Ignite Creation Date:
2025-12-24 @ 12:49 PM
Ignite Modification Date:
2025-12-31 @ 6:34 PM
Study NCT ID:
NCT00040261
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2002-06-22
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Clinical Trial of Memantine for Major Depression
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003863', 'term': 'Depression'}, {'id': 'D003866', 'term': 'Depressive Disorder'}, {'id': 'D003865', 'term': 'Depressive Disorder, Major'}], 'ancestors': [{'id': 'D001526', 'term': 'Behavioral Symptoms'}, {'id': 'D001519', 'term': 'Behavior'}, {'id': 'D019964', 'term': 'Mood Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008559', 'term': 'Memantine'}], 'ancestors': [{'id': 'D000547', 'term': 'Amantadine'}, {'id': 'D000218', 'term': 'Adamantane'}, {'id': 'D001952', 'term': 'Bridged-Ring Compounds'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'primaryPurpose': 'TREATMENT'}, 'enrollmentInfo': {'count': 112}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2002-06'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2005-03', 'completionDateStruct': {'date': '2005-03'}, 'lastUpdateSubmitDate': '2008-03-03', 'studyFirstSubmitDate': '2002-06-22', 'studyFirstSubmitQcDate': '2002-06-22', 'lastUpdatePostDateStruct': {'date': '2008-03-04', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2002-06-24', 'type': 'ESTIMATED'}}, 'conditionsModule': {'keywords': ['Antiglutamatergic', 'Neuroprotective', 'Unipolar Depression', 'Treatment', 'Antidepressant', 'Depression', 'Glutamate', 'Memantine', 'Pathophysiology', 'Positron Emission Tomography', 'Major Depression'], 'conditions': ['Depression']}, 'referencesModule': {'references': [{'pmid': '8214185', 'type': 'BACKGROUND', 'citation': "Altamura 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."}, {'pmid': '10686265', 'type': 'BACKGROUND', 'citation': 'Auer DP, Putz B, Kraft E, Lipinski B, Schill J, Holsboer F. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry. 2000 Feb 15;47(4):305-13. doi: 10.1016/s0006-3223(99)00159-6.'}, {'pmid': '3406051', 'type': 'BACKGROUND', 'citation': 'Ambrozi L, Danielczyk W. Treatment of impaired cerebral function in psychogeriatric patients with memantine--results of a phase II double-blind study. Pharmacopsychiatry. 1988 May;21(3):144-6. doi: 10.1055/s-2007-1014666.'}, {'pmid': '27914292', 'type': 'DERIVED', 'citation': 'Lepow L, Luckenbaugh DA, Park L, Henter ID, Zarate CA Jr. Case series: Antidepressant effects of low-affinity and low-trapping NMDA receptor antagonists did not predict response to ketamine in seven subjects. J Psychiatr Res. 2017 Mar;86:55-57. doi: 10.1016/j.jpsychires.2016.10.023. Epub 2016 Nov 22. No abstract available.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to determine the safety and effectiveness of the drug memantine for treating major depression.\n\nMajor depression is a serious public health concern that contributes to significant morbidity and mortality. Despite the availability of a wide range of antidepressant drugs, a proportion of patients with major depression fail to respond to first-line antidepressant treatment, despite adequate dosage, duration, and compliance. Recent studies suggest that the glutamatergic system may play a role in the pathophysiology and treatment of depression. Memantine and other agents which reduce glutamatergic neurotransmission may represent a novel class of antidepressants.\n\nThe study consists of three phases. In Phase 1, participants will be tapered off all psychiatric medications over a 2-week washout period. In Phase 2, participants will be randomly assigned to receive either memantine or placebo (an inactive pill) three times a day for 8 weeks. Participants who do not respond to the treatment after 8 weeks will be taken off the study and offered standard treatment. Weekly psychiatric evaluations will evaluate treatment response. During Phase 2, participants who respond well to treatment will enter Phase 3, a 16-week continuation phase of either memantine or placebo. Interviews will be conducted every other week in the first month , then monthly thereafter.\n\nParticipants will have a physical examination, neuropsychological tests, and eye blink tests at baseline and at the end of the study. Pulse, blood pressure, and blood samples will be taken throughout the study. Participants will undergo an electrocardiogram as well as positron emission tomography (PET) and magnetic resonance imaging (MRI) scans of the brain.', 'detailedDescription': "Major affective disorders are common, severe, chronic and often a life-threatening illness. 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 recurrent depressive disorders.\n\nDespite 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.