Clinical TrialMajor Depressive Disorder (MDD)PlaceboKetamineTerminated

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

Randomised, double-blind, placebo-controlled study (n=29 planned) assessing whether oral minocycline maintains antidepressant response after an open-label IV ketamine induction (0.5 mg/kg, six infusions) in patients with MDD and Bipolar II.

Target Enrollment
29 participants
Study Type
Phase II interventional
Design
Randomized, double Blind

Detailed Description

This parallel, randomised, double-blind trial enrolled patients with moderate to severe major depressive disorder or Bipolar Disorder Type II who completed a 12-day open-label induction of six IV ketamine infusions (0.5 mg/kg) combined with minocycline.

Responders to the induction phase were randomised to oral minocycline 100 mg twice daily or matched placebo for up to 6 weeks to assess maintenance of antidepressant response; non-responders could receive open-label minocycline.

Primary efficacy assessed by MADRS; safety and tolerability monitored throughout with weekly visits until Day 54 or relapse.

Study Protocol

Preparation

sessions

Dosing

6 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Minocycline (blinded)

experimental

Responders randomised to oral minocycline 100 mg twice daily for up to 6 weeks (blinded phase).

Interventions

  • Compound100 mg
    via Oral• twice daily

    Blinded phase: 100 mg twice daily from evening of Day 12 for up to 6 weeks (or until relapse).

  • Compound
    via Oral• open-label induction

    Open-label induction schedule: Day 1 200 mg, Days 2–11 100 mg twice daily, Day 12 100 mg morning.

Placebo (blinded)

placebo

Responders randomised to matched placebo twice daily for up to 6 weeks (blinded phase).

Interventions

  • Placebo
    via Oral• twice daily

    Placebo twice daily from evening of Day 12 for up to 6 weeks (or until relapse).

Ketamine induction

experimental

All participants receive open-label IV ketamine 0.5 mg/kg infusions plus open-label minocycline during a 12-day induction (six infusions).

Interventions

  • Ketamine0.5 mg/kg
    via IV• Days 1,3,5,8,10,12• 6 doses total

    IV infusion over 40 minutes on Days 1,3,5,8,10,12.

  • Compound100 mg
    via Oral• varied/see notes

    Open-label minocycline during induction: Day 1 200 mg, Days 2–11 100 mg twice daily, Day 12 100 mg morning.

Participants

Ages
18 – 80
Sexes
Male & Female

Inclusion Criteria

  • Diagnostic criteria for moderate to severe major depressive disorder (MDD), without psychotic features, or Bipolar Disorder Type II
  • IDS-C30 total score ≥ 34 at Screening and at Day 1 (predose)
  • MDD patients must have failed at least two adequate antidepressant courses, one in current episode
  • No ECT in current episode (but ECT may be considered)
  • Bipolar II patients must be on a stable mood-stabiliser for ≥ 4 weeks
  • Patients on antidepressants must have ≥ 2 weeks stable therapy at Screening
  • Doses of current antidepressant therapies remain the same during study
  • Women must be postmenopausal, surgically sterile, or using highly effective contraception if heterosexually active
  • Heterosexually active men must use double barrier contraception and not donate sperm during study and for 3 months after last dose

Exclusion Criteria

  • Current DSM-IV axis I diagnosis other than MDD or Bipolar II at screening (except comorbid anxiety disorders)
  • Substance abuse or dependence within 6 months prior to screening (nicotine and caffeine allowed)
  • Taking >4 psychotropic medications at Day 1 (predose)
  • Autoimmune disorders requiring immunomodulatory therapy
  • Significant cardiovascular, respiratory, neurologic, renal, hepatic, endocrine, or immunologic disease
  • Uncontrolled hypertension (diastolic ≥ 90 mmHg) at Screening or Day 1 (predose)
  • Planned vaccination within 2 weeks prior to first dose through 2 weeks after last dose
  • Active infectious disease/current infection
  • Known allergy, hypersensitivity, or intolerance to minocycline or ketamine or excipients
  • Contraindications to minocycline or ketamine per local prescribing information

Study Details

Locations

Unknown facility — Duffel, Belgium
Unknown facility — Lede, Belgium
Unknown facility — Leuven, Belgium
Unknown facility — Besançon, France
Unknown facility — Clermont-Ferrand, France
Unknown facility — Nîmes, France
Unknown facility — Leiden, Netherlands
Unknown facility — Alicante, Spain
Unknown facility — Barcelona, Spain
Unknown facility — Coslada, Spain
Unknown facility — Madrid, Spain
Unknown facility — Zamora, Spain

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