D-cycloserine for Relapse Prevention Following Intravenous Ketamine in Treatment-resistant Depression

Summary

This is a two-stage experiment; the first stage is an open label trial in which participants receive six intravenous (IV) treatments of ketamine. The second stage includes participants that responded to ketamine (i.e. reduction of 25% in their symptoms of depression, as measured by the Montgomery Asberg Depression Scale MADRS). The second stage is a double-blind, controlled clinical trial of D-cycloserine (DCS) vs. placebo, as maintenance treatment in patients who responded to ketamine treatment. The aim of the study is to determine whether 8 weeks of DCS maintenance therapy will prevent relapse of depressive symptoms following ketamine infusions

Conditions

• Treatment Resistant Depression

Interventions

DRUG

Ketamine

Patients will undergo 6 ketamine infusions within a 3-week period. Intravenous ketamine will be administrated by a senior anesthesiologist and under the supervision of a senior psychiatrist hence ensuring patient safety. The procedure will be explained in detail to each patient, and written consent will be obtained. After a psychiatric and medical evaluation by a senior psychiatrist and a senior anesthesiologist, patients will be given ketamine infusion added on to their antidepressant therapy. A slow ketamine infusion of 0.5mg/kg over 40 minutes will be given to the patients. Patients will be monitored by the experienced staff which includes a senior anesthesiologist and a nurse as well as a psychiatrist who will be available nearby. All patients will be monitored continuously for heart rate and rhythm and oxygen saturation, and blood pressure will be measured at 10 minutes intervals.

DRUG

D-cycloserine

Following completion of Ketamine infusions. patients in the experimental group will start receiving D-cycloserine pills titrated slowly up to 1000mg/d over the next 8 weeks \[2\] in the following manner: 1. Week 4: Days 22-24 - 250mg/d, one pill per day Well-being assessment and adverse effect evaluation before drug elevation. 2. Mid-week 4 to end of week 6: Days 25-42 - 500mg/d, two pills per day 3. Week 7: Day 43-49 - 750mg/d, three pills per day 4. Weeks 8-11: Days 50-77 - 1000mg/d four pills per day

DRUG

Placebo

Following completion of Ketamine infusions. patients in the experimental group will start receiving placebo titrated slowly up to 1000mg/d over the next 8 weeks \[2\] in the following manner: 1. Week 4: Days 22-24 - 250mg/d, one pill per day Well-being assessment and adverse effect evaluation before drug elevation. 2. Mid-week 4 to end of week 6: Days 25-42 - 500mg/d, two pills per day 3. Week 7: Day 43-49 - 750mg/d, three pills per day 4. Weeks 8-11: Days 50-77 - 1000mg/d four pills per day

Sponsors & Collaborators

• Teva Pharmaceuticals USA

  collaborator INDUSTRY

• Tel Aviv University

  collaborator OTHER

• Sheba Medical Center

  lead OTHER_GOV

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-06-30

Primary Completion

2016-12-31

Completion

2017-01-31

Countries

• Israel

Study Locations