Opiate Suicide Study in Patients With Major Depression

Recruiting

I'm Interested

Trial ID: NCT04116528

Purpose

To explore whether intravenous ketamine followed by buprenorphine produces more rapid and sustained anti-suicidal effects than ketamine followed by placebo, investigators will conduct a single study that will take approximately 2.5 years to complete. 60 subjects (60 infusions) or approximately 24 infusions per year.

Official Title

Opiate Suicide Study in Patients With Major Depression

Stanford Investigator(s)

Ian H. Kratter, MD, PhD
Ian H. Kratter, MD, PhD

Clinical Assistant Professor, Psychiatry and Behavioral Sciences

Jason Tucciarone, MD, PhD

Assistant Professor of Psychiatry and Behavioral Sciences (General Psychiatry and Psychology)

Alan F. Schatzberg
Alan F. Schatzberg

Kenneth T. Norris, Jr. Professor of Psychiatry and Behavioral Sciences

Eligibility


Inclusion Criteria:

   - A subject will be eligible for inclusion only if all of the following criteria are
   met:

      1. Male or female, 18 to 70 years of age, inclusive, at screen.

      2. Able to read, understand, and provide written, dated informed consent prior to
      screening. Participants will be deemed likely to comply with study protocol and
      communicate with study personnel about adverse events and other clinically
      important information.

      3. Diagnosed with Major Depressive Disorder (MDD), single or recurrent or Bipolar-II
      Disorder and currently experiencing a Major Depressive Episode (MDE) of at least
      eight weeks in duration, prior to screening, according to the criteria defined in
      the Diagnosis and Statistical Manual of Mental Disorders, Fourth Edition, Text
      Revision(DSM-IV-TR™). The diagnosis of MDD will be made by a site psychiatrist
      and supported by the Structured Clinical Interview for DSM-IV-TR™ (SCID-I/P).

      4. Has a history of TRD during the current MDE, as assessed by the investigator. TRD
      is defined as failure to achieve a satisfactory response (e.g., less than 50%
      improvement of depression symptoms), as perceived by the participant, to at least
      one "treatment course" of a therapeutic dose of an antidepressant therapy of at
      least 8 weeks duration. The adequacy of dose and duration of the antidepressant
      therapy will be determined as per the MGH ATRQ criteria. Participants must
      currently be on a stable (for at least 4 weeks) and adequate (according to the
      MGH ATRQ) dose of ongoing SSRI or SNRI antidepressant therapy, of which total
      duration must be at least 8 weeks. Participants may also have a history of
      intolerance to at least 2 antidepressant medications. These patients with the
      intolerance history will not be required to be currently taking an antidepressant
      medication.

      5. Meet the threshold on the total SSI score of >/=6 at both screening and baseline
      visits.

      6. Participants must qualify as "Moderately Treatment Refractory" using the Maudsley
      staging method, which incorporates past treatments, severity of symptoms and
      duration of presenting episode.

      7. In good general health, as ascertained by medical history, physical examination
      (PE) (including measurement of supine and standing vital signs), clinical
      laboratory evaluations, and 3-lead electrocardiogram (ECG) if no evaluation
      available from the last 6 months.

      8. If female, a status of non-childbearing potential or use of an acceptable form of
      birth control per the following specific criteria:

      a. Non-childbearing potential (e.g., physiologically incapable of becoming
      pregnant, i.e., permanently sterilized (status post hysterectomy, bilateral tubal
      ligation), or is post-menopausal with her last menses at least one year prior to
      screening); or b. Childbearing potential, and meets the following criteria: i.
      Childbearing potential, including women using any form of hormonal birth control,
      on hormone replacement therapy started prior to 12 months of amenorrhea, using an
      intrauterine device (IUD), having a monogamous relationship with a partner who
      has had a vasectomy, or is sexually abstinent.

      ii. Negative urinary pregnancy test at screening, confirmed by a negative urinary
      pregnancy test at randomization prior to receiving study treatment.

      iii. Willing and able to continuously use one of the following methods of birth
      control during the course of the study, defined as those which result in a low
      failure rate (i.e., less than 1% per year) when used consistently and correctly:
      implants, injectable or patch hormonal contraception, oral contraceptives, IUD,
      double-barrier contraception, sexual abstinence. The form of birth control will
      be documented at screening and baseline.

