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Double-Blind, Placebo-Controlled Trial of Ketamine Therapy in Treatment-Resistant Depression (TRD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by Massachusetts General Hospital
Sponsor:
Collaborators:
National Institute of Mental Health (NIMH)
Baylor College of Medicine
Icahn School of Medicine at Mount Sinai
Stanford University
University of Texas
Yale University
Information provided by (Responsible Party):
Maurizio Fava, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01920555
First received: August 8, 2013
Last updated: May 26, 2016
Last verified: May 2016
  Purpose
This study is looking at the efficacy, durability, safety, and tolerability of multiple single doses of Ketamine vs. active placebo for treating patients with treatment resistant depression who are taking an antidepressant that is not working for them.

Condition Intervention Phase
Treatment Resistant Depression
Drug: Ketamine
Drug: Placebo Midazolam
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-Blind, Placebo-Controlled Trial of Ketamine Therapy in Treatment-Resistant Depression (TRD)

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Hamilton Rating Scale for Depression - 6 items [ Time Frame: Past 24 hours ] [ Designated as safety issue: No ]
    This instrument is completed with a structured interview guide by the clinician based on his/her assessment of the patient's symptoms. This structured interview has been validated for use with time frames shorter than one week. The time frame for this scale is the past 24 hours.


Estimated Enrollment: 100
Study Start Date: December 2014
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ketamine 0.1mg
Patients in this arm will receive 0.1 mg/kg of Ketamine - one single infusion
Drug: Ketamine
Dose of Ketamine will be 0.1 mg/kg - one single infusion
Active Comparator: Ketamine 0.2mg
Patients in this arm will receive 0.2 mg/kg of Ketamine - one single infusion
Drug: Ketamine
Dose of Ketamine will be 0.2 mg/kg - one single infusion
Active Comparator: Ketamine 0.5mg
Patients in this arm will receive 0.5 mg/kg of Ketamine - one single infusion
Drug: Ketamine
Dose of Ketamine will be 0.5 mg/kg - one single infusion
Active Comparator: Ketamine 1.0mg
Patients in this arm will receive 1.0 mg/kg of Ketamine - one single infusion
Drug: Ketamine
Dose of Ketamine will be 1.0 mg/kg - one single infusion
Placebo Comparator: Midazolam (Active Placebo)
Patients in this arm will receive 0.045 mg/kg of midazolam - one single infusion
Drug: Placebo Midazolam
Dose of Midazolam (active placebo) will be 0.045 mg/kg - one single infusion

Detailed Description:
The primary objective is to investigate whether all doses (0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg, and 1.0 mg/kg) of ketamine are superior to active placebo (midazolam 0.045 mg/kg) therapy in the acute treatment of patients with treatment resistant depression within 72 hours (Day 3), when added to ongoing and stable antidepressant therapy.
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, 18-70 years old.
  • Able to read, understand, and provide written, dated informed consent prior to screening.
  • Diagnosed with Major Depressive Disorder (MDD), single or recurrent, and currently experiencing a Major Depressive Episode (MDE) of at least eight weeks in duration, prior to screening.
  • Has a history of TRD during the current MDE.
  • Meet the threshold on the total MADRS score of greater than or equal to 20 at both screening and baseline visits (Day -7/-28 and Day 0), as confirmed by the remote centralized MGH CTNI rater between the screen visit and the baseline visit.
  • In good general health
  • For female participants, status of non-childbearing potential or use of an acceptable form of birth control
  • Body mass index between 18-35 kg/m2
  • Concurrent psychotherapy will be allowed if the type and frequency of the therapy has been stable for at least three months prior to screening and is expected to remain stable during participation in the study
  • Concurrent hypnotic therapy 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:

  • Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study
  • Female that is pregnant or breastfeeding
  • Female with a positive pregnancy test at screening or baseline
  • History during the current MDE of failure to achieve a satisfactory response to >7 treatment courses of a therapeutic dose of an antidepressant therapy of at least 8 weeks duration during the current episode
  • Total MADRS score of <20 at the screen or baseline visits, or as assessed by the remote, independent MGH CTNI rater and reported to the site
  • Current diagnosis of a Substance Use Disorder (Abuse or Dependence) with the exception of nicotine dependence, at screening or within 6 months prior to screening
  • Current Axis I disorder that is the principal focus of treatment and MDD the secondary focus of treatment for the past 6 months or more
  • History of bipolar disorder, schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes
  • History of eating disorders within five years of screening
  • Any Axis I or Axis II Disorder, which at screening is clinically predominant to their MDD or has been predominant at any time within 6 months prior to screening
  • Subject is considered at significant risk for suicidal behavior during the course of their participation in the study
  • Has failed to respond to electroconvulsive therapy (ECT) during the current depressive episode
  • Has received vagus nerve stimulation (VNS) at any time prior to screening
  • Has dementia, delirium, amnestic, or any other cognitive disorder
  • Has a clinically significant abnormality on the screening physical examination
  • Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation
  • Current episode of:

