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

NCT02772211 | Unknown Phase 4 DMC

• 1 other identifier: 2853-15-SMC
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (1)

• Montgomery Asberg Depression Scale (MADRS)

  A diagnostic questionnaire, measuring the severity of depressive episodes.

  screening criteria, after third ketamine infusions

Other Outcomes (9)

• Hamilton depression Rating Scale

  Up to ten days pre first ketamine administration, after third ketamine infusion, after sixth ketamine infusion, week 7, week 11, 2 months after study completion

• Clinical Global Severity Scale

  Up to ten days pre first ketamine administration, after third ketamine infusion, after sixth ketamine infusion, week 7, week 11, 2 months after study completion

• Clinical Global Improvement

  after third ketamine infusion, after sixth ketamine infusion, week 7, week 11, 2 months after study completion

Study Arms (2)

D-cycloserine

EXPERIMENTAL

Participants in this group would receive 6 infusions of ketamine. Participants who demonstrate symptoms reduction following ketamine infusions would receive oral D-cycloserine, titrated slowly up to 1000mg/d over the next 8 weeks.

Drug: Ketamine; Drug: D-cycloserine

Placebo

PLACEBO COMPARATOR

Participants in this group would receive 6 infusions of ketamine. Participants who demonstrate symptoms reduction following ketamine infusions would receive oral Placebo pills, titrated slowly up to 1000mg/d over the next 8 weeks.

Drug: Ketamine; Drug: Placebo

Interventions

Ketamine DRUG

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.

D-cycloserine; Placebo

D-cycloserine DRUG

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

Also known as: D-cycloserine, Cycloserine, DCS

D-cycloserine

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18-75 meeting DSM-V criteria for moderate-severe depression (MADRS≥25), who did not respond to two adequate antidepressant courses of treatment. Subjects will be required to continue on a stable dose of any psychotropic medication they are taking, for 8 weeks prior to ketamine infusion. Participants who respond to ketamine (reduction of 25% in symptoms) would be invited to participate in a second stage of the experiment, in which participants would consume DCS for 8 weeks (weeks 4-11).

Sponsors & Collaborators

• Sheba Medical Center: lead
• Teva Pharmaceuticals USA: collaborator
• Tel Aviv University: collaborator

Study Sites (1)

Psychiatry Clinic - Sheba Medical Center

Ramat Gan, Israel

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Ketamine; Cycloserine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Central Study Contacts

Revital Amiaz, MD

CONTACT

+972-542378757; revital.amiaz@sheba.health.gov.il

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: May 10, 2016
• First Posted: May 13, 2016
• Study Start: June 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: January 1, 2017
• Last Updated: May 13, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)