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The Effect of Minocycline on Relapse After Successful Intravenous Ketamine/Minocycline-induced Symptoms Response in Subjects With Depression

Primary Purpose

Depressive Disorder

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Minocycline

Placebo

Ketamine

About this trial

This is an interventional treatment trial for Depressive Disorder focused on measuring Depressive Disorder, Major Depressive Disorder, Depression, Bipolar Disorder Type II, Anti-depressant, Ketamine, Minocycline

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnostic criteria for moderate to severe major depressive disorder (MDD), without psychotic features, or Bipolar Disorder Type II
Patients should have an Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) total score ≥ 34 at Screening and at Day 1 (predose)
Patients with major depressive disorder should have failed at least two adequate treatment courses (dose and duration) with antidepressant therapy, one of which is in the current episode
Patients should not have received electroconvulsive therapy (ECT) in the current episode but could be those for whom ECT is considered
Patients with bipolar depression (BPD) Type II must have been taking a stable dose of a mood-stabilizing medication (e.g., lithium, valproate, carbamazepine, lamotrigine, antipsychotic agents) for at least 4 weeks, dosed clinically to target the therapeutic range
Patients currently taking an antidepressant(s) must have received at least 2 weeks of stable antidepressant therapy at the time of Screening
Doses of current antidepressant therapies should remain the same for the duration of the study
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:

Has a current DSM-IV axis I diagnosis other than MDD or BPD Type II at screening (except for co-morbid anxiety disorders)
Has a diagnosis of substance abuse or dependence within 6 months prior to screening evaluation (nicotine and caffeine dependence are not exclusionary)
Patient is currently taking more than 4 psychotropic medications at Day 1 (predose)
Has an autoimmune disorder such as Crohn's disease, rheumatoid arthritis, psoriasis currently treated with/requiring treatment with immunomodulatory therapies
Has any significant cardiovascular, respiratory, neurologic, renal, hepatic, endocrine, or immunologic diseases based on screening examination
Has uncontrolled hypertension (diastolic blood pressure ≥ 90 mmHg), despite diet, exercise or a stable dose of an allowed antihypertensive treatment, at Screening or Day 1 (predose)
Has planned vaccination within 2 weeks prior to the first dose of study medication through 2 weeks after the last dose of study medication - Has an active infectious disease/current infection
Has known allergies, hypersensitivity, or intolerance to minocycline or ketamine or its excipients - Has contraindications to the use of minocycline or ketamine per local prescribing information

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Minocycline

Placebo

Ketamine and Minocycline

Arm Description

Following a 12-day open-label treatment phase (involving ketamine and minocycline), responders may receive oral minocycline twice daily for up to 6 weeks in a blinded manner. In addition, non-responders may receive oral minocycline twice daily for up to 6 weeks in an open-label manner.

Following a 12-day open-label treatment phase (involving ketamine and minocycline), responders may receive placebo twice daily for up to 6 weeks in a blinded manner

All patients will receive 6 IV infusions of ketamine and oral minocycline twice daily during a 12-day open-label treatment phase

Outcomes

Primary Outcome Measures

Proportion of patients (among responders) who survive relapse-free

The Montgomery-Asberg Depression Rating Scale (MADRS) measures depression severity and detects changes due to antidepressant treatment. The test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total score of 60. Higher scores represent a more severe condition. Relapse is defined as MADRS ≥ 30.

Secondary Outcome Measures

Change in MADRS total score among non-responders from pre-randomization to end-of-study

Change in the MADRS total score from baseline during IV ketamine treatment phase

Change in the MADRS total score from baseline after IV ketamine treatment phase

Response (reduction ≥ 50% in MADRS total score relative to baseline) rate during IV ketamine treatment phase

Time to relapse (among responders) following completion of the IV ketamine infusion schedule and after first dose of minocycline/placebo

Change in C-SSRS from baseline to any time in the study

The Columbia Suicide Severity Rating Scale (C-SSRS) is a clinical interview to assess severity and track suicidal events providing a summary of both suicidal ideation and behavior to identify the level and type of suicidality present.

