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Research Study for Major Depressive Disorder: Investigation of Glutamate Medications

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ClinicalTrials.gov Identifier: NCT00419003
Recruitment Status : Completed
First Posted : January 5, 2007
Results First Posted : March 21, 2016
Last Update Posted : March 21, 2016
Sponsor:
Collaborators:
National Alliance for Research on Schizophrenia and Depression
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Sanjay Johan Mathew, Baylor College of Medicine

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Major Depression
Interventions Drug: Lamotrigine
Drug: Ketamine
Drug: Riluzole
Enrollment 26
Recruitment Details The intent-to-treat sample (n=26) was recruited from media/internet advertising (14), psychiatrist referral (8), or self-referral from the New York Mood Disorders Support Group (4). Patients had marked depressive severity, chronicity, and anxiety comorbidity, and were highly pharmacotherapy-resistant.
Pre-assignment Details 2-wk psychotropic medication washout period (4 wk for fluoxetine)
Arm/Group Title Lamotrigine Pre-Treatment (Phase I)/Riluzole (Phase II) Placebo Pre-Treatment (Phase I)/Placebo (Phase II)
Hide Arm/Group Description Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth. All non responders were exited from the study. All responders (in both the lamotrigine and placebo pre-treatment groups were treated as one group and randomized into either treatment with riluzole or placebo for Phase II) Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth. All non responders were exited from the study. All responders (in both the lamotrigine and placebo pre-treatment groups were treated as one group and randomized into either treatment with riluzole or placebo for Phase II)
Period Title: Phase I, Ketamine Infusion
Started 13 13
Completed 7 7
Not Completed 6 6
Reason Not Completed
Lack of Efficacy             6             6
Period Title: Phase 2, Riluzole/Placebo Follow-Up
Started 6 [1] 8 [1]
Completed 5 8
Not Completed 1 0
Reason Not Completed
Withdrawal by Subject             1             0
[1]
14 completers of phase I didn’t split up evenly (same way as phase I) in the riluzole/placebo phase.
Arm/Group Title Lamotrigine Pre-Treatment Placebo Pre-Treatment Total
Hide Arm/Group Description Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth. Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth. Total of all reporting groups
Overall Number of Baseline Participants 13 13 26
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants 13 participants 26 participants
48.2  (11.8) 48.2  (11.8) 48.2  (11.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 13 participants 26 participants
Female
5
  38.5%
5
  38.5%
10
  38.5%
Male
8
  61.5%
8
  61.5%
16
  61.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 13 participants 13 participants 26 participants
13 13 26
1.Primary Outcome
Title Montgomery-Asberg Depression Rating Scale (MARDS) Score (Acute Response to IV Ketamine in Patients With Treatment Resistant Major Depression)
Hide Description Montgomery-Asberg Depression Rating Scale, each of the ten items can be scored from 0 (absence of symptoms to 6 most severe) and has a total score range of 0-60. A lower score on a MADRS indicates a less severe depression. The primary outcome for the initial phase of the trial was the 24-h MADRS score, which included all 10 MADRS items.
Time Frame 24 Hours
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Riluzole Group Placebo
Hide Arm/Group Description:
Patients who responded (n=14) to the ketamine infusion (in either the lamotrigine or placebo pre-treatment groups) were randomized into phase II for treatment with either riluzole or placebo. One patient in the riluzole group was discontinued/withdrew consent before completing the study.
Patients who responded (n=14) to the ketamine infusion (in either the lamotrigine or placebo pre-treatment groups) were randomized into phase II for treatment with either riluzole or placebo.
Overall Number of Participants Analyzed 13 13
Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
24.4
(15.9 to 33.0)
22.0
(14.9 to 29.1)
2.Secondary Outcome
Title Efficacy of Lamotrigine in Decreasing IV Ketamine Psychotomimetic Side Effects
Hide Description Response rate and side effect differences to IV ketamine infusion based on lamotrigine and placebo pretreatment groups
Time Frame 24, 48, or 72-hrs
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Riluzole Group Placebo Ketamine Lamotrigine Pre-Treatment Placebo Pre-Treatment
Hide Arm/Group Description Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth. Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth. IV infusion of 0.5 mg/kg of Ketamine Hydrochloride Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth. Patients who met enrolment criteria for phase 1 were randomly allocated to lamotrigine or placebo by a permuted block procedure consisting of blocks of two or four patients. The randomization list was created by a biostatistician with no patient contact. Following baseline ratings, 2 h prior to i.v. ketamine infusion, patients received 300 mg lamotrigine or placebo by mouth.
All-Cause Mortality
Riluzole Group Placebo Ketamine Lamotrigine Pre-Treatment Placebo Pre-Treatment
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Riluzole Group Placebo Ketamine Lamotrigine Pre-Treatment Placebo Pre-Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/6 (0.00%)      0/8 (0.00%)      0/26 (0.00%)      0/13 (0.00%)      0/13 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Riluzole Group Placebo Ketamine Lamotrigine Pre-Treatment Placebo Pre-Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      5/8 (62.50%)      26/26 (100.00%)      5/13 (38.46%)      0/13 (0.00%)    
Nervous system disorders           
Headache   2/6 (33.33%)  6 0/8 (0.00%)  0 26/26 (100.00%)  26 5/13 (38.46%)  5 0/13 (0.00%)  0
Dizziness   1/6 (16.67%)  2 3/8 (37.50%)  3 26/26 (100.00%)  26 0/13 (0.00%)  0/13 (0.00%) 
Fatigue   3/6 (50.00%)  3 2/8 (25.00%)  2 0/26 (0.00%)  5/13 (38.46%)  5 0/13 (0.00%) 
Indicates events were collected by systematic assessment
The open-label administration of ketamine limits interpretation of phase 1 results. The sample size was too small to detect moderators and mediators of response. Third,lack of placebo-controlled efficacy data supporting riluzole's use in depression.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Sanjay Mathew
Organization: Baylor College of Medicine
Phone: 7137985439
Responsible Party: Sanjay Johan Mathew, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00419003     History of Changes
Other Study ID Numbers: 05-0850
5M01RR000071-46 ( U.S. NIH Grant/Contract )
First Submitted: January 4, 2007
First Posted: January 5, 2007
Results First Submitted: September 5, 2013
Results First Posted: March 21, 2016
Last Update Posted: March 21, 2016