Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Effect of Minocycline on Relapse After Successful Intravenous Ketamine/Minocycline-induced Symptoms Response in Subjects With 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: NCT01809340
Recruitment Status : Terminated (study team decision because of IP supply issue and necessary amendment to protocol)
First Posted : March 12, 2013
Last Update Posted : June 30, 2015
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE March 8, 2013
First Posted Date  ICMJE March 12, 2013
Last Update Posted Date June 30, 2015
Study Start Date  ICMJE June 2013
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 8, 2013)
Proportion of patients (among responders) who survive relapse-free [ Time Frame: Day 54 ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2013)
  • Change in MADRS total score among non-responders from pre-randomization to end-of-study [ Time Frame: From Day 12 to Day 54 ]
    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.
  • Change in the MADRS total score from baseline during IV ketamine treatment phase [ Time Frame: Days 1, 3, 5, 8, 10 and 12 ]
    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.
  • Change in the MADRS total score from baseline after IV ketamine treatment phase [ Time Frame: Days 1, 20, 27, 34, 41, 48, and 54 ]
    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.
  • Response (reduction ≥ 50% in MADRS total score relative to baseline) rate during IV ketamine treatment phase [ Time Frame: Days 1, 3, 5, 8, 10, and 12 ]
    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.
  • Time to relapse (among responders) following completion of the IV ketamine infusion schedule and after first dose of minocycline/placebo [ Time Frame: From Day 12 to Day 54 ]
    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.
  • Change in C-SSRS from baseline to any time in the study [ Time Frame: Days 1, 12, and 54 ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of Minocycline on Relapse After Successful Intravenous Ketamine/Minocycline-induced Symptoms Response in Subjects With Depression
Official Title  ICMJE 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
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.
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 Depressive Disorder
Intervention  ICMJE
  • Drug: Minocycline
    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).
  • Drug: Placebo
    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.
  • Drug: Ketamine
    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.
Study Arms  ICMJE
  • Experimental: Minocycline
    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.
    Intervention: Drug: Minocycline
  • Placebo Comparator: Placebo
    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
    Intervention: Drug: Placebo
  • Experimental: Ketamine and Minocycline
    All patients will receive 6 IV infusions of ketamine and oral minocycline twice daily during a 12-day open-label treatment phase
    Interventions:
    • Drug: Minocycline
    • Drug: Ketamine
Publications * Not Provided

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: June 27, 2014)
29
Original Estimated Enrollment  ICMJE
 (submitted: March 8, 2013)
80
Actual Study Completion Date  ICMJE July 2014
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 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 Belgium,   France,   Netherlands,   Spain
Removed Location Countries Romania
 
Administrative Information
NCT Number  ICMJE NCT01809340
Other Study ID Numbers  ICMJE CR100957
KETIVEDI2001 ( Other Identifier: Janssen Research & Development, LLC )
2012-002954-21 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date June 2015

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