DepressionPhase 2NCT00026052
Riluzole to Treat Major Depression
A Phase 2 study testing riluzole in people with Depression, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
This study will examine the safety and effectiveness of the drug riluzole (Rilutek® (Registered Trademark)) for short-term treatment of depression symptoms, such as depressed mood, psychomotor retardation, and excessive sleeping. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Depression
- What is being tested?
- riluzole
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2001to Apr 2003
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female subjects, 18 to 70 years of age will be eligible.
- Female subjects of childbearing potential must be using a medically accepted means of contraception.
- Each subject must have a level of understanding sufficient to agree to all required tests and examinations.
- Each subject must understand the nature of the study and must sign an informed consent document.
- Subjects must fulfill the criteria for major depression, recurrent without psychotic features as defined in DSM-IV (296.32, 296.33) based on clinical assessment and confirmed by structured diagnostic interview SCID-P.
- Subjects must have an initial score at Visit 1 and Visit 2 of at least 20 on the MADRS.
Show all 10Show fewer
- Subjects must not have a decrease in the total score of MADRS of greater than or equal 20% during washout (between Visits 1 and 2).
- Subjects must have experienced, in the opinion of the investigator, at least one prior major depressive episode as defined in DSM-IV (not including the current major depressive episode).
- Subjects must have had at least one adequate antidepressant trial (SSRI, bupropion, or venlafaxine) during an episode of major depression (Thase and Rush, 1995; Thase et al., 2000).
- Subjects with current major depressive episode of no more than 24 months will be eligible.
Who cannot join
- Presence of psychotic features.
- Participate in a clinical trial of another investigational drug within 1 month (30 days) prior to study entry (Visit 1).
- Female subjects who are either pregnant or nursing.
- Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
- Subjects with uncorrected hypothyroidism or hyperthyroidism.
- Abnormal levels of serum transaminases (ALT/SGPT; AST/SGOT), current or past blood dyscrasia.
Show all 15Show fewer
- Documented history of hypersensitivity or intolerance to riluzole.
- DSM-IV substance abuse or dependence within the past 90 days.
- Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections prior to Visit 2.
- Treatment with a reversible MAOI, guanethidine, or guanadrel within 1 week or with fluoxetine within 3 weeks prior to Visit 2.
- Treatment with any other concomitant medication with primarily CNS activity, other than specified in Appendix A.
- Treatment with clozapine or ECT within 12 weeks prior to Visit 2.
- Current diagnosis of schizophrenia or other psychotic disorder as defined in the DSM-IV will be excluded.
- Judged clinically to be at serious suicidal risk, with a score of 3 or more on item 3 of the HAMD will be excluded.
- Patients will not be allowed to receive structured psychotherapy during the trial.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Mental Health (NIMH)
Bethesda, Maryland, 20892
About this study
Official title: An Investigation of the Antidepressant Efficacy of an Antiglutamatergic Agent With Neurotrophic Properties in Major Depression
This study will examine the safety and effectiveness of the drug riluzole (Rilutek® (Registered Trademark)) for short-term treatment of depression symptoms, such as depressed mood, psychomotor retardation, and excessive sleeping. Despite the availability of a wide range of antidepressant drugs, studies indicate that 30 to 40 percent of patients with major depression do not respond to first-line antidepressant treatment with drugs such as fluoxetine, upropion, venlafaxine and others. Riluzole, which is approved by the Food and Drug Administration (FDA) for amyotrophic lateral sclerosis (ALS), causes chemical changes in the brain that may also have antidepressant properties.
Patients between 18 and 70 years of age with major depressive disorder without psychotic features may be eligible for this 2-stage 7-week study. Candidates will be screened with a medical history and physical examination, including an electrocardiogram (EKG), blood and urine tests, and a psychiatric evaluation. A
Read more
blood or urine sample will be tested for illegal drugs.Women of childbearing potential will have a pregnancy test.
