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Major Depressive DisorderPhase 3FOCUSNCT01422213

Efficacy Study of Vortioxetine on Cognitive Dysfunction in Adult Patients With Major Depressive Disorder

A Phase 3 study testing Vortioxetine (Lu AA21004) in people with Major Depressive Disorder, run by H. Lundbeck A/S.

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

Major Depressive Disorder (MDD) is a severe and common psychiatric disorder. Although MDD primarily involves mood disturbances, patients also usually present alterations in cognitive function (attention, memory, executive functioning and psychomotor speed). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Major Depressive Disorder
What is being tested?
Vortioxetine (Lu AA21004)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
598 participants
Where
No sites listed yet
Study dates
Dec 2011to May 2013
Phase
Phase 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 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The patient is an inpatient in a psychiatric hospital or an outpatient at a psychiatric setting at the time of the study entry.
  • The patient is diagnosed with recurrent MDD according to DSM-IV-TR™ criteria (classification code 296.3x). The current Major Depressive Episode (MDE) should be confirmed using the Mini International Neuropsychiatric Interview (MINI).
  • The patient has received prescribed treatment for a previous episode of depression.
  • The patient has a MADRS total score ≥26.
  • The reported duration of the current MDE is at least 3 months.

Who cannot join

  • The patient has a score ≥70 on the DSST (number of correct symbols), or ≥42 on the RAVLT (learning) or ≥14 on the RAVLT (memory) at the Baseline Visit.
  • The patient has any current Axis I disorder (DSM-IV-TR™ criteria) other than MDD, confirmed using the MINI.
  • The patient has a current diagnosis or history of manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features.
  • The patient suffers from personality disorders, mental retardation, pervasive development disorder, attention-deficit/hyperactivity disorder, organic mental disorders, or mental disorders due to a general medical condition (DSM-IV-TR™ criteria).
  • The patient has physical, cognitive, or language impairment of such severity as to adversely affect the validity of the data derived from the neuropsychological tests.
  • The patient is diagnosed with reading disability (dyslexia).
Show all 32Show fewer
  • The patient is at significant risk of suicide or has a score ≥5 on Item 10 (suicidal thoughts) of the MADRS, or has attempted suicide <6 months prior to the Screening Visit.
  • The patient has received electroconvulsive therapy <6 months prior to the Screening Visit.
  • The current depressive symptoms are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each at the recommended dose.
  • The patient has a history of moderate or severe head trauma (for example, loss of consciousness for more than 1 hour) or other neurological disorders or systemic medical diseases that are, in the opinion of the investigator, likely to affect central nervous system functioning.
  • The patient has a history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin, that has not been in remission for >5 years prior to the first drug dose.
  • The patient has a clinically significant unstable illness, for example:
  • cardiovascular disease
  • seizure disorder or encephalopathy
  • congestive heart failure
  • cardiac hypertrophy
  • arrhythmia
  • bradycardia (pulse <50 bpm)
  • respiratory disease
  • hepatic impairment or renal insufficiency
  • metabolic disorder
  • endocrinological disorder
  • gastrointestinal disorder
  • haematological disorder
  • infectious disorder
  • any clinically significant immunological condition
  • dermatological disorder
  • venereal disease
  • The patient has, at the Screening Visit, an abnormal ECG that is, in the investigator's opinion, clinically significant.
  • The patient is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason.
  • The patient has previously been exposed to Vortioxetine.
  • Other protocol-defined inclusion and exclusion criteria may apply.

About this study

Official title: Randomised, Double-blind, Parallel-group, Placebo-controlled, Fixed Dose Study on the Efficacy of [Vortioxetine] Lu AA21004 on Cognitive Dysfunction in Adult Patients With Major Depressive Disorder (MDD)

Major Depressive Disorder (MDD) is a severe and common psychiatric disorder. Although MDD primarily involves mood disturbances, patients also usually present alterations in cognitive function (attention, memory, executive functioning and psychomotor speed). Even though antidepressants are suggested in the literature to potentially improve cognitive dysfunction in patients with MDD to some degree, there is a lack of adequate and well-controlled studies to investigate this effect. This study will evaluate the efficacy, safety and tolerability of a new antidepressant Vortioxetine versus placebo on cognitive dysfunction in adult patients with MDD.

