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

Primary Purpose

Major Depressive Disorder

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Ketamine

Placebo

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring Major Depressive Disorder, Ketamine, Evoked potentials, Somatosensory evoked potentials, Motor evoked potentials, Cortical plasticity

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ketamine Intravenous (IV)

Placebo Intravenous (IV)

Arm Description

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

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

Outcomes

Primary Outcome Measures

Comparison of Ketamine Responders and Ketamine Non-responders in the Change From Baseline in Somatosensory Evoked Potential (SEPs) Amplitudes at 4 Hours Postdose on Day 1

SEPs are the electrical signals generated by the nervous system in response to somatosensory stimuli - typically through electrical stimulation of the median nerve. SEPs are read on the skull with electroencephalography (EEG). SEPs was recorded using a 64-channel EEG system at baseline (predose) and regularly after study drug administration. The change from baseline was calculated as post-baseline value minus baseline value for each participant. Since the number of participants at baseline differ from the number of participants at post-baseline measure (that is [i.e.] not all baseline values are paired), the mean change is not equal to the difference between the means at the two time points.

Comparison of Ketamine Responders and Ketamine Non-responders in the Change From Baseline in Motor Evoked Potential (MEPs) Amplitudes at 4 Hours Postdose on Day 1

MEPs are generated when stimulation of the brain on the motor cortex (with Transcranial Magnetic Stimulation [TMS]) causes the spinal cord and peripheral muscles to produce neuroelectrical signals. MEPs are typically measured in the hand muscles. The Motor Evoked Response to Transcranial Magnetic Stimulation (TMS MEPs) was evaluated at baseline and regularly after study drug administration. Intracortical inhibition and facilitation was also evaluated using TMS. A figure-of-eight coil with external loop diameters of 9 cm was used to elicit motor responses in the contralateral first dorsal interosseus.

Secondary Outcome Measures

Full Information

NCT ID

NCT01957410

First Posted

September 30, 2013

Last Updated

December 5, 2016

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT01957410

Brief Title

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

Official Title

An Open-Label and Double-Blind Study to Investigate Evoked Potentials as Markers of Ketamine-induced Cortical Plasticity in Subjects With Major Depressive Disorder

Study Type

Interventional

2. Study Status

Record Verification Date

December 2016

Overall Recruitment Status

Terminated

Why Stopped

Clinical Team decision to terminate the study after the results from Cohort 1 did not support conducting Cohort 2.

Study Start Date

February 2014 (undefined)

Primary Completion Date

September 2015 (Actual)

Study Completion Date

September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Major Depressive Disorder

Keywords

Major Depressive Disorder, Ketamine, Evoked potentials, Somatosensory evoked potentials, Motor evoked potentials, Cortical plasticity

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ketamine Intravenous (IV)

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo Intravenous (IV)

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Ketamine

Intervention Description

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

Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

Comparison of Ketamine Responders and Ketamine Non-responders in the Change From Baseline in Somatosensory Evoked Potential (SEPs) Amplitudes at 4 Hours Postdose on Day 1

Description

Time Frame

Baseline and Day 1 (4 hours postdose)

Title

Comparison of Ketamine Responders and Ketamine Non-responders in the Change From Baseline in Motor Evoked Potential (MEPs) Amplitudes at 4 Hours Postdose on Day 1

Description

Time Frame

Baseline and Day 1 (4 hours postdose)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Research & Development, LLC Clinical Trial

Organizational Affiliation

Janssen Research & Development, LLC

Official's Role

Study Director

Facility Information:

City

Durham

State/Province

North Carolina

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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