International Study to Predict Optimised Treatment - in Depression

NCT00693849 | Unknown Phase 4

• 1 other identifier: iSPOT-D
• Study Type: interventional
• Target: 2,688
• Locations: 5 countries
• Sites: 20

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.

Conditions

Major Depressive Disorder

Keywords

depression; CNS; iSPOT; MDD

Outcome Measures

Primary Outcomes (1)

• To determine whether the genetic-brain-cognition function markers (or combination of markers) 'normalise' with acute drug treatment in MDD

  Week 8

Secondary Outcomes (1)

• To determine whether markers of acute treatment prediction are also predictive of functional outcome over 6-12 months.

  52-weeks

Study Arms (4)

A

ACTIVE COMPARATOR

Escitalopram

Drug: Escitalopram

B

ACTIVE COMPARATOR

Sertraline

Drug: Sertraline

C

ACTIVE COMPARATOR

Venlafaxine-XR

Drug: Venlafaxine-XR

D

NO INTERVENTION

Healthy matched controls

Interventions

Escitalopram DRUG

10 mg/day as a single dose, increased to max 20 mg/day

Also known as: Lexapro

A

Sertraline DRUG

50 mg/day as a single dose, increased to max of 200 mg/day

Also known as: Zoloft

B

Venlafaxine-XR DRUG

75 mg/day given once daily; increased to 150-225 mg/day

Also known as: Effexor

C

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• BRC Operations Pty. Ltd.: lead

Study Sites (20)

Shanti Clinical Trials

Colton, California, 92324, United States

Location

A.D.D. Treatment Center

Mission Viejo, California, 92691, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Veteran Affairs/Stanford University

Stanford, California, 94305, United States

Location

Center for Healing the Human Spirit

Tarzana, California, 91356, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of Missouri - St. Louis

St Louis, Missouri, 63121, United States

Location

Brain Resource Center

Englewood Cliffs, New Jersey, 07632, United States

Location

Brain Resource Center

New York, New York, 10023, United States

Location

Weill Cornell Medical College

White Plains, New York, 10605, United States

Location

Skyland Behavioral Health Associates , P.A.

Asheville, North Carolina, 28801, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

NeuroDevelopment Center

Providence, Rhode Island, 02903, United States

Location

Brain Dynamics Centre

Westmead, New South Wales, 2145, Australia

Location

Flinders University

Adelaide, South Australia, 5042, Australia

Location

Swinburne University

Melbourne, Victoria, 3122, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3181, Australia

Location

Brainclinics Diagnostics B.V.

Nijmegen, Gelderland, 6524 AD, Netherlands

Location

University of Auckland

Auckland, 1142, New Zealand

Location

Brain Health Lab

Johannesburg, Guatang, 2191, South Africa

Location

Related Publications (32)

• Hack LM, Tozzi L, Zenteno S, Olmsted AM, Hilton R, Jubeir J, Korgaonkar MS, Schatzberg AF, Yesavage JA, O'Hara R, Williams LM. A Cognitive Biotype of Depression and Symptoms, Behavior Measures, Neural Circuits, and Differential Treatment Outcomes: A Prespecified Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2023 Jun 1;6(6):e2318411. doi: 10.1001/jamanetworkopen.2023.18411.

  PMID: 37318808 DERIVED

• Hietamies TM, McInnes LA, Klise AJ, Worley MJ, Qian JJ, Williams LM, Heifets BD, Levine SP. The effects of ketamine on symptoms of depression and anxiety in real-world care settings: A retrospective controlled analysis. J Affect Disord. 2023 Aug 15;335:484-492. doi: 10.1016/j.jad.2023.04.141. Epub 2023 May 16.

  PMID: 37201900 DERIVED

• Braund TA, Tillman G, Palmer DM, Gordon E, Rush AJ, Harris AWF. Antidepressant side effects and their impact on treatment outcome in people with major depressive disorder: an iSPOT-D report. Transl Psychiatry. 2021 Aug 4;11(1):417. doi: 10.1038/s41398-021-01533-1.

  PMID: 34349116 DERIVED

• Krepel N, Benschop L, Baeken C, Sack AT, Arns M. An EEG signature of suicidal behavior in female patients with major depressive disorder? A non-replication. Biol Psychol. 2021 Apr;161:108058. doi: 10.1016/j.biopsycho.2021.108058. Epub 2021 Feb 26.

  PMID: 33647333 DERIVED

• Fischer AS, Holt-Gosselin B, Fleming SL, Hack LM, Ball TM, Schatzberg AF, Williams LM. Intrinsic reward circuit connectivity profiles underlying symptom and quality of life outcomes following antidepressant medication: a report from the iSPOT-D trial. Neuropsychopharmacology. 2021 Mar;46(4):809-819. doi: 10.1038/s41386-020-00905-3. Epub 2020 Nov 23.

