A Study to Investigate Evoked Potentials as Markers of Ketamine-induced Cortical Plasticity in Patients With Major Depressive Disorder

NCT ID: NCT01957410

Last Updated: 2017-01-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2015-09-30

Brief Summary

To evaluate if somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) obtained with electroencephalography (EEG) and electromyography (EMG) can be used to detect changes in cortical plasticity in responders to a single IV infusion of ketamine as compared to non-responders.

Detailed Description

This study will be conducted in patients with Major Depressive Disorder (MDD) and divided into 2 sequential cohorts. Cohort 1 will be conducted in 12 patients at a single center. For each patient, there will be up to 4 sequential phases: a screening phase of up to 6 weeks, an open-label treatment phase of up to 4 weeks, an optional open-label treatment phase of up to 1 week, and a follow-up phase of up to 1 week (if applicable). Cohort 2 will be conducted in 20 patients and will be a multicenter, double-blind (neither physician nor patient knows the treatment that the patient receives), randomized (the study drug is assigned by chance), placebo-controlled (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial) design. For each patient, there will be up to 4 sequential phases: a screening phase of up to 6 weeks, a double-blind treatment phase of up to 4 weeks, an optional open-label treatment phase of up to 1 week, and a follow-up phase of up to 1 week (if applicable). The total study duration for each patient will be maximally about 12 weeks. Participant safety will be monitored throughout the study.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Ketamine Intravenous (IV)

Patients will receive a single IV dose of ketamine given as a continuous infusion.

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

During Cohorts 1 and 2, a single ketamine 0.5 mg/kg dose will be given as a continuous IV infusion over 40 minutes by use of an electronic syringe infusion pump. The predefined dose and infusion rate/duration should not be adjusted. If a patient is unable to tolerate the study medication, the infusion should be stopped. Within 1 week of completion of the open-label treatment phase, participants can receive a single dose of ketamine 0.5 mg/kg administered as an IV infusion over 40 minutes during an optional open-label treatment phase.

Placebo Intravenous (IV)

Patients will receive a single IV dose of placebo given as a continuous infusion.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

During Cohort 2, a single placebo dose will be given as a continuous IV infusion over 40 minutes by use of an electronic syringe infusion pump. Within 1 week of completion of the double-blind treatment phase, participants can receive a single dose of ketamine 0.5 mg/kg administered as an IV infusion over 40 minutes during an optional open-label treatment phase.

Interventions

Ketamine

During Cohorts 1 and 2, a single ketamine 0.5 mg/kg dose will be given as a continuous IV infusion over 40 minutes by use of an electronic syringe infusion pump. The predefined dose and infusion rate/duration should not be adjusted. If a patient is unable to tolerate the study medication, the infusion should be stopped. Within 1 week of completion of the open-label treatment phase, participants can receive a single dose of ketamine 0.5 mg/kg administered as an IV infusion over 40 minutes during an optional open-label treatment phase.

Intervention Type: DRUG

Placebo

During Cohort 2, a single placebo dose will be given as a continuous IV infusion over 40 minutes by use of an electronic syringe infusion pump. Within 1 week of completion of the double-blind treatment phase, participants can receive a single dose of ketamine 0.5 mg/kg administered as an IV infusion over 40 minutes during an optional open-label treatment phase.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patient must be medically stable
• Patient must meet Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) diagnostic criteria for Major Depressive Disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the Mini International Psychiatric Interview (MINI)
• Patient must have had an inadequate response to at least 2 antidepressants, one of which is in the current episode of depression
• Patient must have an Inventory of Depressive Symptomatology 30-item Clinician-rated (IDS-C30) total score ≥ 34 at Screening and Day -1
• Women must be postmenopausal, surgically sterile, or, if heterosexually active, practicing a highly effective method of birth control
• Men who are heterosexually active with a woman of childbearing potential must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug

Exclusion Criteria

• Patient has current signs and/or symptoms of liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbances
• Patient has a primary DSM-IV diagnosis of current (active) generalized anxiety disorder (GAD), panic disorder, obsessive compulsive disorder (OCD), posttraumatic stress disorder (PTSD), anorexia nervosa, or bulimia nervosa
• Patient has a current diagnosis of bipolar disorder, mental retardation, or cluster b personality disorder (e.g., borderline personality disorders, antisocial personality disorder, etc)
• Patient has a current or prior diagnosis of a psychotic disorder or MDD with psychosis
• Patient has not responded to treatment with electroconvulsive therapy (ECT) in the current episode of depression
• Patient has suicidal ideation with intent to act, or has homicidal ideation/intent, during Screening phase per Investigator's clinical judgment
• Patient has any significant primary sleep disorder

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Durham, North Carolina, United States

Countries

United States

Other Identifiers

KETIVTRD2004

Identifier Type: OTHER

Identifier Source: secondary_id

CR102607

Identifier Type: -

Identifier Source: org_study_id