<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/NCT03265808</url>
  </required_header>
  <id_info>
    <org_study_id>20170674</org_study_id>
    <secondary_id>1R01AA024933-01A1</secondary_id>
    <nct_id>NCT03265808</nct_id>
  </id_info>
  <brief_title>Allogeneic Human Mesenchymal Stem Cell Infusion vs Placebo in Alcohol Use Disorder and Major Depression.</brief_title>
  <acronym>Alaunus</acronym>
  <official_title>A Phase I/II, Prospective, Randomized, Double-Blind, PlAcebo-ControLled Trial to EvAluate the Efficacy of Allogeneic HUman Mesenchymal Stem Cell InfusioN Versus Placebo in Subjects With Alcohol Use Disorder and Major DepreSsion.(ALAUNUS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ihsan M Salloum, MD, MPH</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Texas Rio Grande Valley</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to look at the safety of a study treatment with stem cells in&#xD;
      Alcohol Use Disorder And Major Depression (AUD-MD) subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind placebo-controlled study of allogeneic human mesenchymal&#xD;
      stem cell in subjects with comorbid Alcohol Use Disorder And Major Depression (AUD-MD). 80&#xD;
      subjects will be randomized (1:1) to active treatment vs. placebo an followed weekly for 12&#xD;
      weeks and then every 3 months for 12 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 18, 2018</start_date>
  <completion_date type="Anticipated">April 2025</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</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>Incident of treatment emergent-serious adverse events</measure>
    <time_frame>One month post-infusion</time_frame>
    <description>Incidence of any treatment-emergent serious adverse events, defined as a composite of acute suicidality and hospitalization for suicide attempts.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in serum concentrations of high sensitivity C-reactive protein.</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Change in serum concentrations of high sensitivity C-reactive protein. A serum sample will be collected to assess the change.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum concentrations of inflammatory biomarkers</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Change in serum concentrations of inflammatory biomarkers, such as in TNF alpha and interleukin-6. A serum sample will be collected to assess the change.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in depressive symptoms as assessed by MADRS</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Montgomery and Asberg Depression Rating Scale (MADRS) is a ten item questionnaire with a total score ranging from 0-60 with a higher score indicating higher depressive symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Depressive symptoms as assessed by CGI</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Clinical Global Improvement (CGI) is rated on a 7 point scale ranging from 1 (very much improved) to 7 (very much worse).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quantity of alcohol use as assessed by TLFB</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>30-day self report Timeline Follow Back (TLFB) questionnaire will be used to assess daily alcohol use.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in frequency of alcohol use as assessed by TLFB</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>30-day self report Timeline Follow Back (TLFB) questionnaire will be used to assess frequency of daily alcohol use.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Anhedonia as measured by SHAPS</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Snaith Hamilton Pleasure Scale (SHAPS) is a 14 item questionnaire with a total score ranging from 0-56 with a higher score indicating increased anhedonic symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cravings as assessed by AUQ</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Alcohol Urge Questionnaire (AUQ) is an 8 item questionnaire with total score ranging from 8-56 with a high score indicating increased cravings .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cravings as assessed by OCDS</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Obsessive-Compulsive Drinking Scale (OCDS) is a 14 item questionnaire ranging from 0-56 with a higher score indicating increase cravings.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cognition as assessed by BAC-A</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Brief Assessment of Cognition for Affective Disorders (BAC-A) includes brief assessments of executive functions, verbal fluency, attention, verbal memory, working memory and motor speed. Z-scores are calculated from composite scores. Higher z-scores are indicative of better cognitive performance, lower z-scores are indicative of lower cognitive performance. Range of z-scores anticipated to be between -3 and 3.