Clinical trial NCT00693849: International Study to Predict Optimised Treatment - in Depression
Official title: International Study to Predict Optimised Treatment - in Depression
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Major Depressive Disorder
Keywords: depression
CNS
iSPOT
MDD
Lead sponsor: BRC Operations Pty. Ltd.
Sponsor class: INDUSTRY
First posted: 2008-06-09
Enrollment: 2688
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The aim of this study is to identify genetic, physical (brain) and psychological (cognitive) markers (or combinations of them) that predict specific response to a range of antidepressants treatment (Escitalopram, Venlafaxine, Sertraline) in patients diagnosed with major depressive disorder. This study is focused on outcomes which may impact on how "personalised medicine" is implemented in depression.

Detailed description: This is an open-label, randomised (effectiveness) study (ie. comparison of active treatments) to identify genetic markers, brain function, brain structure, and psychological and cognitive indicators (or a combination of markers) in MDD subjects versus healthy controls. Approximately 2,016 subjects with major depressive disorder (MDD) across multiple international sites (USA, Canada, UK, South Africa, New Zealand, The Netherlands and Australia) will be randomised to one of three approved and effective treatment arms:

Treatment A Escitalopram. Treatment B Sertraline. Treatment C Venlafaxine XR.

A group of matched healthy controls (n = 672) will also be enrolled.

Subjects will be asked to attend the testing facility on two separate occasions; for Pre-treatment (Pre-Tx) and at 8 weeks post initiation of treatment. The assessments/procedures at Pre-Tx and Week 8 include: Baseline a clinical work-up, blood collection for genetic analyses, cognitive testing and electrical brain functioning (EEG/ERP). Structural and functional data MRI data will be collected in ten percent (10%) of participants.

On Day 4 and Weeks 2, 4, 6, 12, 16, 24 and 52 Subjects will be contacted by phone and asked to complete 2 questionnaires via the internet.

Eligibility criteria: Inclusion Criteria:

* Meet DSM-IV criteria for primary diagnosis of MDD.
* HAM-D17 score of ≥ 16.
* 18-65 years age-range
* Subjects with English or Dutch literacy and fluency.
* Written, informed consent.

Exclusion Criteria:

* Presence of suicidal ideations and/or tendencies (as determined by a score \>12 on Section C, Suicidality, of the MINI Plus), Bipolar I-III, psychosis, primary eating disorders, Post Traumatic Stress Disorder (PTSD), Obsessive Compulsive Disorder (OCD), Post-Natal Depression as well as any Axis II personality disorders as diagnosed using the MINI Plus or by a health care professional.
* Pregnancy and women of child bearing potential who are not taking a medically accepted form of contraception and are at risk of becoming pregnant during the study.
* Breastfeeding.
* Known contra-indication or intolerance to the use of Escitalopram, Sertraline or Venlafaxine XR as defined in the product package insert for each drug (including previous treatment failure at the highest recommended dose).
* Use of any psychological or counselling therapy or antidepressant/CNS drug which cannot be washed out prior to participation and eliminated until after Week 8 or discontinuation.
* Use of any medication which is known to be contraindicated with Escitalopram, Sertraline, or Venlafaxine XR (refer to the product package insert for each drug).
* Known medical condition, disease or neurological disorder which might, in the opinion of investigator/s, interfere with the assessments to be made in the study or put subjects at increased risk when exposed to optimal doses of the drug treatment.
* History of head injury with loss of consciousness for at least 10 minutes.
* Recent/current substance dependence (as defined in Section K of the Mini Plus as per a 6 months period and/or alcoholism) in the past six months.
* Participation in an investigational study within four months of the baseline visit in which subjects have received an experimental drug/device that could affect the primary end points of this study.
* Subjects who, in the opinion of the investigator, have a severe impediment to vision, hearing and/or hand movement, which is likely to interfere with their ability to complete the test batteries.
* Subjects who, in the opinion of the investigator, are unable and/or unlikely to comprehend and follow the study procedures and instructions.

Primary outcomes:
measure: To determine whether the genetic-brain-cognition function markers (or combination of markers) 'normalise' with acute drug treatment in MDD
timeFrame: Week 8
Secondary outcomes:
measure: To determine whether markers of acute treatment prediction are also predictive of functional outcome over 6-12 months.
timeFrame: 52-weeks
Other outcomes:
Locations:
city: Colton
country: United States
facility: Shanti Clinical Trials
state: California
city: Mission Viejo
country: United States
facility: A.D.D. Treatment Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Stanford
country: United States
facility: Veteran Affairs/Stanford University
state: California
city: Tarzana
country: United States
facility: Center for Healing the Human Spirit
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Saint Louis
country: United States
facility: University of Missouri - St. Louis
state: Missouri
city: Englewood Cliffs
country: United States
facility: Brain Resource Center
state: New Jersey
city: New York
country: United States
facility: Brain Resource Center
state: New York
city: White Plains
country: United States
facility: Weill Cornell Medical College
state: New York
city: Asheville
country: United States
facility: Skyland Behavioral Health Associates , P.A.
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Providence
country: United States
facility: NeuroDevelopment Center
state: Rhode Island
city: Westmead
country: Australia
facility: Brain Dynamics Centre
state: New South Wales
city: Adelaide
country: Australia
facility: Flinders University
state: South Australia
city: Melbourne
country: Australia
facility: Swinburne University
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Nijmegen
country: Netherlands
facility: Brainclinics Diagnostics B.V.
state: Gelderland
city: Auckland
country: New Zealand
facility: University of Auckland
city: Johannesburg
country: South Africa
facility: Brain Health Lab
state: Guatang
Study officials:
affiliation: Brain Dynamics Centre
name: Anthony Harris, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Center for Healing the Human Spirit
name: Barbara A. Cohen, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Auckland, New Zealand
name: Bruce Russell, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Charles Debattista, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Swinburne University
name: Con Stough, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brain Health Lab
name: Elizabeth Wallis, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanti Clinical Trials
name: Harbans Multani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Alfred and Delmont Private Hospital
name: Jayashri Kulkarni, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: A.D.D. Treatment Center
name: Jeffrey Wilson, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brain Resource Center
name: Kamran Fallahpour, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: NeuroDevelopment Center
name: Larry Hirshberg, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brainclinics Diagnostics B.V.
name: Martijn Arns, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brain Resource Center
name: Mona Ismail, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Alfred
name: Paul Fitzgerald, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Flinders University
name: Richard Clark, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Skyland Behavioral Health Associates
name: Roger deBeus, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Missouri, St. Louis
name: Steven Bruce, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ohio State University
name: Subhdeep Virk, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brain Dynamics Centre
name: Tim Usherwood, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cornell University
name: XiaoLei Yu Baran, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Miami
name: Radu V Saveanu, MD
role: PRINCIPAL_INVESTIGATOR
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