  PMID: 33230268 DERIVED

• Rajpurkar P, Yang J, Dass N, Vale V, Keller AS, Irvin J, Taylor Z, Basu S, Ng A, Williams LM. Evaluation of a Machine Learning Model Based on Pretreatment Symptoms and Electroencephalographic Features to Predict Outcomes of Antidepressant Treatment in Adults With Depression: A Prespecified Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e206653. doi: 10.1001/jamanetworkopen.2020.6653.

  PMID: 32568399 DERIVED

• Korgaonkar MS, Goldstein-Piekarski AN, Fornito A, Williams LM. Intrinsic connectomes are a predictive biomarker of remission in major depressive disorder. Mol Psychiatry. 2020 Jul;25(7):1537-1549. doi: 10.1038/s41380-019-0574-2. Epub 2019 Nov 6.

  PMID: 31695168 DERIVED

• Tozzi L, Goldstein-Piekarski AN, Korgaonkar MS, Williams LM. Connectivity of the Cognitive Control Network During Response Inhibition as a Predictive and Response Biomarker in Major Depression: Evidence From a Randomized Clinical Trial. Biol Psychiatry. 2020 Mar 1;87(5):462-472. doi: 10.1016/j.biopsych.2019.08.005. Epub 2019 Aug 21.

  PMID: 31601424 DERIVED

• Braund TA, Tillman G, Palmer DM, Harris AWF. Verbal memory predicts treatment outcome in syndromal anxious depression: An iSPOT-D report. J Affect Disord. 2020 Jan 1;260:245-253. doi: 10.1016/j.jad.2019.09.028. Epub 2019 Sep 4.

  PMID: 31513968 DERIVED

• Keller AS, Ball TM, Williams LM. Deep phenotyping of attention impairments and the 'Inattention Biotype' in Major Depressive Disorder. Psychol Med. 2020 Oct;50(13):2203-2212. doi: 10.1017/S0033291719002290. Epub 2019 Sep 3.

  PMID: 31477195 DERIVED

• Hellewell SC, Welton T, Maller JJ, Lyon M, Korgaonkar MS, Koslow SH, Williams LM, Rush AJ, Gordon E, Grieve SM. Profound and reproducible patterns of reduced regional gray matter characterize major depressive disorder. Transl Psychiatry. 2019 Jul 24;9(1):176. doi: 10.1038/s41398-019-0512-8.

  PMID: 31341158 DERIVED

• Braund TA, Palmer DM, Williams LM, Harris AWF. Dimensions of anxiety in Major depressive disorder and their use in predicting antidepressant treatment outcome: an iSPOT-D report. Psychol Med. 2020 Apr;50(6):1032-1042. doi: 10.1017/S0033291719000941. Epub 2019 Apr 26.

  PMID: 31023398 DERIVED

• Graziano RC, Bruce SE, Paul RH, Korgaonkar MS, Williams LM. The effects of bullying in depression on white matter integrity. Behav Brain Res. 2019 May 2;363:149-154. doi: 10.1016/j.bbr.2019.01.054. Epub 2019 Jan 30.

  PMID: 30710613 DERIVED

• Kircanski K, Williams LM, Gotlib IH. Heart rate variability as a biomarker of anxious depression response to antidepressant medication. Depress Anxiety. 2019 Jan;36(1):63-71. doi: 10.1002/da.22843. Epub 2018 Oct 12.

  PMID: 30311742 DERIVED

• Maller JJ, Broadhouse K, Rush AJ, Gordon E, Koslow S, Grieve SM. Increased hippocampal tail volume predicts depression status and remission to anti-depressant medications in major depression. Mol Psychiatry. 2018 Aug;23(8):1737-1744. doi: 10.1038/mp.2017.224. Epub 2017 Nov 14.

  PMID: 29133948 DERIVED

• Iseger TA, Korgaonkar MS, Kenemans JL, Grieve SM, Baeken C, Fitzgerald PB, Arns M. EEG connectivity between the subgenual anterior cingulate and prefrontal cortices in response to antidepressant medication. Eur Neuropsychopharmacol. 2017 Apr;27(4):301-312. doi: 10.1016/j.euroneuro.2017.02.002. Epub 2017 Feb 23.

