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Allogeneic HUman Mesenchymal Stem Cell InfusioN Versus Placebo in Subjects With Alcohol Use Disorder and Major DepreSsion. (Alaunus)

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ClinicalTrials.gov Identifier: NCT03265808
Recruitment Status : Recruiting
First Posted : August 29, 2017
Last Update Posted : January 12, 2018
Sponsor:
Collaborator:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Information provided by (Responsible Party):
Joshua M Hare, University of Miami

Brief Summary:
Eighty (80) subjects with Alcohol Use Disorder and Comorbid Major Depression, fulfilling all inclusion/exclusion criteria's will be randomly assigned to receive allogeneic human Mesenchymal stem cells or placebo in a 1:1 blinded fashion.

Condition or disease Intervention/treatment Phase
Major Depression Alcohol Use Disorder Drug: allogeneic human mesenchymal stem cells (allo-hMSCs) Drug: Placebo Phase 1 Phase 2

Detailed Description:

Eighty (80) subjects fulfilling all inclusion/exclusion criteria's will be randomly assigned to receive allogeneic hMSCs or placebo in a 1:1 blinded fashion.

Forty (40) subjects 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.

Forty (40) subjects will be treated with a placebo administration consisting of 1% human albumin serum in Plasma-Lyte A delivered via a single peripheral intravenous infusion.

The Allo-hMSCs will be supplied from an allogeneic human mesenchymal stem cell source or commercial grade bone marrow product and will be manufactured by the University of Miami.

The study will last approximately 14 months with six follow-up visits, which will occur every 2 weeks at 2, 4, 6, 8, 10, and 12 weeks following treatment infusion and then at 6, 9 and 12 months.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be randomized in a 1:1 blinded fashion
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase I/II, Prospective, Randomized, Double-Blind, PlAcebo-ControLled Trial to EvAluate the Potential Efficacy of Allogeneic HUman Mesenchymal Stem Cell InfusioN Versus Placebo in Subjects With Alcohol Use Disorder and Major DepreSsion.
Estimated Study Start Date : June 2018
Estimated Primary Completion Date : February 2025
Estimated Study Completion Date : February 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Alcohol
U.S. FDA Resources

Arm Intervention/treatment
Experimental: allogeneic human mesenchymal stem cells (allo-hMSCs)
Forty (40) subjects 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.
Drug: allogeneic human mesenchymal stem cells (allo-hMSCs)
Forty (40) subjects will be treated with a single administration of allogeneic hMSCs: 100 x 106 (100 million) allo-hMSCs of cells delivered via a single peripheral intravenous infusion.
Other Names:
  • allo-hMSCs
  • stem cells
Placebo Comparator: Placebo
Forty (40) subjects will be treated with a placebo administration consisting of 1% human albumin serum in Plasma-Lyte A delivered via a single peripheral intravenous infusion.
Drug: Placebo
Forty (40) subjects will be treated with a placebo administration consisting of 1% human albumin serum in Plasma-Lyte A delivered via a single peripheral intravenous infusion.



Primary Outcome Measures :
  1. treatment emergent-serious adverse events [ Time Frame: One month post-infusion ]
    Incidence (at one-month post infusion) of any treatment-emergent serious adverse events, defined as a composite of acute suicidality and hospitalization for suicide attempts.


Secondary Outcome Measures :
  1. Reduction of Inflammation [ Time Frame: Assessed at 12 weeks ]
    Reduction of Inflammation: Change in serum concentrations of high sensitivity C-reactive protein. A serum sample will be collected to assess the change.

  2. Reduction of Inflammation [ Time Frame: Assessed at 12 weeks ]
    Reduction of Inflammation: 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.

  3. Reduction in Depressive Symptoms [ Time Frame: Assessed at 12 weeks ]
    Reduction in Depressive Symptoms due to change in MADRS.

  4. Reduction in Depressive Symptoms [ Time Frame: Assessed at 12 weeks ]
    Reduction in Depressive Symptoms due to change in Global clinical functioning (CGI).

  5. Reduction of alcohol use [ Time Frame: Assessed at 12 weeks ]
    Reduction of alcohol use using the clinician administered measures of the severity of alcohol use (TLFB-% heavy drinking days)

  6. Reduction in Anhedonia [ Time Frame: Assessed at 12 weeks ]
    Reduction in Anhedonia (depression related features) due to change in SHAPS.

  7. Improvements in quality of life [ Time Frame: Assessed at 12 weeks ]
    Improvements in craving, cognition, functioning and quality of life as indicated by changes in the Alcohol Urge Questionnaire.

  8. Improvements in quality of life [ Time Frame: Assessed at 12 weeks ]
    Improvements in craving, cognition, functioning and quality of life as indicated by changes in the Obsessive-Compulsive Drinking Scale.

  9. Improvements in quality of life [ Time Frame: Assessed at 12 weeks ]
    Improvements in craving, cognition, functioning and quality of life as indicated by changes in the Brief Assessment of Cognition for Affective Disorders.