Full Information

NCT ID

NCT01809340

First Posted

March 8, 2013

Last Updated

June 29, 2015

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT01809340

Brief Title

The Effect of Minocycline on Relapse After Successful Intravenous Ketamine/Minocycline-induced Symptoms Response in Subjects With Depression

Official Title

An Exploratory, Blinded, Randomized, Placebo-controlled Study in Subjects With Depressive Disorder to Investigate the Effect of Minocycline on Relapse After Successful Intravenous Ketamine/Minocycline-induced (Partial) Symptoms Response

Study Type

Interventional

2. Study Status

Record Verification Date

June 2015

Overall Recruitment Status

Terminated

Why Stopped

study team decision because of IP supply issue and necessary amendment to protocol

Study Start Date

June 2013 (undefined)

Primary Completion Date

July 2014 (Actual)

Study Completion Date

July 2014 (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

The purpose of this study is to assess whether the antidepressant effect from intravenous (IV) ketamine treatment can be maintained by minocycline compared to placebo after IV ketamine treatment is stopped.

Detailed Description

This is a placebo-controlled (i.e., an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), double-blind (neither physician nor patient knows the treatment that the patient receives) randomized (the drug is assigned by chance) study in patients with Major Depressive Disorder (MDD) and Bipolar Disorder Type II. The study is designed to assess whether the antidepressant response to treatment with intravenous (IV) ketamine can be maintained by treatment with minocycline in patients with MDD and Bipolar Depression Type II (compared to placebo). Both hospitalized patients as well as patients being treated as an outpatient for their current episode of depression can qualify for participation in this study. The study has four sequential phases: if eligibility for the study has been confirmed during the 21-day screening phase, the patients will enter a 12-day open-label (ie, patient and physician know the intervention that is being administered) treatment phase during which the patient will receive 6 open-label IV infusions of 0.5 mg/kg ketamine on Day 1, 3, 5, 8, 10 and 12 in combination with open-label minocycline, orally administered twice daily. All patients will remain at the study site for at least 4 hours after the IV ketamine administrations. Response to treatment will be assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) which is designed to measure the overall severity of depressive symptoms. Patients responding to ketamine/minocycline treatment will be randomized to receive minocycline or placebo for 6 weeks during a 6-week blinded treatment phase or until relapse. A patient will be defined as a "ketamine responder" if there is a 50% or more decrease in comparison to baseline values (Day 1 predose) in the MADRS total score performed at 3 to 4 hours postdose on Days 8, 10, or 12, with a 40% or more decrease from baseline in the MADRS total score on Day 12. Patients not responding to treatment with ketamine/minocycline will be given the option to receive 100 mg minocycline twice daily as open-label treatment for a maximum of 6 weeks. The patients (both responders and non-responders) will have weekly visits following last dose of ketamine until Day 54 (responders/non-responders) or until relapse (responders) whichever comes first, to determine the duration of the antidepressant effect and to assess safety and tolerability after completion of treatment. Upon completion of the study (Day 54) or at time of relapse all patients will have an end-of-study visit. All patients can return to standard of care treatment at the end of the study. The total study duration for each patient will be maximally 11 weeks.

6. Conditions and Keywords

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

Depressive Disorder

Keywords

Depressive Disorder, Major Depressive Disorder, Depression, Bipolar Disorder Type II, Anti-depressant, Ketamine, Minocycline

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

29 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Minocycline

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Following a 12-day open-label treatment phase (involving ketamine and minocycline), responders may receive placebo twice daily for up to 6 weeks in a blinded manner

Arm Title

Ketamine and Minocycline

Arm Type

Experimental

Arm Description

All patients will receive 6 IV infusions of ketamine and oral minocycline twice daily during a 12-day open-label treatment phase

Intervention Type

Drug

Intervention Name(s)

Minocycline

Intervention Description

In the 12-day open-label treatment phase, patients will self administer oral minocycline 200 mg on Day 1, 100 mg twice daily on Days 2 to 11, and 100 mg on the morning of Day 12. In the 6-week blinded treatment phase, responders may self administer oral minocycline 100 mg twice daily from the evening of Day 12 for up to 6 weeks (Day 54), or until relapse, whichever comes first. In the 6-week open-label treatment phase, non-responders may self administer oral minocycline 100 mg twice daily from the evening of Day 12 for up to 6 weeks (Day 54).

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Patients in the 6-week blinded treatment phase, may self administer placebo twice daily from the evening of Day 12 for up to 6 weeks (Day 54), or until relapse, whichever comes first.