Participants will complete stage 1 of the study, which lasts 1 week, and may then continue with stage 2 for an additional 6 weeks. At the start of the study, patients will be tapered off all psychiatric medicines and will begin treatment with a placebo (a sugar pill formulated to look like the active drug). At some point, they will be switched from placebo to riluzole. In addition, participants will undergo the following procedures:
- Physical examination and electrocardiograms (EKG) at the beginning and end of the study, with vital signs (temperature, blood pressure and heart rate) checked daily
- Weekly 1-hour interviews consisting of psychiatric and psychomotor rating scales to assess treatment response
- Weekly blood tests to measure blood levels of riluzole and evaluate drug side effects
At the end of the study, participants' psychiatric status will be reassessed and appropriate long-term psychiatric treatment arranged.
Patients, ages 18 to 70 with a diagnosis of major depression without psychotic features, will in this pilot study (single arm, single blind) receive riluzole (50-200 mg/day) for a period of 6 weeks. Acute efficacy will be determined by demonstrating a greater response rate using specified criteria.
Approximately 25 patients will enter the study to obtain 22 subjects who complete the 6 weeks of acute riluzole treatment. Therefore, if 7/22 patients or greater have greater than 50% improvement on the primary efficacy measure, then based on statistically guidelines from the Optimal Two Stage Design for Clinical Trials, a controlled trial would be indicated to scientifically confirm the signal observed in the single arm trial.
Read the detailed description
Major affective disorders are common, severe, chronic and often life-threatening illnesses. Major depression contributes to significant morbidity and mortality. Impairment in physical and social functioning resulting from depression can be just as severe as other chronic medical illnesses. Suicide is the cause of death in 10-20% of individuals with either bipolar or recurrent depressive disorders.
Despite the availability of a wide range of antidepressant drugs, clinical trials indicate that 30% to 40% of patients with major depression fail to respond to first-line antidepressant treatment, despite adequate dosage, duration, and compliance. Thus, there is a clear need to develop novel and improved therapeutics for unipolar and bipolar depression. Recent preclinical studies suggest that antidepressants may exert delayed indirect effects on the glutamatergic system. Furthermore, a growing body of data suggests that mood disorders are associated with regional volumetric reductions, and cell loss and atrophy. It is thus noteworthy that lamotrigine, which, among other effects reduces glutamate release, has antidepressant effects, and a pilot study has suggested that NMDA antagonists may have antidepressant effects. Together, this data suggests that the glutamatergic system may play a role in the pathophysiology and treatment of depression, and that agents, which more directly reduce glutamatergic neurotransmission, may represent a novel class of antidepressants.
Riluzole, an agent that is Food and Drug Administration-approved for Amyotrophic Lateral Sclerosis has significant antiglutamatergic and neuroprotective properties, may prove to have antidepressant properties in depressed patients. In this study, we propose to investigate the potential antidepressant efficacy of riluzole, an agent which reduces glutamatergic throughput via inhibition of its release, which also exerts robus neurotrophic effects.
This is a 6-week single-arm, single-blind study that will examine the efficacy and safety of riluzole in patients with major depression without psychotic features.
The study has two Study Periods. Study Period I is the washout phase that will last 7 days. Study Period II is a monotherapy 6-week acute treatment phase in which the efficacy and tolerability of riluzole is compared to baseline.
Patients, ages 18 to 60 with a diagnosis of major depression without psychotic features, will in this pilot study (single arm, single-blind) receive riluzole (50-200 mg/day) for a period of 6 weeks. Acute efficacy will be determined by demonstrating a greater response rate using specified criteria.
Approximately 25 patients will enter the study to obtain 22 subjects who complete the 6 weeks of acute riluzole treatment. Therefore if 7/22 patients or greater have greater than 50% improvement on the primary efficacy measure, then based on statistically guidelines from the Optimal Two Stage Design for Clinical Trials, a controlled trial would be indicated to scientifically confirm the signal observed in the single arm trial.
- Conditions
- Depression
- Being tested
- riluzole
- Keywords
- Riluzole, Neuroprotective, Open-Label Study, Glutamate Dysfunction, Unipolar Depression, Antidepressant, Depression, Major Depression
- Medical subject headings
- Depression, Depressive Disorder, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
riluzoleDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2001 (estimated)
- Study startNov 2001
- Study completionApr 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The 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 2
- Primary purpose
- Treatment
- Enrolment
- 31 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00026052
- Sponsor's protocol ID
- 020034
- Other IDs
- 02-M-0034
- Status last verified
- Apr 2003
- First submitted
- 8 Nov 2001
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Aronowski J, Strong R, Grotta JC. Combined neuroprotection and reperfusion therapy for stroke. Effect of lubeluzole and diaspirin cross-linked hemoglobin in experimental focal ischemia. Stroke. 1996 Sep;27(9):1571-6; discussion 1576-7. doi: 10.1161/01.str.27.9.1571.
