The Effects of ECT and/or iTBS on Olfaction and Cognition in Patients With Depression

NCT ID: NCT02804347

Last Updated: 2017-09-06

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

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

30 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-03-31

Study Completion Date

2017-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The sense of smell and cognition are known to be closely associated with mood and emotional processes. However, despite the clear links between olfaction and cognitive processes with emotional states, research into the role of olfaction, cognition, and mood disorders has so far yielded variable results. This study proposes to investigate the ability to detect and identify odours and assess cognition in a group of patients with unipolar and bipolar depression prior to and after receiving their scheduled electroconvulsive therapy (ECT) or intermittent theta burst stimulation (iTBS) treatments. Olfaction will be evaluated utilizing standard olfactory testing protocols using commercially available kits. Cognition will be evaluated utilizing standard cognitive test protocols in a functional magnetic resonance imaging protocol. The results will potentially shed light on the link between olfaction, cognition and mood disorders.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The research to date indicates that olfactory sensitivity and cognition are reduced in depressed patients. The data also suggest that higher order cognitive odour evaluation, measured via identification testing, is not altered in depression. Furthermore, research into the effect (if any) of treatment on olfactory performance (sensitivity and identification) has been sparse. Researchers have called for studies that examine olfactory sensitivity prior to psychiatric treatment and post-remission. To the best of our knowledge there has yet to be a study on the effect of electroconvulsive therapy (ECT) or intermittent theta burst stimulation (iTBS) treatments on the olfactory performance of patients with treatment refractory Major Depressive Disorder (MDD) and bipolar depression. ECT has been identified as today's most effective treatment for severe depression due to the remission rates, speed of response, and the completeness of remission. iTBS is a new remittent transcranial magnetic stimulation (rTMS) protocol that has gained more notoriety within the field for the speed of administration, effectiveness of the treatment, and speed of response. Unlike rTMS, TBS mimics the endogenous theta rhythms of the brain, which results in greater potency in inducing long-term potentiation of synaptic connections in the targeted brain regions. iTBS has been shown to be effective in treating mood disturbances, and increasing plasticity and inducing neurogenesis in patients. People with MDD often struggle with cognitive impairments such as decreased executive functioning, attention, concentration, speed of processing, and working memory. The brain areas associated with cognition, such as the prefrontal cortex and hippocampus are negatively affected by depression; studies have shown decreased volume, activity, and disturbed brain connectivity in those two areas. Currently, there is a lack of treatment options for improving cognition in depressed patients. The investigators are focussing on exploring the therapeutic potential of iTBS on cognition.The preliminary evidence from our study will add to scientists' understanding of the short and long term effects of iTBS treatment on the cognitive related areas in the brain through the use of fMRI. The investigators also hope our research will allow psychiatrists to deliver better care to patients with debilitating cognitive impairments associated with depression. Overall, a study examining the olfactory and cognitive performance of patients with treatment resistant MDD and bipolar depression, pre-ECT/iTBS, post-ECT/iTBS, and post-remission would yield valuable insight into the link between olfaction and mood disorders as well as cognition and mood disorders.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Depression

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Patient

Patients will be receiving either ECT or iTBS as a depression management. Olfactory functioning will be assessed at pre-treatment and 6 weeks later at post-treatment using Sniffin Sticks. Cognition will also be tested using Cognitive Function Imaging and Battery in the fMRI as well as Cognitive Batteries outside of the scanner at pre-treatment, 6 weeks later at post-treatment, and 3 months after the final treatment session.

Cognitive Function Imaging and Battery

Intervention Type DEVICE

Individuals will be placed in the fMRI scanner and complete the NBACK Cognitive Task

Sniffin Sticks

Intervention Type DEVICE

Using Sniffin Sticks, olfactory functioning will be assessed using three tests: identification, discrimination, and threshold.

Cognitive Batteries

Intervention Type OTHER

Participants will conduct the following cognitive batteries: DSST, TMT A \& B, RAVLT

Control

Controls will have their olfactory functioning assessed at baseline and 6 weeks after the baseline assessment using Sniffin Sticks. Cognition will also be tested using Cognitive Function Imaging and Battery in the fMRI as well as Cognitive Batteries outside of the scanner at pre-treatment, 6 weeks later at post-treatment, and 3 months after the final treatment session.

