Vortioxetine for MDD, Cognition, and Systemic Inflammatory Biomarkers

NCT02637466 | Withdrawn Phase 4 DMC

• 1 other identifier: 20150753
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this antidepressant study is to determine the efficacy of vortioxetine on depression and cognition in 80 women with breast cancer, and to elucidate inflammatory-mediated mechanisms by which depression and its treatment influence cancer outcome. Our hypothesis is that effective vortioxetine antidepressant therapy in depressed women with breast cancer will attenuate increased intermediate endpoints of inflammation that contribute to the pathogenesis of depression, cognitive impairment, and cancer progression

Conditions

Unipolar Major Depression; Stage I, II or III Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Antidepressant efficacy

  Antidepressant efficacy will be assessed by the Hamilton Depression Rating Scale-21 (HDRS-21) total score administered at specified time points. Antidepressant response is defined as a 50% reduction in baseline HDRS-21 total score, and treatment remission is defined as an HDRS-21 total score ≤7. Antidepressants will be deemed effective if the patient's depression does not worsen. A participant's depression will be classified as "worse" if a) the participant becomes suicidal or psychotic, b) their HAM-D score increases \> 18, or over a four-week period of time: c) the HAM-D score increases, and d) the CGI Improvement Rating has increased by at least one point. The definitions of antidepressant efficacy and worsening depression remain the same during Cycle 2.

  4-16 weeks

Study Arms (2)

Vortioxetine

EXPERIMENTAL

In cycle I of the study, participants will be randomized on to flexible-dose VTX (10-20 mg) versus. Vortioxetine starting dose will be 10 mg daily. Vortioxetine starting dose will be 10 mg daily with a dose escalation up to 20 mg daily at week #4. Study cycle II is an 8-week, open label treatment design for non-responders completing the Cycle I RCT. One treatment arm will continue VTX non-responders to 8 week VTX (10-20 mg/day) augmentation with cognitive behavioral therapy (10 sessions). The 2nd treatment arm will continue placebo non-responders who complete the RCT to VTX (10 to 20 mg/day). The third treatment arm will continue VTX responders/remitters who complete the RCT to open-label VTX for another 8-weeks to assess maintenance efficacy for up to 16 weeks.

Drug: Vortioxetine

Placebo

PLACEBO COMPARATOR

In cycle I of the study, 80 eligible depressed women with breast cancer will be randomized into an 8-week, double-blind, placebo-controlled, flexible-dose vortioxetine (10-20 mg) treatment arm versus placebo arm. Responders to placebo treatment will complete their study participation at the end of Cycle I, and will not proceed to Cycle II.

Drug: Vortioxetine

Interventions

Vortioxetine DRUG

Also known as: Brilliantex

Placebo; Vortioxetine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients 18 to 75 years of age
• Confirmed diagnosis of Stage I, II, or III breast cancer
• Completed curative cancer treatment (surgery, chemotherapy, and/or radiotherapy) at least four weeks (≥ 4 weeks) prior to study entry no more than 5 years.
• Unipolar major depression confirmed by the mood disorder module in Structured Clinical interview for DSM-V (SCID)
• Baseline depression severity total score ≥18 by Hamilton Depression Rating Scale-21 (HDRS-21)
• Negative urine pregnancy test in women of child-bearing potential (WOCBP).
• Use of medically-established contraceptive method (e.g., contraceptive hormone therapy or intrauterine device) in women of child-bearing potential (WOCBP) or abstinence from heterosexual intercourse from the time of signing informed consent through 14 days after the last dose of study drug.
• Ability to understand and the willingness to sign a written informed consent and HIPAA document/s

You may not qualify if:

• \. Other active cancers \[EXCEPTION: cured skin cancer\]. 2. Actively suicidal, as determined by certified mental health provider. 3. Comorbid bipolar disorder or psychosis, as diagnosed by psychiatric clinical interview conducted by a certified mental health provider.
• \. Mini-mental state exam (MMSE) score \<24 at baseline assessment 5. Current use of stimulant and/or amphetamine for cancer-related fatigue or cognitive impairment.
• \. Use of current and effective antidepressants during study period. \[NOTE: Patients who have not responded to current antidepressant may be tapered off medication prior to study entry.\] 7. Uncontrolled hypothyroidism. Must be biochemically (TSH, T3, T4) and clinically euthyroid at baseline assessment.
• \. Use of monoamine oxidase inhibitors (MAOIs) in past 14 days. 9. Concomitant use of mood stabilizer including lithium, lamictal and atypical antipsychotics 10. Failed prior therapy with vortioxetine (VTX) 11. Positive urine toxicology screen for cocaine, opiates, marijuana, amphetamines.
• \. Comorbid alcohol and/or substance use disorder within the prior 12 months of screening, as diagnosed by psychiatric clinical interview conducted by a certified mental health provider.

Sponsors & Collaborators

• University of Miami: lead
• Takeda: collaborator

MeSH Terms

Interventions

Vortioxetine

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Dominique Musselman, M.D., MSCR

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 17, 2015
• First Posted: December 22, 2015
• Study Start: July 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2019
• Last Updated: September 30, 2016

Record last verified: 2016-09