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Ketamine Plus Lithium in Treatment-Resistant Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01880593
Recruitment Status : Completed
First Posted : June 19, 2013
Results First Posted : July 31, 2018
Last Update Posted : July 31, 2018
Sponsor:
Information provided by (Responsible Party):
James Murrough, Icahn School of Medicine at Mount Sinai

Tracking Information
First Submitted Date  ICMJE June 14, 2013
First Posted Date  ICMJE June 19, 2013
Results First Submitted Date  ICMJE January 8, 2018
Results First Posted Date  ICMJE July 31, 2018
Last Update Posted Date July 31, 2018
Study Start Date  ICMJE July 2013
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 5, 2018)
MADRS-S Score [ Time Frame: 2 weeks after last ketamine infusion ]
The Montgomery Asberg Depression Rating Scale (MADRS-S) has 10-items which are based on mood symptoms over the past 7 days. Each items is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression).
Original Primary Outcome Measures  ICMJE
 (submitted: June 14, 2013)
Montgomery Asberg Depression Rating Scale [ Time Frame: 2 weeks after last ketamine infusion ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 5, 2018)
  • QIDS-SR Score [ Time Frame: 2 weeks after last ketamine infusion ]
    Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR) score - Each item is rated 0 (no depression) to 3 (severe depression), for a total score range of 0 (no depression) to 27 (severe depression).
  • CGI-S Score [ Time Frame: 2 weeks after last ketamine infusion ]
    The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
  • HAM-A Score [ Time Frame: 2 weeks after last ketamine infusion ]
    Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
  • BSS Score [ Time Frame: 2 weeks after last ketamine infusion ]
    BECK Scale for Suicidal Ideation (BSS) - 0-13 Minimal; 14-19 Mild; 20-28 Moderate; 29-63 Severe
  • CSSRS Score [ Time Frame: 2 weeks after last ketamine infusion ]
    Columbia Suicide Severity Rating Scale (CSSRS) - Full range from 0 (low intensity suicidal ideation to 9 (high intensity suicidal ideation).
  • Patient Rated Inventory of Side Effects (PRISE) [ Time Frame: 2 weeks after last ketamine infusion ]
    Number of Participants with PRISE
Original Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2013)
  • Quick Inventory of Depressive Symptoms [ Time Frame: 2 weeks after last ketamine infusion ]
  • Patient Rated Inventory of Side Effects (PRISE) [ Time Frame: at 2 weeks ]
  • Clinical Global Impression [ Time Frame: at 2 weeks ]
  • Hamilton Psychiatric Rating Scale for Anxiety (HAM-A) [ Time Frame: at 2 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine Plus Lithium in Treatment-Resistant Depression
Official Title  ICMJE Ketamine Plus Lithium as a Novel Pharmacotherapeutic Strategy in Treatment-Resistant Depression
Brief Summary

The purpose of this study is to test the antidepressant effect of ketamine when given repeatedly over a period of 1 week, as well as the use of Lithium as a relapse-prevention strategy for patients with treatment-resistant depression (TRD) who respond to an initial series of ketamine infusions. Ketamine is a Food and Drug Administration approved anesthetic (a drug used to produce loss of consciousness before and during surgery). Ketamine is not approved for the treatment of major depressive disorder and is considered experimental in this study. An additional purpose of this study is to research the effects of ketamine on brain function.

You may qualify to take part in this research study because you have been diagnosed with major depressive disorder (MDD) and have not responded to past treatments.