Intervention Type

Drug

Intervention Name(s)

Ketamine

Intervention Description

In the 12-day open-label treatment phase, all patients will receive 1 IV infusion of 0.5 mg/kg ketamine over 40 minutes on Days 1, 3, 5, 8, 10 and 12.

Primary Outcome Measure Information:

Title

Proportion of patients (among responders) who survive relapse-free

Description

Time Frame

Day 54

Secondary Outcome Measure Information:

Title

Change in MADRS total score among non-responders from pre-randomization to end-of-study

Description

Time Frame

From Day 12 to Day 54

Title

Change in the MADRS total score from baseline during IV ketamine treatment phase

Description

Time Frame

Days 1, 3, 5, 8, 10 and 12

Title

Change in the MADRS total score from baseline after IV ketamine treatment phase

Description

Time Frame

Days 1, 20, 27, 34, 41, 48, and 54

Title

Response (reduction ≥ 50% in MADRS total score relative to baseline) rate during IV ketamine treatment phase

Description

Time Frame

Days 1, 3, 5, 8, 10, and 12

Title

Time to relapse (among responders) following completion of the IV ketamine infusion schedule and after first dose of minocycline/placebo

Description

Time Frame

From Day 12 to Day 54

Title

Change in C-SSRS from baseline to any time in the study

Description

Time Frame

Days 1, 12, and 54

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnostic criteria for moderate to severe major depressive disorder (MDD), without psychotic features, or Bipolar Disorder Type II Patients should have an Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30) total score ≥ 34 at Screening and at Day 1 (predose) Patients with major depressive disorder should have failed at least two adequate treatment courses (dose and duration) with antidepressant therapy, one of which is in the current episode Patients should not have received electroconvulsive therapy (ECT) in the current episode but could be those for whom ECT is considered Patients with bipolar depression (BPD) Type II must have been taking a stable dose of a mood-stabilizing medication (e.g., lithium, valproate, carbamazepine, lamotrigine, antipsychotic agents) for at least 4 weeks, dosed clinically to target the therapeutic range Patients currently taking an antidepressant(s) must have received at least 2 weeks of stable antidepressant therapy at the time of Screening Doses of current antidepressant therapies should remain the same for the duration of the study 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: Has a current DSM-IV axis I diagnosis other than MDD or BPD Type II at screening (except for co-morbid anxiety disorders) Has a diagnosis of substance abuse or dependence within 6 months prior to screening evaluation (nicotine and caffeine dependence are not exclusionary) Patient is currently taking more than 4 psychotropic medications at Day 1 (predose) Has an autoimmune disorder such as Crohn's disease, rheumatoid arthritis, psoriasis currently treated with/requiring treatment with immunomodulatory therapies Has any significant cardiovascular, respiratory, neurologic, renal, hepatic, endocrine, or immunologic diseases based on screening examination Has uncontrolled hypertension (diastolic blood pressure ≥ 90 mmHg), despite diet, exercise or a stable dose of an allowed antihypertensive treatment, at Screening or Day 1 (predose) Has planned vaccination within 2 weeks prior to the first dose of study medication through 2 weeks after the last dose of study medication - Has an active infectious disease/current infection Has known allergies, hypersensitivity, or intolerance to minocycline or ketamine or its excipients - Has contraindications to the use of minocycline or ketamine per local prescribing information

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

Duffel

Country

Belgium

City

Lede

Country

Belgium

City

Leuven

Country

Belgium

City

Besancon

Country

France

City

Clermont Ferrand

Country

France

City

Nimes Cedex 9

Country

France

City

Leiden

Country

Netherlands

City

Alicante

Country

Spain

City

Barcelona

Country

Spain

City

Coslada

Country

Spain

City

Madrid

Country

Spain

City

Zamora

Country

Spain

12. IPD Sharing Statement

Links:

URL

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=3625&filename=CR100957_CSR.pdf

Description

An exploratory, blinded, randomized, placebo-controlled study in subjects with depressive disorder to investigate the effect of minocycline on relapse after successful intravenous ketamine/minocycline-induced (partial) symptoms response

Learn more about this trial

The Effect of Minocycline on Relapse After Successful Intravenous Ketamine/Minocycline-induced Symptoms Response in Subjects With Depression

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