Being tested
Placebo, Vortioxetine (Lu AA21004)
Keywords
MDD, Cognitive dysfunction
Medical subject headings
Depressive Disorder, Major, Cognitive Dysfunction

What participants receive

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

  • PlaceboDrug

    capsules; daily; orally

  • Vortioxetine (Lu AA21004)Drug

    Also called Brintellix

    encapsulated tablets; daily; orally

  • Vortioxetine (Lu AA21004)Drug

    Also called Brintellix

    encapsulated tablets; daily; orally

Study groups in NCT01422213
Study groupRoleWhat they receive
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo
Vortioxetine 10 mgExperimentalNot described
Receives: Drug: Vortioxetine (Lu AA21004)
Vortioxetine 20 mgExperimentalNot described
Receives: Drug: Vortioxetine (Lu AA21004)

What is being measured

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

  1. Change From Baseline to Week 8 in DSST (Number of Correct Symbols) and RAVLT (Acquisition and Delayed Recall) Using the Composite Z-score Defined as the Weighted Sum of the Individual Patient Z-scores

    DSST assesses psychomotor speed of performance requiring visual perception, spatial decision-making, and motor skills. It consists of 133 digits and requires the patient to substitute each digit with a simple symbol in a 90-s period. Each correct symbol is counted, and the total score ranges from 0 (< normal functioning) to 133 (> normal functioning).

    RAVLT assesses verbal learning and memory, including immediate memory, efficiency of learning, retroactive and proactive interference effects, and encoding versus retrieval. It consists of a number of tasks, including immediate recall and delayed recall. The number of words correctly recalled on each task is recorded.

    The scores are standardized by subtracting the overall mean change from baseline from the individual change from baseline and dividing by the standard deviation estimate of the change from baseline. The 2 tests, DSST and RAVLT are each assigned a weight of 0.5, the 2 subtests of RAVLT are each assigned a weight of 0.25.

    Measured: Baseline and Week 8

Secondary outcomes (17)
  1. Change From Baseline to Week 8 in DSST (Number of Correct Symbols)

    Digit Symbol Substitution Test (DSST) is a cognitive test designed to assess psychomotor speed of performance requiring visual perception, spatial decision-making, and motor skills. It consists of 133 digits and requires the patient to substitute each digit with a simple symbol in a 90-second period. Each correct symbol is counted, and the total score ranges from 0 (less than normal functioning) to 133 (greater than normal functioning)." as a description of DSST.

    Measured: Baseline and Week 8

  2. Change From Baseline to Week 8 in RAVLT (Acquisition)

    Rey Auditory Verbal Learning Task (RAVLT) is a cognitive test designed to assess verbal learning and memory, including immediate memory, efficiency of learning, retroactive and proactive interference effects, and encoding versus retrieval. It consists of a number of tasks, including immediate recall and delayed recall. The number of words correctly recalled on each task is recorded.

    Measured: Baseline and Week 8

  3. Change From Baseline to Week 8 in RAVLT (Delayed Recall)

    Rey Auditory Verbal Learning Task (RAVLT) is a cognitive test designed to assess verbal learning and memory, including immediate memory, efficiency of learning, retroactive and proactive interference effects, and encoding versus retrieval. It consists of a number of tasks, including immediate recall and delayed recall. The number of words correctly recalled on each task is recorded.

    Measured: Baseline and Week 8

  4. Change From Baseline to Week 8 in the TMT A (Speed of Processing)

    Trail Making Test (TMT) is a cognitive test designed to assess scanning, visuomotor tracking, executive function, and cognitive flexibility. It consists of two parts, A and B: the patient must draw lines to connect consecutively numbered circles (part A) and then connect consecutively numbered and lettered circles alternating between the two sequences (part B). The time taken to complete the two parts is recorded. Part A assesses cognitive processing speed. The lower the score the faster the processing speed.

    Measured: Baseline and Week 8

  5. Change From Baseline to Week 8 in the TMT B (Executive Function)

    TMT is a cognitive test designed to assess scanning, visuomotor tracking, executive function, and cognitive flexibility. It consists of two parts, A and B: the patient must draw lines to connect consecutively numbered circles (part A) and then connect consecutively numbered and lettered circles alternating between the two sequences (part B). The time taken to complete the two parts is recorded. Part B examines executive functioning and ability to shift cognitive set. The lower the score the faster the ability to shift cognitive set.

    Measured: Baseline and Week 8

  6. Change From Baseline to Week 8 in Congruent STROOP Time to Complete (Executive Function)

    Stroop Colour Naming Test (STROOP) is a cognitive test designed to assess the ability to inhibit a prepotent response to reading words while performing a task that requires attention control. It comprises two sheets with 50 words on each, and each word is the name of a colour. On the first sheet, the Congruent STROOP Sheet, the word and ink colour match; on the Incongruent STROOP Sheet, the word and ink colour do not match. For each sheet, the patient has 4 minutes to name the ink colour of each word. When the patient finishes the sheet, or once 4 minutes is up, the clinician notes the time taken and counts the number of correct and incorrect responses. The scale ranges from 0-100, the higher score the greater the cognitive flexibility.

    Measured: Baseline and Week 8

  7. Change From Baseline to Week 8 in Incongruent STROOP Time to Complete (Executive Function)

    Measured: Baseline and Week 8

  8. Change From Baseline to Week 8 in the SRT (Speed of Processing)

    Simple Reaction Time (SRT) is designed to assess psychomotor speed, and Choice Reaction Time (CRT) is designed to assess visual attention. Two computerised tests, part of the CogState battery were used to measure SRT and CRT in milliseconds:

    • The "detection task" measures SRT: the patient presses a "yes" button, whenever an onscreen playing card is turned over.
    • The "identification task" measures CRT: the patient presses a "yes" button whenever an onscreen playing card is turned over and is red, or a "no" button if the card is not red.

    Measured: Baseline and Week 8

  9. Change From Baseline to Week 8 in the CRT (Attention)

    Measured: Baseline and Week 8

  10. Change From Baseline to Week 8 in MADRS Total Score

    The Montgomery Åsberg Depression Rating Scale (MADRS) is a depression rating scale consisting of 10 items, each rated 0 (no symptom) to 6 (severe symptom). The 10 items represent the core symptoms of depressive illness. The rating should be based on a clinical interview with the patient, moving from broadly phrased questions about symptoms to more detailed ones, which allow a precise rating of severity, covering the last 7 days. Total score from 0 to 60. The higher the score, the more severe.

    Measured: Baseline and Week 8

  11. Change From Baseline to Week 8 in CGI-S Score

    The Clinical Global Impression - Severity of Illness (CGI-S) is a 7-point scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The investigator should use his/her total clinical experience with this patient population to judge how mentally ill the patient is at the time of rating.

    Measured: Baseline and Week 8

  12. Clinical Status Using CGI-I Score at Week 8

    The Clinical Global Impression - Global Improvement (CGI-I) is a 7-point scale rated from 1 (very much improved) to 7 (very much worse). The investigator rated the patient's overall improvement relative to baseline, whether or not, in the opinion of the investigator, this was entirely due to the drug treatment.