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in functioning as assessed by UPSA-B</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>University of California of San Diego (UCSD) Performance Based Skills Assessment (UPSA-B) questionnaire has a total score from 0-100 with a higher score indication better functioning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in functioning as assessed by GAF</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Global Assessment of Functioning (GAF) questionnaire has a total score ranging from 1-100 with a higher score indicating of daily activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life as assessed by QOLI</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>Quality of Life Index (QOLI) questionnaire has a total score ranging from 10-100 with a higher score indicating higher quality of life.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Major Depressive Disorder</condition>
  <condition>Alcohol Use Disorder</condition>
  <arm_group>
    <arm_group_label>allogeneic human mesenchymal stem cells (allo-hMSCs)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be treated with a single administration of allogeneic hMSCs: 100 x 10^6 (100 million) allo-hMSCs of cells delivered via a single peripheral intravenous infusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be treated with a placebo administration consisting of 1% human albumin serum in Plasma-Lyte A delivered via a single peripheral intravenous infusion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>allogeneic human mesenchymal stem cells (allo-hMSCs)</intervention_name>
    <description>Single administration of allogeneic hMSCs: 100 x 106 (100 million) allo-hMSCs of cells delivered via a single peripheral intravenous infusion.</description>
    <arm_group_label>allogeneic human mesenchymal stem cells (allo-hMSCs)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo administration consisting of 1% human albumin serum in Plasma-Lyte A delivered via a single peripheral intravenous infusion.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provide written informed consent.&#xD;
&#xD;
          2. Subjects age &gt;18 and &lt;75 years at the time of signing the Informed Consent Form.&#xD;
&#xD;
          3. Diagnostic and Statistical Manual of Mental Disorder-5 criteria for Alcohol Urge&#xD;
             Questionnaire (moderate or severe defined as meeting 4 or more of the 11 criteria) AND&#xD;
             a concurrent Diagnostic and Statistical Manual of Mental Disorder-5 recurrent unipolar&#xD;
             major depression with HRSD-25 score of 18 or above.&#xD;
&#xD;
          4. A history of a depressive episode occurring or persisting during a period of one-month&#xD;
             abstinence.&#xD;
&#xD;
          5. Participants should express the desire to reduce or stop alcohol consumption, report&#xD;
             28 or more standard drinks (SD) per week for males or 21 for females over four weeks&#xD;
             during the 90 days preceding study enrollment.&#xD;
&#xD;
          6. Increased inflammation ([serum C-reactive protein] ≥3.0 mg/L.&#xD;
&#xD;
          7. Agree to taper and discontinue antidepressant medications during the 12-week trial.&#xD;
&#xD;
          8. Able to provide informed consent and comply with study procedures.&#xD;
&#xD;
          9. Able to read English and understand study instruments.&#xD;
&#xD;
         10. Entry criteria for depression and alcohol use disorder (moderate or severe) will be&#xD;
             established using the Structured Clinical Interview for Diagnostic and Statistical&#xD;
             Manual of Mental Disorders (SCID) for categorical diagnosis.&#xD;
&#xD;
         11. Have a score of ≥18 on the Hamilton Depression Rating Scale for Depression (HAM-D).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Acute suicidality.&#xD;
&#xD;
          2. Any lifetime history of bipolar disorder, schizophrenia, or schizoaffective disorder.&#xD;
&#xD;
          3. Active psychotic disorder, eating disorder, or substance use disorder except for&#xD;
             alcohol and tobacco or &quot;mild&quot; cannabis use disorder within 6 months of enrollment.&#xD;
&#xD;
          4. Any lifetime history of autoimmune or immunodeficiency syndrome.&#xD;
&#xD;
          5. Treatment with any psychotropic (including hypnotic), steroidal, or anti-inflammatory&#xD;
             medication (including NSAIDs) within 2 weeks of treatment randomization (6 weeks for&#xD;
             fluoxetine).&#xD;
&#xD;
          6. Any current use of medication that affect alcohol consumption such as acamprosate,&#xD;