PubMed 8784132Altamura CA, Mauri MC, Ferrara A, Moro AR, D'Andrea G, Zamberlan F. Plasma and platelet excitatory amino acids in psychiatric disorders. Am J Psychiatry. 1993 Nov;150(11):1731-3. doi: 10.1176/ajp.150.11.1731.
PubMed 8214185Abe K, Aoki M, Kawagoe J, Yoshida T, Hattori A, Kogure K, Itoyama Y. Ischemic delayed neuronal death. A mitochondrial hypothesis. Stroke. 1995 Aug;26(8):1478-89. doi: 10.1161/01.str.26.8.1478.
PubMed 7631357
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigation of the Antidepressant Efficacy of an Antiglutamatergic Agent With Neurotrophic Properties in Major Depression
- ClinicalTrials.gov ID
- NCT00026052
- Acronym / sponsor ID
- 020034
- Conditions
- Depression
- Keywords
- Riluzole, Neuroprotective, Open-Label Study, Glutamate Dysfunction, Unipolar Depression, Antidepressant, Depression, Major Depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- Nov 2001
- Study completion
- Apr 2003
- First posted
- 9 Nov 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine the safety and effectiveness of the drug riluzole (Rilutek® (Registered Trademark)) for short-term treatment of depression symptoms, such as depressed mood, psychomotor retardation, and excessive sleeping. Despite the availability of a wide range of antidepressant drugs, studies indicate that 30 to 40 percent of patients with major depression do not respond to first-line antidepressant treatment with drugs such as fluoxetine, upropion, venlafaxine and others. Riluzole, which is approved by the Food and Drug Administration (FDA) for amyotrophic lateral sclerosis (ALS), causes chemical changes in the brain that may also have antidepressant properties.
Patients between 18 and 70 years of age with major depressive disorder without psychotic features may be eligible for this 2-stage 7-week study. Candidates will be screened with a medical history and physical examination, including an electrocardiogram (EKG), blood and urine tests, and a psychiatric evaluation. A
blood or urine sample will be tested for illegal drugs.Women of childbearing potential will have a pregnancy test.
Participants will complete stage 1 of the study, which lasts 1 week, and may then continue with stage 2 for an additional 6 weeks. At the start of the study, patients will be tapered off all psychiatric medicines and will begin treatment with a placebo (a sugar pill formulated to look like the active drug). At some point, they will be switched from placebo to riluzole. In addition, participants will undergo the following procedures:
- Physical examination and electrocardiograms (EKG) at the beginning and end of the study, with vital signs (temperature, blood pressure and heart rate) checked daily
- Weekly 1-hour interviews consisting of psychiatric and psychomotor rating scales to assess treatment response
- Weekly blood tests to measure blood levels of riluzole and evaluate drug side effects
At the end of the study, participants' psychiatric status will be reassessed and appropriate long-term psychiatric treatment arranged.
Patients, ages 18 to 70 with a diagnosis of major depression without psychotic features, will in this pilot study (single arm, single blind) receive riluzole (50-200 mg/day) for a period of 6 weeks. Acute efficacy will be determined by demonstrating a greater response rate using specified criteria.
Approximately 25 patients will enter the study to obtain 22 subjects who complete the 6 weeks of acute riluzole treatment. Therefore, if 7/22 patients or greater have greater than 50% improvement on the primary efficacy measure, then based on statistically guidelines from the Optimal Two Stage Design for Clinical Trials, a controlled trial would be indicated to scientifically confirm the signal observed in the single arm trial.
Detailed description
Major affective disorders are common, severe, chronic and often life-threatening illnesses. Major depression contributes to significant morbidity and mortality. Impairment in physical and social functioning resulting from depression can be just as severe as other chronic medical illnesses. Suicide is the cause of death in 10-20% of individuals with either bipolar or recurrent depressive disorders.