Detailed Description Major Depressive Disorder (MDD) is a disabling medical illness and current monoaminergic treatments are slow to act and possess only limited efficacy. In this context, the discovery that the glutamate NMDA receptor antagonist ketamine is rapidly antidepressant (onset of action within hours) -- even in patients suffering from treatment-resistant depression (TRD) -- has ignited tremendous enthusiasm among clinicians, scientists and patients alike. A critical obstacle to the translation of this discovery into a novel treatment, however, is the limited duration of action following a course of ketamine (e.g. 1-2 weeks). The current project will address this important gap in medical knowledge by testing a rational neuropharmacological strategy designed to optimize and sustain the rapid antidepressant effects of ketamine. Driven by the recent characterization of the molecular mechanisms underpinning the antidepressant and neuroplasticity effects of ketamine, we will test the combination of ketamine plus lithium in patients with TRD using a randomized, double blind, placebo-controlled design. The primary aims of the project are (1) to test the efficacy of lithium-plus-ketamine compared to placebo-plus-ketamine as an antidepressant combination strategy in TRD and (2) to gather data on the safety and tolerability of the lithium-plus-ketamine.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Depression
Intervention  ICMJE
  • Drug: Lithium
    Subjects in this arm take 600-1200mg of Lithium pills at night for duration of the study.
    Other Name: Lithium Carbonate Immediate Release
  • Drug: Ketamine
  • Drug: Placebo
    Subjects in this arm take placebo pills at night for duration of the study.
Study Arms  ICMJE
  • Experimental: Ketamine and Lithium
    Subjects in this arm take 600-1200mg of Lithium pills at night for duration of the study
    Interventions:
    • Drug: Lithium
    • Drug: Ketamine
  • Placebo Comparator: Ketamine and Placebo
    Subjects in this arm take placebo pills at night for duration of the study.
    Interventions:
    • Drug: Ketamine
    • Drug: Placebo
Publications * Murrough JW, Perez AM, Pillemer S, Stern J, Parides MK, aan het Rot M, Collins KA, Mathew SJ, Charney DS, Iosifescu DV. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry. 2013 Aug 15;74(4):250-6. doi: 10.1016/j.biopsych.2012.06.022. Epub 2012 Jul 27.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: July 5, 2018)
34
Original Estimated Enrollment  ICMJE
 (submitted: June 14, 2013)
45
Actual Study Completion Date  ICMJE November 2016
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female patients, 21-65 years of age;
  • Female individuals who are not of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year) or using a medically accepted reliable means of contraception. Women using oral contraceptive medication for birth control must also be using a barrier contraceptive. Women of childbearing potential must also have a negative serum B-HCG at screening and at pre-infusion;
  • Participants must fulfill DSM-IV criteria for Major Depression without psychotic features, based on clinical assessment by a study psychiatrist and confirmed by a structured diagnostic interview, the Structured Clinical Interview for DSM-IV TR Axis I Disorders, Patient Edition (SCID-P);
  • Participants must have a history of at least one previous episode of depression prior to the current episode (recurrent MDD) or have chronic MDD (of at least two years' duration);
  • Participants have not responded to two or more adequate trials of an antidepressant as determined by Antidepressant Treatment History Form (ATHF) criteria (score >=3);
  • Current Major Depressive Episode of at least moderate severity, defined as a QIDS-SR score ≥ 14 and a CGI-S score of ≥ 4;Current major depressive episode is of at least 4 weeks duration;
  • Each participant must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document;
  • Each participant must be able to identify a family member, physician, or friend who will participate in the Treatment Contract.

Exclusion Criteria:

  • Lifetime history of psychotic features, diagnosis of schizophrenia or any other psychotic disorder, or diagnosis of bipolar disorder;
  • Lifetime histories of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome;
  • Current diagnosis of OCD or eating disorder (bulimia nervosa or anorexia nervosa);
  • Subjects with DSM-IV drug or alcohol abuse/dependence within the preceding 2 years;
  • Patients with schizotypal or antisocial personality disorder, or any clinically significant axis II disorder that would, in the investigator's judgment, preclude safe study participation;
  • Patients judged clinically to be at serious and imminent suicidal or homicidal risk;
  • Women who are either pregnant or nursing;
  • Serious, unstable medical illnesses including hepatic, renal impairment, gastroenterologic (including gastro-esophageal reflux disease), respiratory (including obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics), cardiovascular (including ischemic heart disease and uncontrolled hypertension), endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
  • Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
  • Patients who have a positive urine toxicology for illicit substances at screening and within 24 hours of the infusion;
  • Patients with one or more seizures without a clear and resolved etiology;
  • Treatment with an irreversible MAOI within 2 weeks prior to randomization or fluoxetine within 4 weeks prior to randomization;
  • Treatment with other antidepressants within one week of randomization;
  • Previous recreational use of PCP or ketamine;
  • Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg) not controlled by diuretic or beta-blocker therapy alone or in combination;
  • A blood pressure reading over 160/90 or two separate readings over 140/90 at screening or baseline visits;
  • Renal impairment, as reflected by a BUN > 20 mg/dL and/or creatinin clearance of >1.3 mg/dL;
  • Thyroid impairment, as reflected by a TSH > 4.2 mU/L;
  • Cardiac disease, as reflected by an EKG that is abnormal and of concern for cardiac disease;
  • Any anticipated change in medications that could affect fluid or salt balance, including the following antihypertensive agents: ACE inhibitor, loop diuretics, calcium channel blockers, thiazide diuretics, angiotensin II receptor blockers.
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01880593
Other Study ID Numbers  ICMJE GCO 13-0365
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party James Murrough, Icahn School of Medicine at Mount Sinai
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Icahn School of Medicine at Mount Sinai
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: James W Murrough, MD Icahn School of Medicine at Mount Sinai
PRS Account Icahn School of Medicine at Mount Sinai
Verification Date July 2018

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