             disulfiram, naltrexone (po or IM), topiramate, or sedative-hypnotics including&#xD;
             benzodiazepines or any psychostimulant.&#xD;
&#xD;
          7. Being enrolled in an alcohol treatment program (self-help groups participation such as&#xD;
             Alcoholics Anonymous or Dual Diagnosis self-help are allowed).&#xD;
&#xD;
          8. Active medical condition that could cause or exacerbate depressive symptoms (e.g.,&#xD;
             hypothyroidism, anemia).&#xD;
&#xD;
          9. Currently pregnant or breast-feeding.&#xD;
&#xD;
         10. Lack of use of a reliable means of contraception methods. (Female subjects of&#xD;
             childbearing potential must undergo a serum or urine pregnancy test at screening and&#xD;
             within 36 hours prior to infusion.)&#xD;
&#xD;
         11. First major depressive episode after 50 years of age.&#xD;
&#xD;
         12. Any evidence of current infection including serum positive for HIV, hepatitis BsAg or&#xD;
             Viremic hepatitis.&#xD;
&#xD;
         13. Medical conditions with known autoimmune or inflammatory mechanisms including any&#xD;
             chronic allergic condition.&#xD;
&#xD;
         14. Positive urine screens for any drug of abuse other than cannabis at baseline.&#xD;
&#xD;
         15. Inability to read or understand study forms or informed consent or the presence of any&#xD;
             other conditions or factors, which in the opinion of the investigator would make the&#xD;
             patient unsuitable for study participation.&#xD;
&#xD;
         16. Prior history of a suicide attempt, within the past year.&#xD;
&#xD;
         17. Have hypersensitivity to dimethyl sulfoxide (DMSO).&#xD;
&#xD;
         18. Have a clinical history of malignancy within 3 years (i.e., subjects with prior&#xD;
             malignancy must be disease free for 3 years), except curatively-treated basal cell&#xD;
             carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma.&#xD;
&#xD;
         19. Be serum positive for HIV, hepatitis BsAg or Viremic hepatitis C.&#xD;
&#xD;
         20. Be currently participating (or participated within the previous 30 days) in an&#xD;
             investigational therapeutic or device trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ihsan Salloum, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas Rio Grande Valley School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas Rio Grande Valley School of Medicine</name>
      <address>
        <city>Harlingen</city>
        <state>Texas</state>
        <zip>78550</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>November 14, 2022</last_update_submitted>
  <last_update_submitted_qc>November 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Texas Rio Grande Valley</investigator_affiliation>
    <investigator_full_name>Ihsan M Salloum, MD, MPH</investigator_full_name>
    <investigator_title>Sponsor</investigator_title>
  </responsible_party>
  <keyword>stem cells</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
    <mesh_term>Alcohol Drinking</mesh_term>
  </condition_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/NCT03265808
org study id: 20170674
secondary id: 1R01AA024933-01A1
nct id: NCT03265808
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to look at the safety of a study treatment with stem cells in
      Alcohol Use Disorder And Major Depression (AUD-MD) subjects.
This is a randomized, double-blind placebo-controlled study of allogeneic human mesenchymal
      stem cell in subjects with comorbid Alcohol Use Disorder And Major Depression (AUD-MD). 80
      subjects will be randomized (1:1) to active treatment vs. placebo an followed weekly for 12
      weeks and then every 3 months for 12 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Incident of treatment emergent-serious adverse events
time frame: One month post-infusion
description: Incidence of any treatment-emergent serious adverse events, defined as a composite of acute suicidality and hospitalization for suicide attempts.
measure: Change in serum concentrations of high sensitivity C-reactive protein.
time frame: Baseline, 12 weeks
description: Change in serum concentrations of high sensitivity C-reactive protein. A serum sample will be collected to assess the change.
measure: Change in serum concentrations of inflammatory biomarkers
time frame: Baseline, 12 weeks
description: Change in serum concentrations of inflammatory biomarkers, such as in TNF alpha and interleukin-6. A serum sample will be collected to assess the change.
measure: Change in depressive symptoms as assessed by MADRS
time frame: Baseline, 12 weeks
description: Montgomery and Asberg Depression Rating Scale (MADRS) is a ten item questionnaire with a total score ranging from 0-60 with a higher score indicating higher depressive symptoms.
