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

NCT01809340 | Terminated Phase 2

• 3 other identifiers: CR100957KETIVEDI20012012-002954-21
• Study Type: interventional
• Target: 29
• Locations: 4 countries
• Sites: 12

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.

Conditions

Depressive Disorder

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 54

Secondary Outcomes (6)

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

  From Day 12 to Day 54

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

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

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

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

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

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

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

  From Day 12 to Day 54

Study Arms (3)

Minocycline

EXPERIMENTAL

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.

Drug: Minocycline

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Ketamine and Minocycline

EXPERIMENTAL

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

Drug: Minocycline; Drug: Ketamine

Interventions

Minocycline DRUG

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).

Ketamine and Minocycline; Minocycline

Placebo DRUG

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.

Placebo

Ketamine DRUG

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.

Ketamine and Minocycline

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Has a current DSM-IV axis I diagnosis other than MDD or BPD Type II at screening (except for co-morbid anxiety disorders)
• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (12)

Unknown Facility

Duffel, Belgium

Location

Unknown Facility

Lede, Belgium

Location

Unknown Facility

Leuven, Belgium

Location

Unknown Facility

Besançon, France

Location

Unknown Facility

Clermont-Ferrand, France

Location

Unknown Facility

Nîmes, France

Location

Unknown Facility

Leiden, Netherlands

Location

Unknown Facility

Alicante, Spain

Location

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Coslada, Spain

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

Zamora, Spain

Location

Related Links

• 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

MeSH Terms

Conditions

Depressive Disorder; Depressive Disorder, Major; Depression; cyclopia sequence

Interventions

Minocycline; Ketamine

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2013
• First Posted: March 12, 2013
• Study Start: June 1, 2013
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: June 30, 2015

Record last verified: 2015-06

Locations

FR (3); ES (5); BE (3); NL (1)