Despite the availability of a wide range of antidepressant drugs, clinical trials indicate that 30% to 40% of patients with major depression fail to respond to first-line antidepressant treatment, despite adequate dosage, duration, and compliance. Thus, there is a clear need to develop novel and improved therapeutics for unipolar and bipolar depression. Recent preclinical studies suggest that antidepressants may exert delayed indirect effects on the glutamatergic system. Furthermore, a growing body of data suggests that mood disorders are associated with regional volumetric reductions, and cell loss and atrophy. It is thus noteworthy that lamotrigine, which, among other effects reduces glutamate release, has antidepressant effects, and a pilot study has suggested that NMDA antagonists may have antidepressant effects. Together, this data suggests that the glutamatergic system may play a role in the pathophysiology and treatment of depression, and that agents, which more directly reduce glutamatergic neurotransmission, may represent a novel class of antidepressants.
Riluzole, an agent that is Food and Drug Administration-approved for Amyotrophic Lateral Sclerosis has significant antiglutamatergic and neuroprotective properties, may prove to have antidepressant properties in depressed patients. In this study, we propose to investigate the potential antidepressant efficacy of riluzole, an agent which reduces glutamatergic throughput via inhibition of its release, which also exerts robus neurotrophic effects.
This is a 6-week single-arm, single-blind study that will examine the efficacy and safety of riluzole in patients with major depression without psychotic features.
The study has two Study Periods. Study Period I is the washout phase that will last 7 days. Study Period II is a monotherapy 6-week acute treatment phase in which the efficacy and tolerability of riluzole is compared to baseline.
Patients, ages 18 to 60 with a diagnosis of major depression without psychotic features, will in this pilot study (single arm, single-blind) receive riluzole (50-200 mg/day) for a period of 6 weeks. Acute efficacy will be determined by demonstrating a greater response rate using specified criteria.
Approximately 25 patients will enter the study to obtain 22 subjects who complete the 6 weeks of acute riluzole treatment. Therefore if 7/22 patients or greater have greater than 50% improvement on the primary efficacy measure, then based on statistically guidelines from the Optimal Two Stage Design for Clinical Trials, a controlled trial would be indicated to scientifically confirm the signal observed in the single arm trial.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female subjects, 18 to 70 years of age will be eligible.
- Female subjects of childbearing potential must be using a medically accepted means of contraception.
- Each subject must have a level of understanding sufficient to agree to all required tests and examinations.
- Each subject must understand the nature of the study and must sign an informed consent document.
- Subjects must fulfill the criteria for major depression, recurrent without psychotic features as defined in DSM-IV (296.32, 296.33) based on clinical assessment and confirmed by structured diagnostic interview SCID-P.
Key exclusion criteria (15 listed)
- Presence of psychotic features.
- Participate in a clinical trial of another investigational drug within 1 month (30 days) prior to study entry (Visit 1).
- Female subjects who are either pregnant or nursing.
- Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
- Subjects with uncorrected hypothyroidism or hyperthyroidism.
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 |
|---|---|---|
| riluzole | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 8784132Aronowski J, Strong R, Grotta JC. Combined neuroprotection and reperfusion therapy for stroke. Effect of lubeluzole and diaspirin cross-linked hemoglobin in experimental focal ischemia. Stroke. 1996 Sep;27(9):1571-6; discussion 1576-7. doi: 10.1161/01.str.27.9.1571.
- Background: PubMed 8214185Altamura CA, Mauri MC, Ferrara A, Moro AR, D'Andrea G, Zamberlan F. Plasma and platelet excitatory amino acids in psychiatric disorders. Am J Psychiatry. 1993 Nov;150(11):1731-3. doi: 10.1176/ajp.150.11.1731.
- Background: PubMed 7631357Abe K, Aoki M, Kawagoe J, Yoshida T, Hattori A, Kogure K, Itoyama Y. Ischemic delayed neuronal death. A mitochondrial hypothesis. Stroke. 1995 Aug;26(8):1478-89. doi: 10.1161/01.str.26.8.1478.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing riluzole in people with Depression, run by National Institute of Mental Health (NIMH) 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 10 inclusion and 15 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 4 Mar 2008. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00026052, 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 4 Mar 2008.