measure: Change in Depressive symptoms as assessed by CGI
time frame: Baseline, 12 weeks
description: Clinical Global Improvement (CGI) is rated on a 7 point scale ranging from 1 (very much improved) to 7 (very much worse).
measure: Change in quantity of alcohol use as assessed by TLFB
time frame: Baseline, 12 weeks
description: 30-day self report Timeline Follow Back (TLFB) questionnaire will be used to assess daily alcohol use.
measure: Change in frequency of alcohol use as assessed by TLFB
time frame: Baseline, 12 weeks
description: 30-day self report Timeline Follow Back (TLFB) questionnaire will be used to assess frequency of daily alcohol use.
measure: Change in Anhedonia as measured by SHAPS
time frame: Baseline, 12 weeks
description: Snaith Hamilton Pleasure Scale (SHAPS) is a 14 item questionnaire with a total score ranging from 0-56 with a higher score indicating increased anhedonic symptoms.
measure: Change in cravings as assessed by AUQ
time frame: Baseline, 12 weeks
description: Alcohol Urge Questionnaire (AUQ) is an 8 item questionnaire with total score ranging from 8-56 with a high score indicating increased cravings .
measure: Change in cravings as assessed by OCDS
time frame: Baseline, 12 weeks
description: Obsessive-Compulsive Drinking Scale (OCDS) is a 14 item questionnaire ranging from 0-56 with a higher score indicating increase cravings.
measure: Change in cognition as assessed by BAC-A
time frame: Baseline, 12 weeks
description: Brief Assessment of Cognition for Affective Disorders (BAC-A) includes brief assessments of executive functions, verbal fluency, attention, verbal memory, working memory and motor speed. Z-scores are calculated from composite scores. Higher z-scores are indicative of better cognitive performance, lower z-scores are indicative of lower cognitive performance. Range of z-scores anticipated to be between -3 and 3.
measure: Change in functioning as assessed by UPSA-B
time frame: Baseline, 12 weeks
description: University of California of San Diego (UCSD) Performance Based Skills Assessment (UPSA-B) questionnaire has a total score from 0-100 with a higher score indication better functioning.
measure: Change in functioning as assessed by GAF
time frame: Baseline, 12 weeks
description: Global Assessment of Functioning (GAF) questionnaire has a total score ranging from 1-100 with a higher score indicating of daily activities.
measure: Change in quality of life as assessed by QOLI
time frame: Baseline, 12 weeks
description: Quality of Life Index (QOLI) questionnaire has a total score ranging from 10-100 with a higher score indicating higher quality of life.
arm group label: allogeneic human mesenchymal stem cells (allo-hMSCs)
arm group type: Experimental
description: Participants will be treated with a single administration of allogeneic hMSCs: 100 x 10^6 (100 million) allo-hMSCs of cells delivered via a single peripheral intravenous infusion.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will be treated with a placebo administration consisting of 1% human albumin serum in Plasma-Lyte A delivered via a single peripheral intravenous infusion.
intervention type: Drug
intervention name: allogeneic human mesenchymal stem cells (allo-hMSCs)
description: Single administration of allogeneic hMSCs: 100 x 106 (100 million) allo-hMSCs of cells delivered via a single peripheral intravenous infusion.
arm group label: allogeneic human mesenchymal stem cells (allo-hMSCs)
intervention type: Drug
intervention name: Placebo
description: Placebo administration consisting of 1% human albumin serum in Plasma-Lyte A delivered via a single peripheral intravenous infusion.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Ihsan Salloum, MD
role: Principal Investigator
affiliation: University of Texas Rio Grande Valley School of Medicine
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Texas Rio Grande Valley
investigator full name: Ihsan M Salloum, MD, MPH
investigator title: Sponsor
mesh term: Alcoholism
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Alcohol Drinking
sharing ipd: No