Effect of Lithium Versus Placebo in Adults With Treatment-Resistant Depression Who Are Receiving Ketamine

NCT03290963 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 17-000819
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to compare the antidepressant effect of lithium versus placebo in adults receiving ketamine. Lithium is available commercially for depression; ketamine is available commercially and can help the symptoms of depression; however, it has not been approved by the U.S. Food and Drug Administration (FDA) for this use. The FDA has allowed the use of this drug in this research study.

Conditions

Treatment Resistant Depression

Keywords

depression; bipolar I disorder; bipolar II disorder

Outcome Measures

Primary Outcomes (2)

• Change in Montgomery-Asberg Depression Rating Scale (MADRS)

  The Montgomery Asberg Depression Scale (MADRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed).

  baseline, at the end of the first infusion (approximately 1 day)

• Change in Montgomery-Asberg Depression Rating Scale (MADRS)

  The Montgomery Asberg Depression Scale (MADRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed).

  baseline, at the end of third infusion (approximately 7 days)

Study Arms (2)

Ketamine plus Lithium

ACTIVE COMPARATOR

Lithium will be used in conjunction to Ketamine infusions for the treatment of major depression disorder or bipolar disorder type I or II. Before the first ketamine infusion, subjects will be randomized to 2 weeks of lithium treatment. All subjects will receive three IV ketamine infusions (0.5 mg/kg, over 100 min.) over 7 days. Those who achieve positive response (\>50% decrease in MADRS total score from baseline) will be given 4 additional once-weekly ketamine infusions (same dose and infusion rate) and lithium treatment .

Drug: Lithium; Drug: Ketamine

Ketamine plus Placebo

PLACEBO COMPARATOR

Placebo tablets will be used in conjunction to Ketamine infusions for the treatment of major depression disorder or bipolar disorder type I or II. Before the first ketamine infusion, subjects will be randomized to 2 weeks of placebo treatment. All subjects will receive three IV ketamine infusions (0.5 mg/kg, over 100 min.) over 7 days. Those who achieve positive response (\>50% decrease in MADRS total score from baseline) will be given 4 additional once-weekly ketamine infusions (same dose and infusion rate) and placebo treatment.

Drug: Placebo; Drug: Ketamine

Interventions

Lithium DRUG

Lithium will be dosed in units (LI level \> or = 0.4 milliequivalents (mEq)/L)

Also known as: Lithane, Lithobid

Ketamine plus Lithium

Placebo DRUG

Placebo tablets, dosed in units

Ketamine plus Placebo

Ketamine DRUG

All subjects will receive 3 IV ketamine infusions of 0.5mg/kg, over 100 min. over 7 days.

Also known as: Ketalar

Ketamine plus Lithium; Ketamine plus Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Ability to provide informed consent;
• Current psychiatric inpatient (voluntary only) or outpatient treatment;
• Meets Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) diagnostic criteria for major depressive disorder, bipolar I disorder, or bipolar II disorder;
• item Patient Health Questionnaire (PHQ-9) total score \> 15 at screening and at baseline (just prior to first acute phase ketamine infusion);
• Treatment-resistant depression, as defined by failure of at least two previous antidepressant or mood stabilizing treatments within the current depressive episode. Failed antidepressant or mood stabilizing treatments can include pharmacotherapy for depression at an adequate dose for at least 8 weeks, or an acute series of at least 6 administrations of electroconvulsive therapy (ECT);
• Adequate social support, defined as having at least one individual identified who is committed to function as support, including providing transportation to and from outpatient ketamine infusion visits;
• Ability to pass a comprehension assessment test related to effects of ketamine and trial objectives and criteria.

You may not qualify if:

• Diagnosis of schizophrenia, schizoaffective disorder, or active psychotic symptoms;
• On active lithium treatment;
• Serious risk for suicide, as assessed by the evaluating study clinician; a serious suicide risk will be considered: (a) an inability to control suicide impulses or imminent or unacceptably high risk of suicide in the investigator's judgment; or (b) a recent history of suicidal behavior, which is defined as either one or more suicide attempts (or interrupted suicide attempts) in the 12 months before study entry; or (c) history of serious suicidal behavior, defined as one or more suicide attempts (or interrupted attempts) in the last 3 years with a potential lethality judged by the evaluating study clinician to have possibly resulted in serious injury or death;
• Ongoing prescription of \> 4 mg lorazepam equivalents (total) daily, or morning dosing of any benzodiazepine at the time of assessment;
• Currently undergoing ECT, transcranial magnetic stimulation, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression;
• Use or abuse of methamphetamine, cocaine, cannabis, or stimulants (prescribed and illicit) within the past 12 months;
• Any current abuse or dependence of alcohol or drugs (excluding nicotine and caffeine). Note: Persons will be allowed to enroll in this study if their drug or alcohol abuse/dependence is in complete (not partial) and sustained (\> 1 year) remission;
• History of traumatic brain injury that resulted in loss of consciousness;
• Developmental delay, mental retardation, or intellectual disorder;
• Clinical or self-reported diagnosis of delirium, encephalopathy, or related clinical diagnosis within the prior 12 months;
• Cognitive disorder (mild and major categories, per DSM-5);
• Prior participation in another study of ketamine for depression within the prior 6 months;
• History of either poor antidepressive response to or poor tolerability of ketamine (any route of administration) when previously administered for treating symptoms of depression;
• History of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic for 6 months;
• Significant unstable medical condition

Sponsors & Collaborators

• William V. Bobo, M.D.: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression; Bipolar Disorder

Interventions

Lithium; Lithium Carbonate; Ketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Bipolar and Related Disorders

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals; Carbonates; Alkalies; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• William V Bobo

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Triple blinded study. The staff accessible to the blind includes pharmacy staff and one assigned investigator.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: September 25, 2017
• Study Start: November 30, 2017
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: August 16, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)