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Mild Cognitive ImpairmentPhase 2/3NCT01876823

Memantine Plus Es-citalopram in Elderly Depressed Patients With Cognitive Impairment

A Phase 2/3 study testing es-citalopram and Memantine in people with Mild Cognitive Impairment and Major Depressive Disorder, run by New York State Psychiatric Institute 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

Alzheimer's disease (AD), the most common dementing disorder of later life, is a major cause of disability and death in the elderly. Although a number of theoretical causes exist, the etiology of AD is still unknown. Consequently, the focus of treatments has been palliative, designed to ameliorate AD symptoms. Read more about this study

Who is it for?
Ages 50 to 90 years
What is being tested?
es-citalopram and Memantine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteUnited States
Study dates
Apr 2006to Mar 2010
Phase
Phase 2/3
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 50 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Of either sex, age greater than 49 years old
  • Meets criteria for both "depression" and "cognitive impairment".
  • Study Criteria for "depression":
  • Patients who meet DSM-IV criteria for Major Depression, Dysthymic Disorder, or Dysthymia symptoms criteria of minimum 6 month duration (not the 2 year DSM-IV criteria). ii. 24-item HAM-D greater than 13; and iii. Clinical Global Impression (CGI) for severity of Depression greater than 2 (absolute score at least mild to moderate depression on a 7-point scale)
  • Study Criteria for "cognitive deficit":
  • Subjective memory complaint ii.Mini Mental Status Exam (MMSE) greater than 24; and at least one of a, b, or c:
Show all 12Show fewer
  • less than 3 on MMSE 5 min delay on recall
  • scores on 2 neuropsychological tests greater than 1 Standard Deviation (SD) below standardized norms, or
  • score on 1 neuropsychological tests greater than 2 SD below standardized norms.
  • Neuropsychological tests for inclusion criteria (subset of larger battery):
  • Selective Reminding Test with delay Wechsler Memory Scale (WMS): Visual Reproduction - with delay, % savings from immed to delay Controlled Oral Word Association Test Trails B Digit symbol subtest of Wechsler Adult Intelligence Scale (WAIS)-III Continuous Performance Test iii. CGI for severity of Cognitive deficit greater than 2 (absolute score on a 7-point scale:1=no deficit to 7=severe deficit). iv. Clinical Dementia Rating (CDR) = 0 or 0.5
  • Willing and capable of giving informed consent

Who cannot join

  • Meets Criteria for dementia (DSM-IV) or probable Alzheimer's disease by National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria (NINCDS-ADRDA criteria)
  • Meets criteria for:
  • schizophrenia
  • alcohol or substance dependence or abuse within the last 6 months.
  • Suicidal attempt in last 6 months or current suicidal intent.
  • Patients currently on an effective antidepressant medication
Show all 11Show fewer
  • Use of cholinesterase inhibitors in the last year.
  • Neurological disease including stroke, epilepsy, or other neurodegenerative disorders.
  • An acute, severe or unstable medical condition such as metastatic or active cancer, hepatic disease, or primary renal disease requiring dialysis.
  • Patients who can not tolerate being tapered off antidepressant medication (i.e. greater than a 25% incr. in baseline HAM-D) or has a history indicating patient is unlikely to tolerate psychotropic washout.
  • Patient with a history of non-response to Citalopram or es-citalopram

Trial locations and contacts

1 site in 1 country.

United States1 site

  • New York State Psychiatric Institute

    New York, New York, 10032

Other trials in United States

About this study

Official title: Effects of Combined Memantine (Namenda) Plus Escitalopram (Lexapro) Treatment in Elderly Depressed Patients With Cognitive Impairment

Alzheimer's disease (AD), the most common dementing disorder of later life, is a major cause of disability and death in the elderly. Although a number of theoretical causes exist, the etiology of AD is still unknown. Consequently, the focus of treatments has been palliative, designed to ameliorate AD symptoms. Recent efforts, however, have revealed some surprising data suggesting that cholinesterase inhibitors (AchEIs), used over the last decade, and recently released memantine (an N-methyl-D-aspartate (NMDA) receptor antagonist), may confer protection to neurons. Thus, they may offer a slowing of cognitive decline and/or improvement in behavioral symptoms associated with memory impairment.

