Major DepressionPhase 4NCT00419003

Research Study for Major Depressive Disorder: Investigation of Glutamate Medications

A Phase 4 study testing Lamotrigine, Ketamine and Riluzole in people with Major Depression, run by Baylor College of Medicine at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 21 to 70 years
Conditions the study is for: Major Depression
What is being tested?: Lamotrigine, Ketamine and Riluzole
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 26 participants
Where: 1 siteUnited States
Study dates: Dec 2006to Sep 2008
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Mount Sinai School of Medicine
New York, New York, 10029

Other trials in United States

About this study

Official title: Continuation Riluzole in the Prevention of Relapse Following Ketamine in Major Depression

Read the 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.

Conditions: Major Depression
Being tested: Lamotrigine, Ketamine, Riluzole
Medical subject headings: Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LamotrigineDrug
Also called lamictal
anticonvulsant medication
KetamineDrug
Also called ketalar
subanesthetic dose of NMDAR antagonist
RiluzoleDrug
Also called rilutek
glutamate release inhibitor

Study groups in NCT00419003
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: Ketamine; Drug: Riluzole

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 24 Hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2006Sep 2008

First posted5 Jan 2007 (estimated)
Study startDec 2006
Primary completionJul 2008
Study completionSep 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Major DepressionStudies of the same condition, open and under way.
More trials run by Baylor College of MedicineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00419003
Sponsor's protocol ID: 05-0850
Other IDs: 5M01RR000071-46
Status last verified: Jul 2019
First submitted: 4 Jan 2007
Last updated: 31 Jul 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Publications

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.
PubMed 25271445
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.
PubMed 19545857
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.
PubMed 19288975

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Major Depression trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Continuation Riluzole in the Prevention of Relapse Following Ketamine in Major Depression
ClinicalTrials.gov ID: NCT00419003
Acronym / sponsor ID: 05-0850
Conditions: Major Depression
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: Baylor College of MedicineUniversity, hospital or other
Collaborators: National Alliance for Research on Schizophrenia and Depression, National Center for Research Resources (NCRR)
Study start: Dec 2006
Primary completion: Jul 2008 (actual)
Study completion: Sep 2008 (actual)
First posted: 5 Jan 2007 (estimated)
Results: Posted 21 Mar 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Lamotrigine Pre-Treatment	Experimental	Drug: Lamotrigine, Drug: Ketamine, Drug: RiluzolePatients 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.
Placebo Pre-Treatment	Placebo comparator	Drug: Ketamine, Drug: Riluzole2 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.

Who may qualify

Ages: 21 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LamotrigineAlso: lamictalanticonvulsant medication	Drug	Lamotrigine Pre-Treatment
KetamineAlso: ketalarsubanesthetic dose of NMDAR antagonist	Drug	Lamotrigine Pre-Treatment, Placebo Pre-Treatment
RiluzoleAlso: rilutekglutamate release inhibitor	Drug	Lamotrigine Pre-Treatment, Placebo Pre-Treatment

Primary outcome

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.

Results and safety

Results posted to the registry on 21 Mar 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lamotrigine Pre-Treatment (Phase I)/Riluzole (Phase II)	13	7
Placebo Pre-Treatment (Phase I)/Placebo (Phase II)	13	7

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

Time frame: 24 Hours. Mean (95% Confidence Interval). Unit: scores on a scale

Measure	Riluzole Group n = 13	Placebo n = 13
Value	24.4 (15.9 to 33.0)	22.0 (14.9 to 29.1)

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Riluzole Group	0 of 6 (0%)	6 of 6 (100%)	Not reported
Placebo	0 of 8 (0%)	5 of 8 (62.5%)	Not reported
Ketamine	0 of 26 (0%)	26 of 26 (100%)	Not reported
Lamotrigine Pre-Treatment	0 of 13 (0%)	5 of 13 (38.5%)	Not reported
Placebo Pre-Treatment	0 of 13 (0%)	0 of 13 (0%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 25271445Wan 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.
Derived from this study: PubMed 19545857Price 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.
Derived from this study: PubMed 19288975Mathew 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.
Individual participant dataSharing planned: No

Related trials for Major Depression

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sanjay Mathew, MD principal investigator

Baylor College of Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Lamotrigine, Ketamine and Riluzole in people with Major Depression, run by Baylor College of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Montgomery-Asberg Depression Rating Scale (MARDS) Score (Acute Response to IV Ketamine in Patients With Treatment Resistant Major Depression) (time frame: 24 Hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00419003, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2019.