  PMID: 28237506 DERIVED

• Goldstein-Piekarski AN, Korgaonkar MS, Green E, Suppes T, Schatzberg AF, Hastie T, Nemeroff CB, Williams LM. Human amygdala engagement moderated by early life stress exposure is a biobehavioral target for predicting recovery on antidepressants. Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):11955-11960. doi: 10.1073/pnas.1606671113. Epub 2016 Oct 10.

  PMID: 27791054 DERIVED

• Grieve SM, Korgaonkar MS, Gordon E, Williams LM, Rush AJ. Prediction of nonremission to antidepressant therapy using diffusion tensor imaging. J Clin Psychiatry. 2016 Apr;77(4):e436-43. doi: 10.4088/JCP.14m09577.

  PMID: 27137427 DERIVED

• Shilyansky C, Williams LM, Gyurak A, Harris A, Usherwood T, Etkin A. Effect of antidepressant treatment on cognitive impairments associated with depression: a randomised longitudinal study. Lancet Psychiatry. 2016 May;3(5):425-35. doi: 10.1016/S2215-0366(16)00012-2. Epub 2016 Mar 16.

  PMID: 26995298 DERIVED

• van Dinteren R, Arns M, Kenemans L, Jongsma ML, Kessels RP, Fitzgerald P, Fallahpour K, Debattista C, Gordon E, Williams LM. Utility of event-related potentials in predicting antidepressant treatment response: An iSPOT-D report. Eur Neuropsychopharmacol. 2015 Nov;25(11):1981-90. doi: 10.1016/j.euroneuro.2015.07.022. Epub 2015 Aug 6.

  PMID: 26282359 DERIVED

• Korgaonkar MS, Rekshan W, Gordon E, Rush AJ, Williams LM, Blasey C, Grieve SM. Magnetic Resonance Imaging Measures of Brain Structure to Predict Antidepressant Treatment Outcome in Major Depressive Disorder. EBioMedicine. 2014 Dec 3;2(1):37-45. doi: 10.1016/j.ebiom.2014.12.002. eCollection 2015 Jan.

  PMID: 26137532 DERIVED

• Miller S, McTeague LM, Gyurak A, Patenaude B, Williams LM, Grieve SM, Korgaonkar MS, Etkin A. COGNITION-CHILDHOOD MALTREATMENT INTERACTIONS IN THE PREDICTION OF ANTIDEPRESSANT OUTCOMES IN MAJOR DEPRESSIVE DISORDER PATIENTS: RESULTS FROM THE iSPOT-D TRIAL. Depress Anxiety. 2015 Aug;32(8):594-604. doi: 10.1002/da.22368. Epub 2015 Apr 27.

  PMID: 25917683 DERIVED

• Williams LM, Korgaonkar MS, Song YC, Paton R, Eagles S, Goldstein-Piekarski A, Grieve SM, Harris AW, Usherwood T, Etkin A. Amygdala Reactivity to Emotional Faces in the Prediction of General and Medication-Specific Responses to Antidepressant Treatment in the Randomized iSPOT-D Trial. Neuropsychopharmacology. 2015 Sep;40(10):2398-408. doi: 10.1038/npp.2015.89. Epub 2015 Mar 31.

  PMID: 25824424 DERIVED

• Schatzberg AF, DeBattista C, Lazzeroni LC, Etkin A, Murphy GM Jr, Williams LM. ABCB1 Genetic Effects on Antidepressant Outcomes: A Report From the iSPOT-D Trial. Am J Psychiatry. 2015 Aug 1;172(8):751-9. doi: 10.1176/appi.ajp.2015.14050680. Epub 2015 Mar 27.

  PMID: 25815420 DERIVED

• Arnow BA, Blasey C, Williams LM, Palmer DM, Rekshan W, Schatzberg AF, Etkin A, Kulkarni J, Luther JF, Rush AJ. Depression Subtypes in Predicting Antidepressant Response: A Report From the iSPOT-D Trial. Am J Psychiatry. 2015 Aug 1;172(8):743-50. doi: 10.1176/appi.ajp.2015.14020181. Epub 2015 Mar 27.

  PMID: 25815419 DERIVED

• Korgaonkar MS, Williams LM, Song YJ, Usherwood T, Grieve SM. Diffusion tensor imaging predictors of treatment outcomes in major depressive disorder. Br J Psychiatry. 2014 Oct;205(4):321-8. doi: 10.1192/bjp.bp.113.140376. Epub 2014 Jun 26.

  PMID: 24970773 DERIVED

• Korgaonkar MS, Fornito A, Williams LM, Grieve SM. Abnormal structural networks characterize major depressive disorder: a connectome analysis. Biol Psychiatry. 2014 Oct 1;76(7):567-74. doi: 10.1016/j.biopsych.2014.02.018. Epub 2014 Mar 6.

