Trial Outcomes & Findings for Memantine Plus Es-citalopram in Elderly Depressed Patients With Cognitive Impairment (NCT NCT01876823)
NCT ID: NCT01876823
Last Updated: 2014-10-24
Results Overview
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.
COMPLETED
PHASE2/PHASE3
60 participants
baseline, 48 weeks
2014-10-24
Participant Flow
35 depressed and cognitively impaired patients were recruited from the Late Life Depression and Memory Disorders Clinic at Columbia University Medical Center.
Any patients who were diagnosed with schizophrenia, psychoses, bipolar disorder, or alcohol/substance dependence (within the last 6 months) were excluded from participating in the study. Patients already on an effective anti-depressant, non-responders to citalopram/es-citalopram, and those on cholinesterase inhibitors/memantine were also excluded.
Participant milestones
| Measure |
Es-citalopram and Memantine Treatment
This group received concurrent es-citalopram plus memantine treatment for 48 weeks. Patients ranged in age from 50-90 years old. Es-citalopram treatment began at 10mg per day for two weeks and was increased to 20mg per day for the 48 week duration. If a patient had an inadequate response to the antidepressant on two consecutive visits, the study physician used an alternative. At two weeks into the study, the patients were started on memantine 5mg, and the maximum dose of 20mg was reached by the six week point.
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|---|---|
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Overall Study
STARTED
|
35
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Overall Study
COMPLETED
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26
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Overall Study
NOT COMPLETED
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9
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Reasons for withdrawal
| Measure |
Es-citalopram and Memantine Treatment
This group received concurrent es-citalopram plus memantine treatment for 48 weeks. Patients ranged in age from 50-90 years old. Es-citalopram treatment began at 10mg per day for two weeks and was increased to 20mg per day for the 48 week duration. If a patient had an inadequate response to the antidepressant on two consecutive visits, the study physician used an alternative. At two weeks into the study, the patients were started on memantine 5mg, and the maximum dose of 20mg was reached by the six week point.
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|---|---|
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Overall Study
Withdrawal by Subject
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5
|
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Overall Study
Physician Decision
|
2
|
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Overall Study
Patients moved
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2
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Baseline Characteristics
Memantine Plus Es-citalopram in Elderly Depressed Patients With Cognitive Impairment
Baseline characteristics by cohort
| Measure |
Es-citalopram and Memantine Treatment
n=35 Participants
concurrent es-citalopram plus memantine were administered for 48 weeks.
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|---|---|
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Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
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Age, Categorical
Between 18 and 65 years
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0 Participants
n=5 Participants
|
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Age, Categorical
>=65 years
|
35 Participants
n=5 Participants
|
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Age, Continuous
|
65.3 years
STANDARD_DEVIATION 8.9 • n=5 Participants
|
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Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
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Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
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28 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
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Region of Enrollment
United States
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35 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: baseline, 48 weeksPopulation: Analysis was intent to treat.
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.
Outcome measures
| Measure |
Es-citalopram and Memantine Treatment
n=35 Participants
concurrent es-citalopram plus memantine were administered for 48 weeks.
|
|---|---|
|
Change in Selective Reminding Test - Total Immediate Recall (SRT-IR)
|
7.5 units on a scale
Standard Deviation 15
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: Analysis was intent to treat.
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.
Outcome measures
| Measure |
Es-citalopram and Memantine Treatment
n=35 Participants
concurrent es-citalopram plus memantine were administered for 48 weeks.
|
|---|---|
|
Change in Wechsler Memory Scale-III (WMS-III)
|
9.9 units on a scale
Standard Deviation 32.8
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SECONDARY outcome
Timeframe: Baseline, Week 48Population: Analysis was intent to treat.
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.
Outcome measures
| Measure |
Es-citalopram and Memantine Treatment
n=35 Participants
concurrent es-citalopram plus memantine were administered for 48 weeks.
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|---|---|
|
Change in Selective Reminding Test - Delayed Recall (SRT-DR)
|
1.2 units on a scale
Standard Deviation 3.9
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SECONDARY outcome
Timeframe: Baseline, Week 48Population: Analysis was intent to treat.
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.
Outcome measures
| Measure |
Es-citalopram and Memantine Treatment
n=35 Participants
concurrent es-citalopram plus memantine were administered for 48 weeks.
|
|---|---|
|
Change in Trails B
|
-36.3 seconds
Standard Deviation 74.5
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SECONDARY outcome
Timeframe: Baseline, Week 48Population: Analysis was intent to treat.
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.
Outcome measures
| Measure |
Es-citalopram and Memantine Treatment
n=35 Participants
concurrent es-citalopram plus memantine were administered for 48 weeks.
|
|---|---|
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Change in Trails A
|
1.9 seconds
Standard Deviation 41.2
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OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 48Population: Analysis was intent to treat.
Change in 24-item Hamilton Rating Scale for Depression (HAMD) scores from baseline to Week 48: HAMD measures depression severity based on a series of 24 items items. The range of HAMD total score is 0-74; 0 indicates no depressive symptoms and a maximum HAMD score is a 74, where the greater the score indicates more significant psychopathology. In this study, moderate to severe depression is considered a HAMD-24 greater than 14.
