy metabolism, in the&#xD;
      brain. Frequently, MA users also experience depression, as well as cognitive deficits.&#xD;
      Interestingly, both of these entities are also linked to mitochondrial dysfunction in the&#xD;
      brain.&#xD;
&#xD;
      The long-term goal of this research program is to define the alterations in brain chemistry&#xD;
      that underlie MA use disorders, and to utilize translational magnetic resonance spectroscopy&#xD;
      (MRS) neuroimaging to identify rational brain-based treatment targets. Once a&#xD;
      hypothesis-driven intervention is identified, MRS can then be further employed in treatment&#xD;
      studies, to verify that &quot;target engagement&quot; is achieved. The specific aims of this proposal&#xD;
      are an example of this stepwise scientific process: the nutritional supplement creatine will&#xD;
      be tested in a randomized, placebo-controlled study of women with MA use disorders, to&#xD;
      investigate creatine's effect on cerebral PCr levels, depressive symptoms, and MA usage.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">January 31, 2023</completion_date>
  <primary_completion_date type="Actual">January 31, 2023</primary_completion_date>
  <phase>Phase 4</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>Hamilton Depression Rating Scale (HAMD) scores</measure>
    <time_frame>8-weeks</time_frame>
    <description>Change in HAMD scores will be evaluated over the course of the 8-week treatment period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Beck Anxiety Inventory (BAI) scores</measure>
    <time_frame>8-weeks</time_frame>
    <description>Change in BAI scores will be evaluated over the course of the 8-week treatment period.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Neurochemistry measured by magnetic resonance spectroscopy</measure>
    <time_frame>8-weeks</time_frame>
    <description>Neurochemistry, such as PCr, NAA and GABA, will be measured pre- and post-creatine/placebo treatment.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Depression</condition>
  <condition>Dual Diagnosis</condition>
  <condition>Drug Addiction</condition>
  <arm_group>
    <arm_group_label>Creatine monohydrate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>5 grams of daily creatine monohydrate for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>5 g of placebo for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Creatine monohydrate</intervention_name>
    <arm_group_label>Creatine monohydrate</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female gender, ages 18-55 inclusive&#xD;
&#xD;
          -  Current primary diagnosis of MA dependence or abuse, with MA preferred drug of abuse&#xD;
&#xD;
          -  Current diagnosis of Major Depressive Disorder&#xD;
&#xD;
          -  Current HAMD score &gt; 15&#xD;
&#xD;
          -  Clinical Global Impressions Severity depression score &gt; 4&#xD;
&#xD;
          -  If currently taking a psychotropic medication for depressed mood, regimen must be&#xD;
             stable for &gt; 4 weeks before randomization&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Persons unable to provide adequate consent&#xD;
&#xD;
          -  Persons who are at clinically significant suicidal or homicidal risk&#xD;
&#xD;
          -  Primary substance-related diagnosis other than MA dependence or abuse&#xD;
&#xD;
          -  Comorbid substance dependence diagnosis, other than nicotine (substance abuse&#xD;
             diagnoses are not excluded)&#xD;
&#xD;
          -  Positive pregnancy test&#xD;
&#xD;
          -  Positive test for the antibody to the Human Immunodeficiency Virus (HIV)&#xD;
&#xD;
          -  History of renal disease&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Perry Renshaw, MD, PhD, MBA</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Utah</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 15, 2014</study_first_submitted>
  <study_first_submitted_qc>July 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 17, 2014</study_first_posted>
  <last_update_submitted>May 30, 2023</last_update_submitted>
  <last_update_submitted_qc>May 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Utah</investigator_affiliation>
    <investigator_full_name>Perry Renshaw</investigator_full_name>
    <investigator_title>Professor of Psychiatry</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Substance-Related Disorders</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/NCT02192931
org study id: 73034
nct id: NCT02192931
lead sponsor: 
has dmc: Yes
Methamphetamine (MA) addiction is a public health concern that causes substantial harm to
      individual users, and imposes an economic burden in the U.S. totaling up to $48.3 billion
      annually. This study proposes to address a critical aspect of this problem: the lack of any
      proven, FDA-approved pharmacological treatments for MA users. The proposal combines an
      intervention designed to improve energy metabolism in the brain, and a neuroimaging technique
      capable of measuring the neurochemicals that represent cerebral bioenergetic function. The
      study will replicate and extend a key neuroimaging finding from the investigators recent MA
      studies: that MA users have decreased phosphocreatine (PCr) levels in the brain, compared to
      healthy volunteers. Phosphocreatine is the substrate reservoir for the creatine kinase
      reaction, which reversibly converts PCr into adenosine triphosphate (ATP), the brain's major
      energy supply, and creatine. Neuronal energy demands are met through a shift in reaction
      equilibrium, which is designed to maintain the concentration of ATP constant. Research
      results from the investigators recent study also showed that female MA users have lower brain
      PCr levels compared to male users. These findings join the converging lines of evidence that
      MA use is associated with mitochondrial dysfunction, i.e. deficient energy metabolism, in the
      brain. Frequently, MA users also experience depression, as well as cognitive deficits.
      Interestingly, both of these entities are also linked to mitochondrial dysfunction in the
      brain.

      The long-term goal of this research program is to define the alterations in brain chemistry
      that underlie MA use disorders, and to utilize translational magnetic resonance spectroscopy
      (MRS) neuroimaging to identify rational brain-based treatment targets. Once a
      hypothesis-driven intervention is identified, MRS can then be further employed in treatment
      studies, to verify that "target engagement" is achieved. The specific aims of this proposal
      are an example of this stepwise scientific process: the nutritional supplement creatine will
      be tested in a randomized, placebo-controlled study of women with MA use disorders, to
      investigate creatine's effect on cerebral PCr levels, depressive symptoms, and MA usage.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Hamilton Depression Rating Scale (HAMD) scores
time frame: 8-weeks
description: Change in HAMD scores will be evaluated over the course of the 8-week treatment period.
measure: Beck Anxiety Inventory (BAI) scores
time frame: 8-weeks
description: Change in BAI scores will be evaluated over the course of the 8-week treatment period.
measure: Neurochemistry measured by magnetic resonance spectroscopy
time frame: 8-weeks
description: Neurochemistry, such as PCr, NAA and GABA, will be measured pre- and post-creatine/placebo treatment.
arm group label: Creatine monohydrate
arm group type: Active Comparator
description: 5 grams of daily creatine monohydrate for 8 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: 5 g of placebo for 8 weeks
arm group label: Healthy Control
arm group type: No Intervention
intervention type: Drug
intervention name: Creatine monohydrate
arm group label: Creatine monohydrate
arm group label: Placebo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Perry Renshaw, MD, PhD, MBA
role: Principal Investigator
affiliation: University of Utah
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Utah
investigator full name: Perry Renshaw
investigator title: Professor of Psychiatry
mesh term: Substance-Related Disorders