  PMID: 24690111 DERIVED

• McRae K, Rekshan W, Williams LM, Cooper N, Gross JJ. Effects of antidepressant medication on emotion regulation in depressed patients: an iSPOT-D report. J Affect Disord. 2014 Apr;159:127-32. doi: 10.1016/j.jad.2013.12.037. Epub 2014 Jan 5.

  PMID: 24679400 DERIVED

• Grieve SM, Korgaonkar MS, Etkin A, Harris A, Koslow SH, Wisniewski S, Schatzberg AF, Nemeroff CB, Gordon E, Williams LM. Brain imaging predictors and the international study to predict optimized treatment for depression: study protocol for a randomized controlled trial. Trials. 2013 Jul 18;14:224. doi: 10.1186/1745-6215-14-224.

  PMID: 23866851 DERIVED

• Korgaonkar MS, Cooper NJ, Williams LM, Grieve SM. Mapping inter-regional connectivity of the entire cortex to characterize major depressive disorder: a whole-brain diffusion tensor imaging tractography study. Neuroreport. 2012 Jun 20;23(9):566-71. doi: 10.1097/WNR.0b013e3283546264.

  PMID: 22562047 DERIVED

• Williams LM, Rush AJ, Koslow SH, Wisniewski SR, Cooper NJ, Nemeroff CB, Schatzberg AF, Gordon E. International Study to Predict Optimized Treatment for Depression (iSPOT-D), a randomized clinical trial: rationale and protocol. Trials. 2011 Jan 5;12:4. doi: 10.1186/1745-6215-12-4.

  PMID: 21208417 DERIVED

• Korgaonkar MS, Grieve SM, Koslow SH, Gabrieli JD, Gordon E, Williams LM. Loss of white matter integrity in major depressive disorder: evidence using tract-based spatial statistical analysis of diffusion tensor imaging. Hum Brain Mapp. 2011 Dec;32(12):2161-71. doi: 10.1002/hbm.21178. Epub 2010 Dec 17.

  PMID: 21170955 DERIVED

Related Links

• Australian New Zealand Clinical Trials Registry

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Escitalopram; Sertraline; Venlafaxine Hydrochloride

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; 1-Naphthylamine; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Phenethylamines; Ethylamines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Lipids

Study Officials

• Anthony Harris, MD

  Brain Dynamics Centre

  PRINCIPAL INVESTIGATOR

• Barbara A. Cohen, PhD

  Center for Healing the Human Spirit

  PRINCIPAL INVESTIGATOR

• Bruce Russell, PhD

  University of Auckland, New Zealand

  PRINCIPAL INVESTIGATOR

• Charles Debattista, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Con Stough, PhD

  Swinburne University

  PRINCIPAL INVESTIGATOR

• Elizabeth Wallis, PhD

  Brain Health Lab

  PRINCIPAL INVESTIGATOR

• Harbans Multani, MD

  Shanti Clinical Trials

  PRINCIPAL INVESTIGATOR

• Jayashri Kulkarni, Prof

  The Alfred and Delmont Private Hospital

  PRINCIPAL INVESTIGATOR

• Jeffrey Wilson, PhD

  A.D.D. Treatment Center

  PRINCIPAL INVESTIGATOR

• Kamran Fallahpour, PhD

  Brain Resource Center

  PRINCIPAL INVESTIGATOR

• Larry Hirshberg, PhD

  NeuroDevelopment Center

  PRINCIPAL INVESTIGATOR

• Martijn Arns, PhD

  Brainclinics Diagnostics B.V.

  PRINCIPAL INVESTIGATOR

• Mona Ismail, MD

  Brain Resource Center

  PRINCIPAL INVESTIGATOR

• Paul Fitzgerald, PhD

  The Alfred

  PRINCIPAL INVESTIGATOR

• Richard Clark, PhD

  Flinders University

  PRINCIPAL INVESTIGATOR

• Roger deBeus, PhD

  Skyland Behavioral Health Associates

  PRINCIPAL INVESTIGATOR

• Steven Bruce, PhD

  University of Missouri, St. Louis

  PRINCIPAL INVESTIGATOR

• Subhdeep Virk, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

• Tim Usherwood, MD

  Brain Dynamics Centre

  PRINCIPAL INVESTIGATOR

• XiaoLei Yu Baran, MD

  Cornell University

  PRINCIPAL INVESTIGATOR

• Radu V Saveanu, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2008
• First Posted: June 9, 2008
• Study Start: September 1, 2008
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: July 11, 2018

Record last verified: 2018-07

Locations

US (13); NZ (1); AU (4); ZA (1); NL (1)