Over the last decade, it has been well documented that mild cognitive impairment (MCI) increases the risk of conversion to AD and that coincident depression and MCI (Dep-MCI) further increases the risk 2 to 3 fold. The primary focus of this line of investigation is to treat the very high risk to dement patient population with Dep-MCI, before they develop AD, in the hopes of delaying AD onset.

Memantine had not been studied in DEP-MCI patients. Since treatment of these patients with combined antidepressant and AChEIs has been associated with cognitive improvement in pilot studies, we explore whether treatment of DEP-MCI with memantine in addition to antidepressant treatment would benefit cognitive performance and lead to a low rate of conversion to dementia. We evaluate the cognitive and antidepressant benefit of combined open-label es-citalopram and memantine treatment over 48 weeks in a DEP-CI sample.

Read the detailed description

The study is conducted in a sample of 35 elderly (50-90 years old) outpatients who meet study inclusion criteria for depression (DEP) (DSM-IV criteria for major depression, dysthymic disorder, or depression NOS) and mild cognitive impairment (MCI; e.g. operationally defined as between "normal" and "dementia"), i.e., Dep-MCI. The research plan includes: i) Obtaining a baseline psychiatric and neuropsychological test profile, ii) If currently on an ineffective antidepressant, having a one week washout (3 weeks for fluoxetine), iii) A treatment trial beginning with a two-week es-citalopram lead-in period. At two weeks, memantine (Namenda) is added starting at 5 mg/day and increased until the maximum dose of 20 mg/day is reached by six weeks. The study psychiatrist administers: the 24-item Hamilton Depression Rating Scale (HAM-D); the Clinical Global Impression (CGI, 1-7 scale) initial severity and subsequent change ratings separately for depression, cognition, and overall clinical status; the Treatment Emergent Symptom Scale (TESS) for somatic side effects. A trained technician administers the neuropsychological battery at baseline, 12, 24 and 48 weeks. If the patient is an antidepressant non-responder during the first 12-weeks, the es-citalopram is changed to an alternative antidepressant, as clinically indicated by the treating psychiatrist. The patient remains on the memantine for the entire 48-weeks, irrespective of antidepressant response.

This will tell us about the efficacy and tolerability of es-citalopram+memantine on both cognitive and depressive symptoms in Dep-MCI patients and will potentially have broader public health implications because Dep-MCI is a wide-spread clinical problem where management needs to be improved.

Being tested
es-citalopram, Memantine
Keywords
Memory Decline, Depression, Elderly, Antidepressants, Treatment, memantine
Medical subject headings
Cognitive Dysfunction, Depressive Disorder, Major, Alzheimer Disease, Depression

What participants receive

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

  • es-citalopramDrug

    Also called Lexapro

    es-citalopram 10mg/day will be given for the first week, and 20mg/day starting at week 2.

  • MemantineDrug

    Also called Namenda

    After two weeks on Lexapro, Memantine 5mg will be added. The dose will increase to 10mg for the second week and will be increased at a rate of 5mg per week. Memantine dosage will not exceed 20mg.

Study groups in NCT01876823
Study groupRoleWhat they receive
es-citalopram and Memantine TreatmentExperimentalconcurrent es-citalopram plus memantine were administered for 48 weeks.
Receives: Drug: es-citalopram; Drug: Memantine

What is being measured

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

  1. Change in Selective Reminding Test - Total Immediate Recall (SRT-IR)

    Change in Selective Reminding Test-Total Immediate Recall (SRT-IR) scores from baseline to Week 48: Measures word recall (maximum 12 words per trial, across 6 trials). Maximum total recall score across 6 trials is 72; minimum recall is 0 across 6 trials. The higher the raw score, the better the patient did at recalling the target words. The unit of measure is the raw score, or the sum of the number of words recalled across all 6 trials.

