International Study to Predict Optimised Treatment - in Depression

NCT ID: NCT00693849

Last Updated: 2018-07-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

2688 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-09-30

Study Completion Date

2019-12-31

Brief Summary

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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

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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.

Conditions

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Major Depressive Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

NONE

Study Groups

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A

Escitalopram

Group Type ACTIVE_COMPARATOR

Escitalopram

Intervention Type DRUG

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

B

Sertraline

Group Type ACTIVE_COMPARATOR

Sertraline

Intervention Type DRUG

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

C

Venlafaxine-XR

Group Type ACTIVE_COMPARATOR

Venlafaxine-XR

Intervention Type DRUG

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

D

Healthy matched controls

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Escitalopram

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

Intervention Type DRUG

Sertraline

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

Intervention Type DRUG

Venlafaxine-XR

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

Intervention Type DRUG

Other Intervention Names

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Lexapro Zoloft Effexor

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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BRC Operations Pty. Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anthony Harris, MD

Role: PRINCIPAL_INVESTIGATOR

Brain Dynamics Centre

Barbara A. Cohen, PhD

Role: PRINCIPAL_INVESTIGATOR

Center for Healing the Human Spirit

Bruce Russell, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Auckland, New Zealand

Charles Debattista, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Con Stough, PhD

Role: PRINCIPAL_INVESTIGATOR

Swinburne University

Elizabeth Wallis, PhD

Role: PRINCIPAL_INVESTIGATOR

Brain Health Lab

Harbans Multani, MD

Role: PRINCIPAL_INVESTIGATOR

Shanti Clinical Trials

Jayashri Kulkarni, Prof

Role: PRINCIPAL_INVESTIGATOR

The Alfred and Delmont Private Hospital

Jeffrey Wilson, PhD

Role: PRINCIPAL_INVESTIGATOR

A.D.D. Treatment Center

Kamran Fallahpour, PhD

Role: PRINCIPAL_INVESTIGATOR

Brain Resource Center

Larry Hirshberg, PhD

Role: PRINCIPAL_INVESTIGATOR

NeuroDevelopment Center

Martijn Arns, PhD

Role: PRINCIPAL_INVESTIGATOR

Brainclinics Diagnostics B.V.

Mona Ismail, MD

Role: PRINCIPAL_INVESTIGATOR

Brain Resource Center

Paul Fitzgerald, PhD

Role: PRINCIPAL_INVESTIGATOR

The Alfred

Richard Clark, PhD

Role: PRINCIPAL_INVESTIGATOR

Flinders University

Roger deBeus, PhD

Role: PRINCIPAL_INVESTIGATOR

Skyland Behavioral Health Associates

Steven Bruce, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Missouri, St. Louis

Subhdeep Virk, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Tim Usherwood, MD

Role: PRINCIPAL_INVESTIGATOR

Brain Dynamics Centre

XiaoLei Yu Baran, MD

Role: PRINCIPAL_INVESTIGATOR

Cornell University

Radu V Saveanu, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

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Shanti Clinical Trials

Colton, California, United States

Site Status

A.D.D. Treatment Center

Mission Viejo, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

Veteran Affairs/Stanford University

Stanford, California, United States

Site Status

Center for Healing the Human Spirit

Tarzana, California, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

University of Missouri - St. Louis

St Louis, Missouri, United States

Site Status

Brain Resource Center

Englewood Cliffs, New Jersey, United States

Site Status

Brain Resource Center

New York, New York, United States

Site Status

Weill Cornell Medical College

White Plains, New York, United States

Site Status

Skyland Behavioral Health Associates , P.A.

Asheville, North Carolina, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

NeuroDevelopment Center

Providence, Rhode Island, United States

Site Status

Brain Dynamics Centre

Westmead, New South Wales, Australia

Site Status

Flinders University

Adelaide, South Australia, Australia

Site Status

Swinburne University

Melbourne, Victoria, Australia

Site Status

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Brainclinics Diagnostics B.V.

Nijmegen, Gelderland, Netherlands

Site Status

University of Auckland

Auckland, , New Zealand

Site Status

Brain Health Lab

Johannesburg, Guatang, South Africa

Site Status

Countries

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United States Australia Netherlands New Zealand South Africa

References

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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.

Reference Type DERIVED
PMID: 37318808 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37201900 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34349116 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33647333 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33230268 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32568399 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31695168 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31601424 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31513968 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31477195 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31341158 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31023398 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30710613 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30311742 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29133948 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28237506 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27791054 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27137427 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26995298 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26282359 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26137532 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25917683 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25824424 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25815420 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25815419 (View on PubMed)

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.

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PMID: 24970773 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24690111 (View on PubMed)

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.

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PMID: 24679400 (View on PubMed)

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.

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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.

Reference Type DERIVED
PMID: 22562047 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21208417 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21170955 (View on PubMed)

Related Links

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http://www.ANZCTR.org.au/ACTRN12608000476336.aspx

Australian New Zealand Clinical Trials Registry

Other Identifiers

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iSPOT-D

Identifier Type: -

Identifier Source: org_study_id

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