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Psilocybin Treatment of Major Depressive Disorder With Co-occurring Alcohol Use Disorder (PsiloMDDAUD)

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ClinicalTrials.gov Identifier: NCT04620759
Recruitment Status : Recruiting
First Posted : November 9, 2020
Last Update Posted : April 15, 2021
Sponsor:
Information provided by (Responsible Party):
Johns Hopkins University

Tracking Information
First Submitted Date  ICMJE November 3, 2020
First Posted Date  ICMJE November 9, 2020
Last Update Posted Date April 15, 2021
Actual Study Start Date  ICMJE April 14, 2021
Estimated Primary Completion Date August 31, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 3, 2020)
  • Change from baseline in grid-version of the Hamilton Depression Rating Scale (GRID-HAMD) score [ Time Frame: Baseline and 1 month after first experimental drug administration session ]
    The GRID-Hamilton Depression Rating Scale is a 17-item clinician-administered rating scale designed to assess severity of depressive symptoms. The score range for the GRID-HAMD is 0 to 52, with higher score indicating more severe depression.
  • Change from baseline in percentage of days abstinent as measured by the Time Line Follow Back (TLFB) assessment [ Time Frame: Baseline and 3 months after first experimental drug administration session ]
    The TLFB is a widely used, standardized, calendar-based retrospective self-report assessment to quantify daily alcohol use. The investigators will examine the primary outcome of percentage of abstinent days in the past 90 days.
  • Change from baseline in percentage of days of heavy drinking as measured by the TLFB assessment [ Time Frame: Baseline and 3 months after first experimental drug administration session ]
    The TLFB is a widely used, standardized, calendar-based retrospective self-report assessment to quantify daily alcohol use. The investigators will examine the primary outcome of percentage of drinking days in the past 90 days.
  • Change from baseline in gamma-glutamyl transferase (GGT) [ Time Frame: Baseline and 3 months after first experimental drug administration session ]
    Change in GGT (IU/L) will be measured by peripheral blood tests. GGT is elevated in chronic drinkers. Elevated GGT due to drinking can begin to reduce after a week of abstinence, and can return to normal levels after roughly 4 weeks of abstinence.
  • Change from baseline in the percentage of carbohydrate deficient transferrin relative to total transferrin concentration (%CDT) [ Time Frame: Baseline and 3 months after first experimental drug administration session ]
    Change in %CDT will be measured by peripheral blood tests. %CDT can become elevated after 1 to 2 weeks of heavy drinking, and can return to normal levels within 2 weeks of abstinence.
  • Change from baseline in the ratio of aspartate transaminase to alanine transaminase (AST/ALT) [ Time Frame: Baseline and 3 months after first experimental drug administration session ]
    Change in AST/ALT ratio will be measured by peripheral blood tests. Elevated AST/ALT ratio has been associated with heavy drinking, and can return to normal levels after extended abstinence.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 3, 2020)
  • Change from baseline in Quick Inventory of Depressive Symptomatology - Self Rated (QIDS-SR) score [ Time Frame: Baseline, 1 week, 1 month, and 3 month post-drug-session visits; 6 and 12 month follow-ups after the second experimental drug administration session. ]
    The Quick Inventory of Depressive Symptomatology is a 16-item self-report questionnaire that measures the nine symptom domains of a depressive episode, with higher scores indicating greater depression severity. This questionnaire is rated on a scale of 0 to 3. These values represent varying answers for each item and can be found within the questionnaire.
  • Change from baseline in State Trait Anxiety Index (STAI) score [ Time Frame: Baseline, 1 week, 1 month, and 3 month post-drug-session visits; 6 and 12 month follow-ups after the second experimental drug administration session ]
    The STAI is a 40-item self-report measure that assessing anxiety on two different scales: State and Trait. State anxiety is scored on a 4-point scale (1 = Not at all; 2 = Somewhat; 3 = Moderately so; 4 = Very much so) and Trait anxiety is scored on the 4-point scale (1 = Almost never; 2 = Sometimes; 3 = Often; 4 = Almost always).