    Measured: baseline, 48 weeks

Secondary outcomes (4)

  1. Change in Wechsler Memory Scale-III (WMS-III)

    Change in Wechsler Memory Scale-III scores from baseline to Week 48: The WMS-III Visual Reproduction sub-test was used to measure visual working memory and delayed memory. Patients were shown pictures of four drawings and were asked to reproduce them from memory immediately after seeing them, and 25 minutes after seeing them. The four scores are summed and the greater the total raw score, the better the patient did on the assessment. The maximum raw score for this test is a 41 on both the immediate and delayed portions (the overall range is 0-82 points). The change score is calculated using the total scores of both the immediate and delayed portions.

    Measured: Baseline, Week 48

  2. Change in Selective Reminding Test - Delayed Recall (SRT-DR)

    Change in Selective Reminding Test-Delayed Recall scores from baseline to Week 48: SRT Delay is administered 15 minutes after the immediate recall portion. Patients are asked to remember as many of the words as they can from the 6 trials. Maximum raw score is a 12 for free recall. If a patient is unable to recall a word, they are given a chance to recognize it among three incorrect word choices. Maximum raw score for recognition is 12. The greater the score on the delayed recall portion, the better the patient does on the assessment.

    Measured: Baseline, Week 48

  3. Change in Trails B

    Change from baseline to Week 48 on Trails B: Measures attention and executive function. It asks patients to connect numbers and letters in numerical to alphabetical order from (1-13 and A-L) as fast as they can. Patients are timed; the longer it takes for the patient to connect the numbers and letters, the worse their score. Unit of measure is in seconds. The amount of errors that the patient makes during trails is also recorded.

    Measured: Baseline, Week 48

  4. Change in Trails A

    Change in Trails A scores from baseline to Week 48: Measures attention and executive function. It asks patients to connect numbers from 1-25 in numerical order as fast as they can. Patients are timed; the longer it takes for the patient to connect the numbers, the worse their score. Unit of measure is in seconds. The amount of errors that the patient makes during trails is also recorded.

    Measured: Baseline, Week 48

Timeline

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

  1. First posted13 Jun 2013 (estimated)
  2. Study startApr 2006
  3. Primary completionMar 2010
  4. Study completionMar 2010

Resources

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 2/3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01876823
Sponsor's protocol ID
6277R
Status last verified
Sep 2013
First submitted
5 Jun 2013
Last updated
24 Oct 2014
Data monitoring committee
No

Publications

  • Alexopoulos GS, Meyers BS, Young RC, Mattis S, Kakuma T. The course of geriatric depression with "reversible dementia": a controlled study. Am J Psychiatry. 1993 Nov;150(11):1693-9. doi: 10.1176/ajp.150.11.1693.

    PubMed 8105707

  • Atri A, Shaughnessy LW, Locascio JJ, Growdon JH. Long-term course and effectiveness of combination therapy in Alzheimer disease. Alzheimer Dis Assoc Disord. 2008 Jul-Sep;22(3):209-21. doi: 10.1097/WAD.0b013e31816653bc.

    PubMed 18580597

  • Bakchine S, Loft H. Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study. J Alzheimers Dis. 2008 Feb;13(1):97-107. doi: 10.3233/jad-2008-13110.

    PubMed 18334761

  • Barnes DE, Yaffe K, Byers AL, McCormick M, Schaefer C, Whitmer RA. Midlife vs late-life depressive symptoms and risk of dementia: differential effects for Alzheimer disease and vascular dementia. Arch Gen Psychiatry. 2012 May;69(5):493-8. doi: 10.1001/archgenpsychiatry.2011.1481.

    PubMed 22566581

  • Bassuk SS, Berkman LF, Wypij D. Depressive symptomatology and incident cognitive decline in an elderly community sample. Arch Gen Psychiatry. 1998 Dec;55(12):1073-81. doi: 10.1001/archpsyc.55.12.1073.

    PubMed 9862549

  • Boyle PA, Wilson RS, Aggarwal NT, Tang Y, Bennett DA. Mild cognitive impairment: risk of Alzheimer disease and rate of cognitive decline. Neurology. 2006 Aug 8;67(3):441-5. doi: 10.1212/01.wnl.0000228244.10416.20.

