Clinical trial NCT03265808: Allogeneic Human Mesenchymal Stem Cell Infusion vs Placebo in Alcohol Use Disorder and Major Depression.
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Major Depressive Disorder
Alcohol Use Disorder
Keywords: stem cells
Lead sponsor: University of Texas Rio Grande Valley
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2017-08-29
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility 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.

Primary outcomes:
measure: Incident of treatment emergent-serious adverse events
timeFrame: One month post-infusion
Secondary outcomes:
measure: Change in serum concentrations of high sensitivity C-reactive protein.
timeFrame: Baseline, 12 weeks
measure: Change in serum concentrations of inflammatory biomarkers
timeFrame: Baseline, 12 weeks
measure: Change in depressive symptoms as assessed by MADRS
timeFrame: Baseline, 12 weeks
measure: Change in Depressive symptoms as assessed by CGI
timeFrame: Baseline, 12 weeks
measure: Change in quantity of alcohol use as assessed by TLFB
timeFrame: Baseline, 12 weeks
measure: Change in frequency of alcohol use as assessed by TLFB
timeFrame: Baseline, 12 weeks
measure: Change in Anhedonia as measured by SHAPS
timeFrame: Baseline, 12 weeks
measure: Change in cravings as assessed by AUQ
timeFrame: Baseline, 12 weeks
measure: Change in cravings as assessed by OCDS
timeFrame: Baseline, 12 weeks
measure: Change in cognition as assessed by BAC-A
timeFrame: Baseline, 12 weeks
measure: Change in functioning as assessed by UPSA-B
timeFrame: Baseline, 12 weeks
measure: Change in functioning as assessed by GAF
timeFrame: Baseline, 12 weeks
measure: Change in quality of life as assessed by QOLI
timeFrame: Baseline, 12 weeks
Other outcomes:
Locations:
city: Harlingen
country: United States
facility: University of Texas Rio Grande Valley School of Medicine
state: Texas
Study officials:
affiliation: University of Texas Rio Grande Valley School of Medicine
name: Ihsan Salloum, MD
role: PRINCIPAL_INVESTIGATOR
References: