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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00693849




Registration number
NCT00693849
Ethics application status
Date submitted
6/06/2008
Date registered
9/06/2008
Date last updated
11/07/2018

Titles & IDs
Public title
International Study to Predict Optimised Treatment - in Depression
Scientific title
International Study to Predict Optimised Treatment - in Depression
Secondary ID [1] 0 0
iSPOT-D
Universal Trial Number (UTN)
Trial acronym
iSPOT-D
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Major Depressive Disorder 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Escitalopram
Treatment: Drugs - Sertraline
Treatment: Drugs - Venlafaxine-XR

Active comparator: A - Escitalopram

Active comparator: B - Sertraline

Active comparator: C - Venlafaxine-XR

No intervention: D - Healthy matched controls


Treatment: Drugs: Escitalopram
10 mg/day as a single dose, increased to max 20 mg/day

Treatment: Drugs: Sertraline
50 mg/day as a single dose, increased to max of 200 mg/day

Treatment: Drugs: Venlafaxine-XR
75 mg/day given once daily; increased to 150-225 mg/day

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To determine whether the genetic-brain-cognition function markers (or combination of markers) 'normalise' with acute drug treatment in MDD
Timepoint [1] 0 0
Week 8
Secondary outcome [1] 0 0
To determine whether markers of acute treatment prediction are also predictive of functional outcome over 6-12 months.
Timepoint [1] 0 0
52-weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Brain Dynamics Centre - Westmead
Recruitment hospital [2] 0 0
Flinders University - Adelaide
Recruitment hospital [3] 0 0
Swinburne University - Melbourne
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
5042 - Adelaide
Recruitment postcode(s) [3] 0 0
3122 - Melbourne
Recruitment postcode(s) [4] 0 0
3181 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Rhode Island
Country [9] 0 0
Netherlands
State/province [9] 0 0
Gelderland
Country [10] 0 0
New Zealand
State/province [10] 0 0
Auckland
Country [11] 0 0
South Africa
State/province [11] 0 0
Guatang

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
BRC Operations Pty. Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00693849
Trial related presentations / publications
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.
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.
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.
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. Erratum In: JAMA Netw Open. 2020 Jul 1;3(7):e2016001. doi: 10.1001/jamanetworkopen.2020.16001.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Anthony Harris, MD
Address 0 0
Brain Dynamics Centre
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00693849