    PubMed 16894105

  • Burt DB, Zembar MJ, Niederehe G. Depression and memory impairment: a meta-analysis of the association, its pattern, and specificity. Psychol Bull. 1995 Mar;117(2):285-305. doi: 10.1037/0033-2909.117.2.285.

    PubMed 7724692

  • Charney DS, Reynolds CF 3rd, Lewis L, Lebowitz BD, Sunderland T, Alexopoulos GS, Blazer DG, Katz IR, Meyers BS, Arean PA, Borson S, Brown C, Bruce ML, Callahan CM, Charlson ME, Conwell Y, Cuthbert BN, Devanand DP, Gibson MJ, Gottlieb GL, Krishnan KR, Laden SK, Lyketsos CG, Mulsant BH, Niederehe G, Olin JT, Oslin DW, Pearson J, Persky T, Pollock BG, Raetzman S, Reynolds M, Salzman C, Schulz R, Schwenk TL, Scolnick E, Unutzer J, Weissman MM, Young RC; Depression and Bipolar Support Alliance. Depression and Bipolar Support Alliance consensus statement on the unmet needs in diagnosis and treatment of mood disorders in late life. Arch Gen Psychiatry. 2003 Jul;60(7):664-72. doi: 10.1001/archpsyc.60.7.664.

    PubMed 12860770

  • Chen X, Magnotta VA, Duff K, Boles Ponto LL, Schultz SK. Donepezil effects on cerebral blood flow in older adults with mild cognitive deficits. J Neuropsychiatry Clin Neurosci. 2006 Spring;18(2):178-85. doi: 10.1176/jnp.2006.18.2.178.

    PubMed 16720794

  • Culang ME, Sneed JR, Keilp JG, Rutherford BR, Pelton GH, Devanand DP, Roose SP. Change in cognitive functioning following acute antidepressant treatment in late-life depression. Am J Geriatr Psychiatry. 2009 Oct;17(10):881-8. doi: 10.1097/jgp.0b013e3181b4bf4a.

    PubMed 19916207

  • Devanand DP, Liu X, Tabert MH, Pradhaban G, Cuasay K, Bell K, de Leon MJ, Doty RL, Stern Y, Pelton GH. Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer's disease. Biol Psychiatry. 2008 Nov 15;64(10):871-9. doi: 10.1016/j.biopsych.2008.06.020. Epub 2008 Aug 23.

    PubMed 18723162

  • Devanand DP, Pelton GH, Marston K, Camacho Y, Roose SP, Stern Y, Sackeim HA. Sertraline treatment of elderly patients with depression and cognitive impairment. Int J Geriatr Psychiatry. 2003 Feb;18(2):123-30. doi: 10.1002/gps.802.

    PubMed 12571820

  • Devanand DP, Sano M, Tang MX, Taylor S, Gurland BJ, Wilder D, Stern Y, Mayeux R. Depressed mood and the incidence of Alzheimer's disease in the elderly living in the community. Arch Gen Psychiatry. 1996 Feb;53(2):175-82. doi: 10.1001/archpsyc.1996.01830020093011.

    PubMed 8629893

  • Doody RS, Ferris SH, Salloway S, Sun Y, Goldman R, Watkins WE, Xu Y, Murthy AK. Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial. Neurology. 2009 May 5;72(18):1555-61. doi: 10.1212/01.wnl.0000344650.95823.03. Epub 2009 Jan 28.

    PubMed 19176895

  • Farrimond LE, Roberts E, McShane R. Memantine and cholinesterase inhibitor combination therapy for Alzheimer's disease: a systematic review. BMJ Open. 2012 Jun 11;2(3):e000917. doi: 10.1136/bmjopen-2012-000917. Print 2012.

    PubMed 22689908

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing es-citalopram and Memantine in people with Mild Cognitive Impairment and Major Depressive Disorder, run by New York State Psychiatric Institute 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 12 inclusion and 11 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 24 Oct 2014. 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 combined 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.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 24 Oct 2014). 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?

Change in Selective Reminding Test - Total Immediate Recall (SRT-IR) (time frame: baseline, 48 weeks). 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 NCT01876823, which also lists 49 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 24 Oct 2014.

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