  • Change from baseline in percentage of days abstinent as measured by the TLFB assessment [ Time Frame: Baseline, 1 month post drug administration session, 3 months after the second (unblinded) drug administration session, and at 6 and 12 months post second (unblinded) drug administration session ]
    The TLFB is a widely used, standardized, calendar-based retrospective self-report assessment to quantify daily alcohol use. The investigators will examine the secondary outcome of percentage of abstinent days either within the last 30 days or the last 90 days, depending on study visit.
  • Change from baseline in percentage of days of heavy drinking as measured by the TLFB assessment [ Time Frame: Baseline, 1 month post drug administration session, 3 months after the second (unblinded) drug administration session, and at 6 and 12 months post second (unblinded) drug administration session ]
    The TLFB is a widely used, standardized, calendar-based retrospective self-report assessment to quantify daily alcohol use. The investigators will examine the secondary outcome of percentage of drinking days either within the last 30 days or the last 90 days, depending on study visit.
  • Change from baseline in GGT [ Time Frame: Baseline, 1 month post drug administration session, 3 months after the second (unblinded) drug administration session ]
    Change in GGT (IU/L) will be measured by peripheral blood tests. GGT is elevated in chronic drinkers. Elevated GGT due to drinking can begin to reduce after a week of abstinence, and can return to normal levels after roughly 4 weeks of abstinence.
  • Change from baseline in %CDT [ Time Frame: Baseline, 1 month post drug administration session, 3 months after the second (unblinded) drug administration session ]
    Change in %CDT will be measured by peripheral blood tests. %CDT can become elevated after 1 to 2 weeks of heavy drinking, and can return to normal levels within 2 weeks of abstinence.
  • Change from baseline in AST/ALT ratio [ Time Frame: Baseline, 1 month post drug administration session, 3 months after the second (unblinded) drug administration session ]
    Change in AST/ALT ratio will be measured by peripheral blood tests. Elevated AST/ALT ratio has been associated with heavy drinking, and can return to normal levels after extended abstinence.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Psilocybin Treatment of Major Depressive Disorder With Co-occurring Alcohol Use Disorder
Official Title  ICMJE Psilocybin Treatment of Major Depressive Disorder With Co-occurring Alcohol Use Disorder
Brief Summary The purpose of this study is to determine whether psilocybin, a hallucinogenic drug, is effective in reducing depressive symptoms and amount of drinking in patients with co-occurring Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD).
Detailed Description The objectives of this double-blind, placebo-controlled study are to test the hypotheses that a single high (25 mg) oral dose of psilocybin will lead to enduring reductions in depressive symptoms (as measured by the clinician-rated grid version of the Hamilton Depression Rating Scale, or GRID-HAMD) and amount of drinking (as measured using the Time Line Follow Back, or TLFB, procedure) compared to placebo in patients with co-occurring MDD and AUD. 90 male and female volunteers who are between the ages of 21 and 65 years old and who meet Diagnostic and Statistical Manual, Fifth Edition (DSM-5) criteria for MDD and AUD will be recruited from the community and complete all study procedures. Volunteers will be randomized to one of two study arms (psilocybin [N=45] or placebo [N=45]), and will complete a drug administration session paired with a brief Motivational Interviewing intervention for alcohol use. Volunteers will undergo assessments of depression and alcohol use before and after treatment. After primary endpoints are measured, all volunteers will receive a second, unblinded intervention with a single high dose of psilocybin (25 mg) to test a secondary hypothesis that two doses of psilocybin are more effective in treating MDD with co-occurring AUD than a single dose.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
During the first phase of the study, participants will receive either placebo or treatment and all parties will be blinded. During the second phase of the study, all participants will receive treatment (open label).
Primary Purpose: Treatment
Condition  ICMJE
  • Major Depressive Disorder
  • Alcohol Use Disorder
Intervention  ICMJE
  • Drug: Psilocybin
    The psilocybin used in this study is synthetically manufactured and formulated under current good manufacturing practices (cGMP). The active drug is encapsulated using a size 0 blue gelatin capsule and contains 25 mg of psilocybin.