    1. Hypertension, Stage 1 as defined by a systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90 mmHg at screening on two of three measurements (standing and supine) at least 15 minutes apart.
    2. Hypertension, Stage 1 as defined by a systolic blood pressure ≥155 mmHg or diastolic blood pressure ≥99 mmHg at the Baseline Visit (Visit 1) within 1.5 hours prior to randomization on two of three measurements (standing and supine) at least 15 minutes apart.
    3. Recent myocardial infarction (within one year) or a history of myocardial infarction.
    4. Syncopal event within the past year.
    5. Congestive heart failure (CHF) New York Heart Association Criteria >Stage 2
    6. Angina pectoris.
    7. Heart rate <50 or >105 beats per minute at screening or randomization (Baseline Visit).
    8. QTcF (Fridericia-corrected) ≥450 msec at screening or randomization (Baseline Visit).
  • Current history of hypertension, or on antihypertensives for the purpose of lowering blood pressure, who have either had an increase in antihypertensive dose or increase in the number of antihypertensive drugs used to treat hypertension over the last 2 months.
  • Chronic lung disease excluding asthma.
  • Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system disorder, epilepsy, mental retardation, or any other disease/procedure/accident/intervention associated with significant injury to or malfunction of the central nervous system, or a history of significant head trauma within the past 2 years
  • Presents with any of the following lab abnormalities:

    1. Thyroid stimulating hormone 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. Patients with diabetes mellitus fulfilling any of the following criteria:

    i. Unstable diabetes mellitus defined as glycosylated hemoglobin (HbA1c) >8.5% at screening ii. Admitted to hospital for treatment of diabetes mellitus or diabetes mellitus related illness in the past 12 weeks iii. Not under physician care for diabetes mellitus iv. Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to screening. For thiazolidinediones (glitazones) this period should not be less than 8 weeks.

    c. Any other clinically significant abnormal laboratory result (as determined after evaluation by study investigator and MGH CTNI medical monitor) at the time of the screening exam.

  • History of hypothyroidism and has been on a stable dosage of thyroid replacement medication for less than 2 months prior to screening. (Subjects on a stable dosage of thyroid replacement medication for at least 2 months or more prior to screening are eligible for enrollment.)
  • History of hyperthyroidism which was treated (medically or surgically) less than six months prior to screening
  • 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
  • History of positive screening urine test for drugs of abuse at screening
  • Patients with exclusionary laboratory values, or requiring treatment with exclusionary concomitant medications
  • Patients on exclusionary concomitant psychotropic medications, the half-life of which would not allow sufficient time for patients to have been free of the medication post-taper for five half-lives within the maximum screening period (28 days).
  • Patient who have participated in studies of ketamine or AZD6765 or other NMDA receptor antagonists for depression and received active treatment.
  • Patients with narrow angle glaucoma
  • Patients with a lifetime history of PCP/Ketamine drug use
  • Liver Function Tests higher than 2.5 times upper limit of normal
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01920555

Contacts
Contact: Yury Montas ymontas@partners.org

Locations
United States, California
Stanford University Recruiting
Palo Alto, California, United States, 94304
Contact: Jessica Hawkins    650-723-8323    jhawk@stanford.edu   
Principal Investigator: Charles DeBattista, MD         
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06520
Contact: Jane Wanyiri    203-764-9131    jane.wanyiri@yale.edu   
Principal Investigator: Gerard Sanacora, MD, PhD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Abby Archibald    617-724-3222    aarchibald@partners.org   
Principal Investigator: Cristina Cusin, MD         
Sub-Investigator: Dawn Ionescu, MD         
United States, New York
Mount Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Contact: Jackie Schwartz    212-241-3116    jaclyn.schwartz@mssm.edu   
Principal Investigator: Dan V Iosifescu, MD         
United States, Texas
University of Texas Southwestern Recruiting
Dallas, Texas, United States, 75390
Contact: Maria Monastirsky    214-648-0174    Maria.Monastirsky@UTSouthwestern.edu   
Principal Investigator: Madhukar Trivedi, MD         
Sub-Investigator: Marisa Toups, MD         
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Lorna Hirsch    713-689-9856    mood@bcm.edu   
Principal Investigator: Sanjay J Mathew, MD         
Sponsors and Collaborators
Massachusetts General Hospital
National Institute of Mental Health (NIMH)
Baylor College of Medicine
Icahn School of Medicine at Mount Sinai
Stanford University
University of Texas
Yale University
Investigators
Principal Investigator: Maurizio Fava, MD Massachusetts General Hospital
  More Information

Responsible Party: Maurizio Fava, MD, Overall Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01920555     History of Changes
Other Study ID Numbers: RAP-003  271201100006I-0-27100007-1 
Study First Received: August 8, 2013
Last Updated: May 26, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Keywords provided by Massachusetts General Hospital:
Depression
Treatment Resistant Depression
Ketamine
Antidepressant
MDD
Major Depression

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders
Ketamine
Midazolam
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adjuvants, Anesthesia
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents

ClinicalTrials.gov processed this record on December 05, 2016