Research Study for Major Depressive Disorder: Investigation of Glutamate Medications

• ClinicalTrials.gov Identifier: NCT00419003
• Recruitment Status: Completed
• First Posted: January 5, 2007
• Results First Posted: March 21, 2016
• Last Update Posted: July 31, 2019
• Sponsor: Baylor College of Medicine
• 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 Description

Brief Summary:

This study is examining the safety and effectiveness of two medications, ketamine and riluzole, in treating patients with treatment resistant major depressive disorder. This study will also examine the effectiveness of an FDA approved drug called lamotrigine in decreasing the potential side effects associated with ketamine.

Condition or disease	Intervention/treatment	Phase
Major Depression	Drug: Lamotrigine; Drug: Ketamine; Drug: Riluzole	Phase 4

Detailed Description:

This research proposal will investigate a glutamate-modulating agent, riluzole, in treatment-resistant patients who exhibit an acute, sustained response to a single dose of intravenous (IV) racemic ketamine. Fifty ketamine-responders will be randomized to riluzole or placebo in a 4-week, randomized, double-blind, continuation-phase study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Continuation Riluzole in the Prevention of Relapse Following Ketamine in Major Depression
• Study Start Date: December 2006
• Actual Primary Completion Date: July 2008
• Actual Study Completion Date: September 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Lamotrigine Pre-Treatment; 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. 300 mg of lamotrigine 2 hrs prior to ketamine infusion. Responders were randomized to one of two continuation pharmacotherapy groups, receiving either two capsules of riluzole 50 mg each (100 mg/d) or matching pill placebo under double-blind conditions.	Drug: Lamotrigine; anticonvulsant medication; Other Name: lamictal; Drug: Ketamine; subanesthetic dose of NMDAR antagonist; Other Name: ketalar; Drug: Riluzole; glutamate release inhibitor; Other Name: rilutek
Placebo Comparator: Placebo Pre-Treatment; 2 hours prior to ketamine infusion each patient received three capsules of placebo identical in size, weight, appearance, and taste to the lamotrigine tablets. Responders were randomized to one of two continuation pharmacotherapy groups, receiving either two capsules of riluzole 50 mg each (100 mg/d) or matching pill placebo under double-blind conditions.	Drug: Ketamine; subanesthetic dose of NMDAR antagonist; Other Name: ketalar; Drug: Riluzole; glutamate release inhibitor; Other Name: rilutek

Outcome Measures

Primary Outcome Measures :

1. Montgomery-Asberg Depression Rating Scale (MARDS) Score (Acute Response to IV Ketamine in Patients With Treatment Resistant Major Depression) [ Time Frame: 24 Hours ]
   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.

Other Outcome Measures:

1. Efficacy of Lamotrigine in Decreasing IV Ketamine Psychotomimetic Side Effects [ Time Frame: 24, 48, or 72-hrs ]
   Response rate and side effect differences to IV ketamine infusion based on lamotrigine and placebo pretreatment groups

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female patients, 21- 70 years of age
2. Subjects have a history of at least one previous episode of depression prior to the current episode (recurrent major depressive disorder) or have chronic major depressive disorder (at least two years' duration)
3. Subjects have not responded to an adequate trial of one antidepressant in the current episode

Exclusion Criteria:

1. Female subjects who are either pregnant or nursing
2. Serious, unstable illnesses
3. Any previous use or treatment with ketamine, or riluzole
4. Past intolerance to lamotrigine, including drug rash

Contacts and Locations

Locations

United States, New York

Mount Sinai School of Medicine

New York, New York, United States, 10029

Sponsors and Collaborators

Baylor College of Medicine

National Alliance for Research on Schizophrenia and Depression

National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: Sanjay Mathew, MD; Baylor College of Medicine

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wan LB, Levitch CF, Perez AM, Brallier JW, Iosifescu DV, Chang LC, Foulkes A, Mathew SJ, Charney DS, Murrough JW. Ketamine safety and tolerability in clinical trials for treatment-resistant depression. J Clin Psychiatry. 2015 Mar;76(3):247-52. doi: 10.4088/JCP.13m08852.

Price RB, Nock MK, Charney DS, Mathew SJ. Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biol Psychiatry. 2009 Sep 1;66(5):522-6. doi: 10.1016/j.biopsych.2009.04.029. Epub 2009 Jul 9.

Mathew SJ, Murrough JW, aan het Rot M, Collins KA, Reich DL, Charney DS. Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial. Int J Neuropsychopharmacol. 2010 Feb;13(1):71-82. doi: 10.1017/S1461145709000169. Epub 2009 Mar 17.

• Responsible Party: Sanjay Johan Mathew, MD, Baylor College of Medicine
• ClinicalTrials.gov Identifier: NCT00419003
• Other Study ID Numbers: 05-0850; 5M01RR000071-46 ( U.S. NIH Grant/Contract )
• First Posted: January 5, 2007
• Results First Posted: March 21, 2016
• Last Update Posted: July 31, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Depression; Depressive Disorder, Major; Behavioral Symptoms; Depressive Disorder; Mood Disorders; Mental Disorders; Lamotrigine; Ketamine; Riluzole; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anticonvulsants; Calcium Channel Blockers; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Sodium Channel Blockers