      9. Body mass index between 17-40kg/m2.

   10. Concurrent psychotherapy will be allowed if the type (e.g., supportive, cognitive
      behavioral, insight-oriented, et al) and frequency (e.g., weekly or monthly) of
      the therapy has been stable for at least three months prior to screening and if
      the type and frequency of the therapy is expected to remain stable during the
      course of the subject's participation in the study.

   11. Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, or
      trazodone) will be allowed if the therapy has been stable for at least 4 weeks
      prior to screening and if it is expected to remain stable during the course of
      the subject's participation in the study.

      Exclusion Criteria:

   - A potential participant will NOT be eligible for participation in this study if any of
   the following criteria are met:

      1. Female of childbearing potential who is not willing to use one of the specified
      forms of birth control during the study.

      2. Female that is pregnant or breastfeeding.

      3. Female with a positive pregnancy test at screening or baseline.

      4. Total SSI score of <6 at the screen or baseline visits.

   6. Current diagnosis of a Substance Use Disorder (Abuse or Dependence, as defined by
   DSM-IV-TR™), with the exception of nicotine dependence, at screening or within six
   months prior to screening.

   7. Current diagnosis of Axis I disorders other than Dysthymic Disorder, Generalized
   Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, or Specific
   Phobia (unless one of these is comorbid and clinically unstable, and/or the focus of
   the participant's treatment for the past six months or more).

   8. History of schizophrenia or schizoaffective disorders, or any history of psychotic
   symptoms in the current or previous depressive episodes.

   9. History of anorexia nervosa, bulimia nervosa, or eating disorder not otherwise
   specified, within one year of screening.

   10. Any Axis I or Axis II Disorder, which at screening is clinically predominant to
   their MDD or has been predominant to their MDD at any time within six months prior to
   screening. A diagnosis of borderline personality disorder is excluded.

   11. In the judgment of the investigator, the subject is at significant risk for
   suicidal behavior during the course of his/her participation in the study.

   12. Has dementia, delirium, amnestic, or any other cognitive disorder.

   13. Has a clinically significant abnormality on the screening physical examination
   that might affect safety, study participation, or confound interpretation of study
   results.

   14. Participation in any clinical trial with an investigational drug or device within
   the past month or concurrent to study participation.

   15. Known history or current episode of:

      1. QTcF (Fridericia-corrected) ≥450 msec at screening (Visit 1) or randomization

      2. Syncopal event within the past year.

      3. Congestive heart failure (CHF) New York Heart Association Criteria >Stage 2

      4. Angina pectoris

      5. Heart rate <50 or >105 beats per minute at screening or randomization

      16. Chronic lung disease.

      17. Lifetime history of surgical procedures involving the brain or meninges,
      encephalitis, meningitis, degenerative central nervous system disorder (e.g.,
      Alzheimer's or Parkinson's Disease), epilepsy, mental retardation, or any other
      disease/procedure/accident/intervention associated with significant injury to or
      malfunction of the central nervous system (CNS), or a history of significant head
      trauma within the past two years.

      18. Presents with any of the following lab abnormalities w/in the past 6 months:

      1. Thyroid stimulating hormone (TSH) outside of the normal limits and clinically
      significant as determined by the investigator. Free thyroxine (T4) levels may be
      measured if TSH level is high. Subject will be excluded if T4 level is clinically
      significant.

      2. Any other clinically significant abnormal laboratory result at the time of the
      screening exam.

      19. History of hypothyroidism and has been on a stable dosage of thyroid
      replacement medication for less than six months prior to screening.(Subjects on a
      stable dosage of thyroid replacement medication for at least six months or more
      prior to screening are eligible for enrollment.)

      20. History of hyperthyroidism which was treated (medically or surgically) less
      than six months prior to screening.

      21. Any current or past history of any physical condition which in the
      investigator's opinion might put the subject at risk or interfere with study
      results interpretation.

      22. History of positive screening urine test for drugs of abuse at screening:
      cocaine, amphetamines, barbiturates, opiates.

      23. Current (or chronic) use of opiates. History of Opioid Use Disorder.

      24. Current use of lamotrigine and an inability to stop the medication prior to
      receiving ketamine.

Intervention(s):

drug: Ketamine

drug: Buprenorphine

drug: Placebo oral tablet

Recruiting

I'm Interested

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Jessica Hawkins
650-723-8323