    Other Name: 4-phosphoryloxy-N,N-dimethyltryptamine
  • Drug: Placebo
    The placebo used in this study is microcrystalline cellulose, an inert substance, encapsulated using a size 0 blue gelatin capsule.
Study Arms  ICMJE
  • Experimental: Psilocybin Treatment
    Participants will be administered 25mg of psilocybin in a clinical setting. Psilocybin is administered orally as a capsule and taken with water.
    Intervention: Drug: Psilocybin
  • Placebo Comparator: Placebo
    Participants will be administered placebo in a clinical setting. Placebo is administered orally as a capsule taken with water.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 3, 2020)
90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 31, 2026
Estimated Primary Completion Date August 31, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 21 to 65 years old
  • Fluent in English
  • Have given written informed consent
  • Have at least a high-school level of education or equivalent (e.g. GED).
  • Have a baseline GRID-HAMD score ≥ 18.
  • Have a confirmed DSM-5 diagnosis of Major Depressive Disorder and currently experiencing a major depressive episode.
  • Have a confirmed DSM-5 diagnosis of mild or moderate Alcohol Use Disorder.
  • Have undergone some form of therapy for MDD or AUD in the past, but are not interested in initiating standard pharmacotherapies for major depressive disorder or alcohol use disorder (e.g. selective serotonin reuptake inhibitor, disulfiram, naloxone, etc.).
  • No antidepressant medication for at least 2 weeks (4 weeks for fluoxetine) prior to enrollment.
  • Be judged by study team clinicians to be at low risk for suicidality
  • Average of at least 1 non-drinking day/week in the past 30 days
  • Have at least 2 heavy drinking days in the past 30 days
  • Concurrent psychotherapy is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening and is expected to remain stable during participation in the study.
  • Be medically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests
  • Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on session days.
  • Agree to refrain from using any psychoactive drugs, including nicotine, within 24 hours of each drug administration. The exception is caffeine.
  • Agree not to take any "as needed" medications on the mornings of drug sessions
  • Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration.
  • Agree to use effective methods of contraception during the study (females).
  • Agree that for one week before each drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals.
  • Have limited lifetime use of hallucinogens (the following criteria are preferred: no use in the past 5 years; total hallucinogen use less than 10 times)

Exclusion Criteria:

  • Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing; women who are of child-bearing potential and sexually active who are not practicing an effective means of contraception.
  • Blood liver tests assessed at screening that are outside of 3x the normal range
  • Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g., atrial fibrilation), prolonged corrected QT (QTc) interval (i.e., QTc > 450 msec), artificial heart valve, or transient ischemic attack in the past year
  • Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) score > 9, or any other indication that the volunteer may experience medically complicated withdrawal from alcohol
  • Epilepsy with history of seizures
  • Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
  • Currently taking psychoactive prescription medication on a regular (e.g., daily) basis
  • Currently taking on a regular (e.g., daily) basis any medications having a primary centrally-acting serotonergic effect, including mono-amine oxidase inhibitors (MAOIs). For individuals who have intermittent or "as-needed" use of such medications, psilocybin sessions will not be conducted until at least 5 half-lives of the agent have elapsed after the last dose.
  • Currently taking medications for the treatment of depression or alcohol use disorder
  • Current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or Bipolar I or II Disorder
  • Current or history within one year of meeting DSM-5 criteria for a moderate or severe substance use disorder (excluding caffeine, nicotine, and alcohol)
  • If a smoker or nicotine user, consuming the equivalent of more than 10 cigarettes per day.
  • Have a first or second-degree relative with schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition)
  • Has a psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to psilocybin
  • History of a medically significant suicide attempt (e.g. an attempt characterized by strong intent and/or high lethality)
  • Has failed to respond to electroconvulsive therapy during the current major depressive episode
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alexandra R Tribo 410-550-2253 atribo1@jhmi.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04620759
Other Study ID Numbers  ICMJE IRB00233684
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Johns Hopkins University
Study Sponsor  ICMJE Johns Hopkins University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Frederick S Barrett, PhD Johns Hopkins University
PRS Account Johns Hopkins University
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP