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

NCT01422213 | Completed Phase 3 Results

• 2 other identifiers: 14122A2011-001572-19
• Study Type: interventional
• Target: 598
• Locations: 0 countries
• Sites: N/A

Brief 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). 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.

Conditions

Major Depressive Disorder

Keywords

MDD; Cognitive dysfunction

Outcome Measures

Primary Outcomes (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.

  Baseline and Week 8

Secondary Outcomes (17)

• Change From Baseline to Week 8 in DSST (Number of Correct Symbols)

  Baseline and Week 8

• Change From Baseline to Week 8 in RAVLT (Acquisition)

  Baseline and Week 8

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

  Baseline and Week 8

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

  Baseline and Week 8

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

  Baseline and Week 8

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Vortioxetine 10 mg

EXPERIMENTAL

Drug: Vortioxetine (Lu AA21004)

Vortioxetine 20 mg

EXPERIMENTAL

Drug: Vortioxetine (Lu AA21004)

Interventions

Placebo DRUG

capsules; daily; orally

Placebo

Vortioxetine (Lu AA21004) DRUG

encapsulated tablets; daily; orally

Also known as: Brintellix

Vortioxetine 10 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• H. Lundbeck A/S: lead

Related Publications (3)

• 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.

  PMID: 33833401 DERIVED

• 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.

  PMID: 27780334 DERIVED

• 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.

  PMID: 24787143 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Cognitive Dysfunction

Interventions

Vortioxetine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: H. Lundbeck A/S
• Organization: H. Lundbeck A/S

LundbeckClinicalTrials@lundbeck.com

+45 3630 1311

Study Officials

• Email contact via H. Lundbeck A/S

  LundbeckClinicalTrials@lundbeck.com

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2011
• First Posted: August 23, 2011
• Study Start: December 1, 2011
• Primary Completion: May 1, 2013
• Last Updated: August 5, 2014
• Results First Posted: August 5, 2014

Record last verified: 2014-07