\n\nMemantine (Akatinol memantine), an agent that is approved in Germany for dementia syndrome, Parkinson's disease has significant antiglutamatergic and neuroprotective properties, may prove to have antidepressant properties in depressed patients. In this study, we propose to investigate the potential efficacy of memantine, an agent which reduces glutamatergic output via open-channel block of the NMDA receptor-associated ion channel. Most importantly, memantine only blocks the channel during periods of abnormal, excessive activity, and leaves relatively spared normal neurotransmission. This finding is the basis for the minimal side effect profile displayed by memantine.\n\nPatients, ages 18 to 80, with a diagnosis of major depression (without psychotic features), will be randomized to double-blind treatment outpatient study to receive either memantine (5-20mg/day) or placebo for a period of 8 weeks. Following this acute period, patients who fully respond could enter a 16-week continuation phase. Acute efficacy will be determined by demonstrating a greater response rate using specified criteria. Approximately 112 patients with acute major depression will be enrolled in the study."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'healthyVolunteers': False, 'eligibilityCriteria': 'INCLUSION CRITERIA:\n\nSubjects may be included in the study only if they meet all of the following criteria:\n\nMale or female subjects, 18 to 80 years of age.\n\nFemale subjects of childbearing potential must be using a medically accepted means of contraception.\n\nEach subject must have a level of understanding sufficient to agree to all tests and examinations required by the protocol.\n\nSubjects must be considered reliable.\n\nEach subject must understand the nature of the study and must sign an informed consent document.\n\nSubjects must fulfill the criteria for major depression, recurrent without psychotic features as defined in DSM-IV based on clinical assessment and confirmed by structured diagnostic interview SCID-P.\n\nSubjects must have an initial score at Visit 1 and Visit 2 of at least 22 on the MADRS.\n\nSubjects must not have a decrease in the total score of MADRS of greater than 20 % during washout (between Visits 1 and 2).\n\nCurrent major depressive episode of at least 4 weeks duration.\n\nEXCLUSION CRITERIA:\n\nSubjects will be excluded from the study for any of the following reasons:\n\nLack of response to more than 2 antidepressants (adequate dose and duration).\n\nParticipation in a clinical trial of another investigational drug within 1 month (30 days) prior to study entry (Visit 1).\n\nFemale subjects who are either pregnant or nursing.\n\nSerious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.\n\nSubjects with uncorrected hypothyroidism or hyperthyroidism.\n\nSubjects with one or more seizures without a clear and resolved etiology.\n\nDocumented history of hypersensitivity or intolerance to amantadine or prior treatment with memantine.\n\nDSM-IV substance abuse or dependence (except nicotine and caffeine) within the past 90 days.\n\nTreatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections prior to Visit 2.\n\nTreatment with a reversible monoamine oxidase inhibitor, guanethidine, or guanadrel within 1 week prior to Visit 2.\n\nTreatment with fluoxetine within 6 weeks prior to Visit 2.\n\nTreatment with any other concomitant medication with primarily CNS activity.\n\nTreatment with clozapine within 4 weeks prior to Visit 2.\n\nTreatment with amitriptyline (elavil) within 4 weeks prior to Visit 2 since amitriptyline and similar TCAs may manifest a mild NMDA receptor antagonism, as demonstrated in electrophysiological studies.\n\nTreatment with the anticonvulsants carbamazepine (tegretol, carbatrol, tegretol XR and similar derivatives), gabapentin (neurontin) or felbamate (felbatol) within 4 weeks prior to Visit 2 because these drugs may interfere with NMDA receptor function.\n\nTreatment with electroconvulsive therapy (ECT) within 3 months (90 days) prior to Visit 2.\n\nCurrent diagnosis of schizophrenia or other psychotic or bipolar disorder as defined in the DSM-IV.\n\nJudged clinically to be at serious suicidal risk.'}, 'identificationModule': {'nctId': 'NCT00040261', 'briefTitle': 'Clinical Trial of Memantine for Major Depression', 'organization': {'class': 'NIH', 'fullName': 'National Institutes of Health Clinical Center (CC)'}, 'officialTitle': 'An Investigation of the Antidepressant Efficacy of Memantine, an NMDA Antagonist With Neurotrophic Properties in Major Depression', 'orgStudyIdInfo': {'id': '020231'}, 'secondaryIdInfos': [{'id': '02-M-0231'}]}, 'armsInterventionsModule': {'interventions': [{'name': 'Memantine HCL', 'type': 'DRUG'}]}, 'contactsLocationsModule': {'locations': [{'zip': '20892', 'city': 'Bethesda', 'state': 'Maryland', 'country': 'United States', 'facility': 'National Institute of Mental Health (NIMH)', 'geoPoint': {'lat': 38.98067, 'lon': -77.10026}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Institute of Mental Health (NIMH)', 'class': 'NIH'}}}}