    Measured: Week 8

  13. Proportion of Responders at Week 8 (Response Defined as a >=50% Decrease in the MADRS Total Score From Baseline

    Measured: Baseline and Week 8

  14. Proportion of Remitters at Week 8 (Remission is Defined as a MADRS Total Score <=10)

    Measured: Week 8

  15. Change From Baseline to Week 1 Using the MADRS Total Score and the Composite Z-score

    Effect on cognitive dysfunction after correcting for the effect on depressive symptoms.

    The estimation of the effect on cognitive dysfunction after correcting for the effect on depressive symptoms was based on the composite z-score and the MADRS total score. The effect was estimated in an ANCOVA model using the composite z-score at week 1 as dependent variable and the change from baseline to week 1 in the MADRS total score, the baseline MADRS total score, the baseline composite z-score, the treatment group and site as independent variables.

    In the week 1 analysis the vortioxetine 10 and 20 mg groups were pooled because patients randomized to vortioxetine 20 mg received vortioxetine 10 mg in the first week of the study.

    Measured: Baseline and Week 1

  16. Change From Baseline to Week 8 Using the MADRS Total Score and the Composite Z-score

    Effect on cognitive dysfunction after correcting for the effect on depressive symptoms.

    The estimation of the effect on cognitive dysfunction after correcting for the effect on depressive symptoms was based on the composite z-score and the MADRS total score. The effect was estimated in an ANCOVA model using the composite z-score at week 1 as dependent variable and the change from baseline to week 1 in the MADRS total score, the baseline MADRS total score, the baseline composite z-score, the treatment group and site as independent variables.

    Measured: Baseline and Week 8

  17. Risk of Suicidality Using C-SSRS Scores

    The Columbia-Suicide Severity Rating Scale (C-SSRS) was developed by researchers at Columbia University as a tool to systematically assess suicidal ideation and behaviour in patients during participation in a clinical study. The C-SSRS is composed of questions that address suicidal behaviour and questions that address suicidal ideation, with subquestions that assess severity. The tool was administered via an interview with the patient.

    For 2 patients in each treament group (6 in total) the CSSRS assessments are missing during study.

    Measured: Up to 8 weeks

Timeline

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

  1. First posted23 Aug 2011 (estimated)
  2. Study startDec 2011
  3. Primary completionMay 2013

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
598 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01422213
Sponsor's protocol ID
14122A
Other IDs
2011-001572-19
Acronym
FOCUS
Status last verified
Jul 2014
First submitted
22 Aug 2011
Last updated
5 Aug 2014
Data monitoring committee
No

Publications

  • Nohr AK, Lindow M, Forsingdal A, Demharter S, Nielsen T, Buller R, Moltke I, Vitezic M, Albrechtsen A. A large-scale genome-wide gene expression analysis in peripheral blood identifies very few differentially expressed genes related to antidepressant treatment and response in patients with major depressive disorder. Neuropsychopharmacology. 2021 Jun;46(7):1324-1332. doi: 10.1038/s41386-021-01002-9. Epub 2021 Apr 8.

    PubMed 33833401
  • McIntyre RS, Florea I, Tonnoir B, Loft H, Lam RW, Christensen MC. Efficacy of Vortioxetine on Cognitive Functioning in Working Patients With Major Depressive Disorder. J Clin Psychiatry. 2017 Jan;78(1):115-121. doi: 10.4088/JCP.16m10744.

    PubMed 27780334
  • McIntyre RS, Lophaven S, Olsen CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol. 2014 Oct;17(10):1557-67. doi: 10.1017/S1461145714000546. Epub 2014 Apr 30.

    PubMed 24787143

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Vortioxetine (Lu AA21004) in people with Major Depressive Disorder, run by H. Lundbeck A/S.

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 5 inclusion and 32 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 5 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.

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 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 5 Aug 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 From Baseline to Week 8 in DSST (Number of Correct Symbols) and RAVLT (Acquisition and Delayed Recall) Using the Composite Z-score Defined as the Weighted Sum of the Individual Patient Z-scores (time frame: Baseline and Week 8). 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 NCT01422213, 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 5 Aug 2014.

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