  10. Improvements in quality of life [ Time Frame: Assessed at 12 weeks ]
    Improvements in craving, cognition, functioning and quality of life as indicated by changes in the UCSD Performance Based Skills Assessment.

  11. Improvements in quality of life [ Time Frame: Assessed at 12 weeks ]
    Improvements in craving, cognition, functioning and quality of life as indicated by changes in the Global Assessment of Functioning questionnaire.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provide written informed consent.
  2. Subjects age >18 and <75 years at the time of signing the Informed Consent Form.
  3. Diagnostic and Statistical Manual of Mental Disorder-5 criteria for Alcohol Urge Questionnaire (moderate or severe defined as meeting 4 or more of the 11 criteria) AND a concurrent Diagnostic and Statistical Manual of Mental Disorder-5 recurrent unipolar major depression with HRSD-25 score of 18 or above.
  4. A history of a depressive episode occurring or persisting during a period of one-month abstinence.
  5. Participants should express the desire to reduce or stop alcohol consumption, report 28 or more standard drinks (SD) per week for males or 21 for females over four weeks during the 90 days preceding study enrollment.
  6. Increased inflammation ([serum C-reactive protein] ≥3.0 mg/L.
  7. Agree to taper and discontinue antidepressant medications during the 12-week trial.
  8. Able to provide informed consent and comply with study procedures.
  9. Able to read English and understand study instruments.
  10. Entry criteria for depression and alcohol use disorder (moderate or severe) will be established using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID) for categorical diagnosis.
  11. Have a score of ≥18 on the Hamilton Depression Rating Scale for Depression (HAM-D).

Exclusion Criteria:

  1. Acute suicidality.
  2. Any lifetime history of bipolar disorder, schizophrenia, or schizoaffective disorder.
  3. Active psychotic disorder, eating disorder, or substance use disorder except for alcohol and tobacco or "mild" cannabis use disorder within 6 months of enrollment.
  4. Any lifetime history of autoimmune or immunodeficiency syndrome.
  5. Treatment with any psychotropic (including hypnotic), steroidal, or anti-inflammatory medication (including NSAIDs) within 2 weeks of treatment randomization (6 weeks for fluoxetine).
  6. Any current use of medication that affect alcohol consumption such as acamprosate, disulfiram, naltrexone (po or IM), topiramate, or sedative-hypnotics including benzodiazepines or any psychostimulant.
  7. Being enrolled in an alcohol treatment program (self-help groups participation such as Alcoholics Anonymous or Dual Diagnosis self-help are allowed).
  8. Active medical condition that could cause or exacerbate depressive symptoms (e.g., hypothyroidism, anemia).
  9. Currently pregnant or breast-feeding.
  10. Lack of use of a reliable means of contraception methods. (Female subjects of childbearing potential must undergo a serum or urine pregnancy test at screening and within 36 hours prior to infusion.)
  11. First major depressive episode after 50 years of age.
  12. Any evidence of current infection including serum positive for HIV, hepatitis BsAg or Viremic hepatitis.
  13. Medical conditions with known autoimmune or inflammatory mechanisms including any chronic allergic condition.
  14. Positive urine screens for any drug of abuse other than cannabis at baseline.
  15. Inability to read or understand study forms or informed consent or the presence of any other conditions or factors, which in the opinion of the investigator would make the patient unsuitable for study participation.
  16. Prior history of a suicide attempt, within the past year.
  17. Have hypersensitivity to dimethyl sulfoxide (DMSO).
  18. Have a clinical history of malignancy within 3 years (i.e., subjects with prior malignancy must be disease free for 3 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma.
  19. Be serum positive for HIV, hepatitis BsAg or Viremic hepatitis C.
  20. Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03265808


Contacts
Contact: Joshua M Hare, MD 305-243-5579 JHare@med.miami.edu

Locations
United States, Florida
Interdisciplinary stem cell institute (ISCI) Recruiting
Miami, Florida, United States, 33136
Contact: Belinda Robertson    305-243-2891    BRobertson@med.miami.edu   
Contact: Study Coordinators    305-243-2891    ISCIStudyInfo@miami.edu   
Principal Investigator: Ihsan Salloum, MD         
Sponsors and Collaborators
Joshua M Hare
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Investigators
Principal Investigator: Ihsan Salloum, MD University of Miami

Additional Information:
Responsible Party: Joshua M Hare, Sponsor, University of Miami
ClinicalTrials.gov Identifier: NCT03265808     History of Changes
Other Study ID Numbers: 20170674
1R01AA024933-01A1 ( U.S. NIH Grant/Contract )
First Posted: August 29, 2017    Key Record Dates
Last Update Posted: January 12, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Joshua M Hare, University of Miami:
stem cells

Additional relevant MeSH terms:
Disease
Depression
Depressive Disorder
Depressive Disorder, Major
Alcohol Drinking
Pathologic Processes
Behavioral Symptoms
Mood Disorders
Mental Disorders
Drinking Behavior