Outcome measures
| Measure |
Es-citalopram and Memantine Treatment
n=35 Participants
concurrent es-citalopram plus memantine were administered for 48 weeks.
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|---|---|
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Change in 24-item HAMD
|
-15.2 scores on a scale
Standard Deviation 4.4
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OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 48Population: Analysis was intent to treat.
Somatic side effect rating scale which includes 26 common somatic side effects associated with previous medication clinical trials; rated by the study physician. Factors were dichotomized to "yes" or "no" responses on this scale, which equated to the symptom being either present or not present. "Yes" and "no" responses were given a value of 0 (no) or 1 (yes). Responses from the entire group were calculated and the mean at baseline and the last visit is reported below.
Outcome measures
| Measure |
Es-citalopram and Memantine Treatment
n=35 Participants
concurrent es-citalopram plus memantine were administered for 48 weeks.
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|---|---|
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Change in Treatment Emergent Side Effects (TESS)
Treatment Emergent Side Effects (Baseline)
|
6.6 units on a scale
Standard Deviation 4.2
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Change in Treatment Emergent Side Effects (TESS)
Treatment Emergent Side Effects (WK 48)
|
3.2 units on a scale
Standard Deviation 2.9
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OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 48Population: Analysis was intent to treat; ANOVA repeated measures. All values of data collected were included, except for those who exited the study early. In these cases, their last observation was carried forward (LOC).
The CGI Depression Change follows a seven-point likert scale. Compared to the patient's condition at baseline in the study \[prior to medication initiation\], the patient's condition is rated as: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment. Responses were calculated for the entire group. Mean at final visit has been reported below. Higher mean at baseline indicates a decrease in depression scores.
Outcome measures
| Measure |
Es-citalopram and Memantine Treatment
n=35 Participants
concurrent es-citalopram plus memantine were administered for 48 weeks.
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|---|---|
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Change in Clinical Global Impression - Depression Change
Cognitive Global Impression at Baseline
|
4.1 units on a scale
Standard Deviation 0.5
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Change in Clinical Global Impression - Depression Change
Cognitive Global Impression at Final Visit (WK 48)
|
2.1 units on a scale
Standard Deviation 1.2
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OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 48Population: Analysis was intent to treat; ANOVA repeated measures. All values of data collected were included, except for those who exited the study early. In these cases, their last observation was carried forward (LOC).
The CGI Cognitive Change follows a seven-point likert scale. Compared to the patient's condition at baseline in the study \[prior to medication initiation\], the patient's condition is rated as: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment. Responses from the entire group were calculated. Mean at final visit and baseline is reported below.
Outcome measures
| Measure |
Es-citalopram and Memantine Treatment
n=35 Participants
concurrent es-citalopram plus memantine were administered for 48 weeks.
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|---|---|
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Change in Clinical Global Impression - Cognitive Change
CGI-Cognitive Change (Baseline)
|
3.6 units on a scale
Standard Deviation 0.6
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Change in Clinical Global Impression - Cognitive Change
Clinical Global Impression-Cogntive Change (WK 48)
|
2.7 units on a scale
Standard Deviation 0.9
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OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 48Population: Analysis was intent to treat; ANOVA repeated measures. All values of data collected were included, except for those who exited the study early. In these cases, their last observation was carried forward (LOC).
The CDR is a numeric rating scale that is used to quantify the severity of one's cognitive function. The scale goes from 0=normal; 0.5=mild cognitive impairment; 1 to 3=mild to moderate/severe dementia. CDR was used a dichotomous outcome measure (no=0; yes=1).
Outcome measures
| Measure |
Es-citalopram and Memantine Treatment
n=35 Participants
concurrent es-citalopram plus memantine were administered for 48 weeks.
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|---|---|
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Conversion to Dementia Using Clinical Dementia Rating (CDR)
|
1 participants
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Adverse Events
Es-citalopram and Memantine Treatment
Serious adverse events
| Measure |
Es-citalopram and Memantine Treatment
n=35 participants at risk
concurrent es-citalopram plus memantine were administered for 48 weeks.
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|---|---|
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Cardiac disorders
Syncopal Episode
|
2.9%
1/35 • Number of events 1 • From initiation of study until one month after study completion- a total of 13 months.
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Nervous system disorders
Dizziness
|
2.9%
1/35 • Number of events 1 • From initiation of study until one month after study completion- a total of 13 months.
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Other adverse events
| Measure |
Es-citalopram and Memantine Treatment
n=35 participants at risk
concurrent es-citalopram plus memantine were administered for 48 weeks.
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|---|---|
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Nervous system disorders
Headache
|
2.9%
1/35 • Number of events 4 • From initiation of study until one month after study completion- a total of 13 months.
|
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Nervous system disorders
Sedation
|
5.7%
2/35 • Number of events 4 • From initiation of study until one month after study completion- a total of 13 months.
|
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Gastrointestinal disorders
Nausea
|
2.9%
1/35 • Number of events 4 • From initiation of study until one month after study completion- a total of 13 months.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place