Clinical trial NCT01809340: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Depressive Disorder
Keywords: Depressive Disorder
Major Depressive Disorder
Depression
Bipolar Disorder Type II
Anti-depressant
Ketamine
Minocycline
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2013-03-12
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Proportion of patients (among responders) who survive relapse-free
timeFrame: Day 54
Secondary outcomes:
measure: Change in MADRS total score among non-responders from pre-randomization to end-of-study
timeFrame: From Day 12 to Day 54
measure: Change in the MADRS total score from baseline during IV ketamine treatment phase
timeFrame: Days 1, 3, 5, 8, 10 and 12
measure: Change in the MADRS total score from baseline after IV ketamine treatment phase
timeFrame: Days 1, 20, 27, 34, 41, 48, and 54
measure: Response (reduction ≥ 50% in MADRS total score relative to baseline) rate during IV ketamine treatment phase
timeFrame: Days 1, 3, 5, 8, 10, and 12
measure: Time to relapse (among responders) following completion of the IV ketamine infusion schedule and after first dose of minocycline/placebo
timeFrame: From Day 12 to Day 54
measure: Change in C-SSRS from baseline to any time in the study
timeFrame: Days 1, 12, and 54
Other outcomes:
Locations:
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
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: