Research Study for Major Depressive Disorder: Investigation of Glutamate Medications

NCT00419003 | Completed Phase 4 Results

• 2 other identifiers: 05-08505M01RR000071-46
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depression

Outcome Measures

Primary Outcomes (1)

• Montgomery-Asberg Depression Rating Scale (MARDS) Score (Acute Response to IV Ketamine in Patients With Treatment Resistant Major Depression)

  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.

  24 Hours

Other Outcomes (1)

• Efficacy of Lamotrigine in Decreasing IV Ketamine Psychotomimetic Side Effects

  24, 48, or 72-hrs

Study Arms (2)

Lamotrigine Pre-Treatment

EXPERIMENTAL

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; Drug: Ketamine; Drug: Riluzole

Placebo Pre-Treatment

PLACEBO COMPARATOR

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; Drug: Riluzole

Interventions

Lamotrigine DRUG

anticonvulsant medication

Also known as: lamictal

Lamotrigine Pre-Treatment

Ketamine DRUG

subanesthetic dose of NMDAR antagonist

Also known as: ketalar

Lamotrigine Pre-Treatment; Placebo Pre-Treatment

Riluzole DRUG

glutamate release inhibitor

Also known as: rilutek

Lamotrigine Pre-Treatment; Placebo Pre-Treatment

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, 21- 70 years of age
• 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)
• Subjects have not responded to an adequate trial of one antidepressant in the current episode

You may not qualify if:

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

Sponsors & Collaborators

• Baylor College of Medicine: lead
• National Alliance for Research on Schizophrenia and Depression: collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Related Publications (3)

• 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.

  PMID: 25271445 DERIVED

• 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.

  PMID: 19545857 DERIVED

• 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.

  PMID: 19288975 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Lamotrigine; Ketamine; Riluzole

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Thiazoles; Sulfur Compounds; Benzothiazoles; Azoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Sanjay Mathew
• Organization: Baylor College of Medicine

sjmathew@bcm.edu

7137985439

Study Officials

• Sanjay Mathew, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: January 4, 2007
• First Posted: January 5, 2007
• Study Start: December 1, 2006
• Primary Completion: July 1, 2008
• Study Completion: September 1, 2008
• Last Updated: July 31, 2019
• Results First Posted: March 21, 2016

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)