Cognitive Function Imaging and Battery

Intervention Type DEVICE

Individuals will be placed in the fMRI scanner and complete the NBACK Cognitive Task

Sniffin Sticks

Intervention Type DEVICE

Using Sniffin Sticks, olfactory functioning will be assessed using three tests: identification, discrimination, and threshold.

Cognitive Batteries

Intervention Type OTHER

Participants will conduct the following cognitive batteries: DSST, TMT A \& B, RAVLT

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Cognitive Function Imaging and Battery

Individuals will be placed in the fMRI scanner and complete the NBACK Cognitive Task

Intervention Type DEVICE

Sniffin Sticks

Using Sniffin Sticks, olfactory functioning will be assessed using three tests: identification, discrimination, and threshold.

Intervention Type DEVICE

Cognitive Batteries

Participants will conduct the following cognitive batteries: DSST, TMT A \& B, RAVLT

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Signed Patient Informed Consent
* Patients with MDD (DSM-IV-TR - criteria used) OR Patients with bipolar depression (DSM-IV-TR - criteria used)
* Males or females over 18 years of age
* In-patients or out-patients currently scheduled to receive ECT or rTMS

Exclusion Criteria

* Patients suffering from other neurological or endocrine disorders known to affect olfactory functioning.
* Patients suffering from a respiratory tract infection or other respiratory disorder known to affect olfactory functioning at investigator's discretion
* Schizophrenia, Schizoaffective or other Psychotic Disorder
* Patients over 65 years of age
* Patients with significant allergies
* Patients with environmental sensitivities (e.g. perfumes)
* Patients with mechanical obstruction of the nasal passages (e.g. deviated septum)
* Patients with congenital anosmia or other previous primary olfactory dysfunction
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Providence Healthcare

OTHER

Sponsor Role collaborator

Queen's University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Dr. Roumen Milev

Dr. Roumen Milev

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Roumen V Milev, MD FRCPC

Role: PRINCIPAL_INVESTIGATOR

Queen's University Department of Psychiatry

References

Explore related publications, articles, or registry entries linked to this study.

Ludvigson, H.W., & Rottman, T.R. (1989). Effects of ambient odours of lavender and cloves on cognition, memory, affect, and mood. Chemical Senses, 14(4), 525-536.

Reference Type BACKGROUND

Albrecht J, Wiesmann M. [The human olfactory system. Anatomy and physiology]. Nervenarzt. 2006 Aug;77(8):931-9. doi: 10.1007/s00115-006-2121-z. German.

Reference Type BACKGROUND
PMID: 16871378 (View on PubMed)

Amsterdam JD, Settle RG, Doty RL, Abelman E, Winokur A. Taste and smell perception in depression. Biol Psychiatry. 1987 Dec;22(12):1481-5. doi: 10.1016/0006-3223(87)90108-9. No abstract available.

Reference Type BACKGROUND
PMID: 3676376 (View on PubMed)

Austin MP, Mitchell P, Goodwin GM. Cognitive deficits in depression: possible implications for functional neuropathology. Br J Psychiatry. 2001 Mar;178:200-6. doi: 10.1192/bjp.178.3.200.

Reference Type BACKGROUND
PMID: 11230029 (View on PubMed)

Berendse HW, Ponsen MM. Detection of preclinical Parkinson's disease along the olfactory trac(t). J Neural Transm Suppl. 2006;(70):321-5. doi: 10.1007/978-3-211-45295-0_48.

Reference Type BACKGROUND
PMID: 17017547 (View on PubMed)

Brand G, Millot JL, Henquell D. Complexity of olfactory lateralization processes revealed by functional imaging: a review. Neurosci Biobehav Rev. 2001 Mar;25(2):159-66. doi: 10.1016/s0149-7634(01)00005-7.

Reference Type BACKGROUND
PMID: 11323080 (View on PubMed)

Castaneda AE, Tuulio-Henriksson A, Marttunen M, Suvisaari J, Lonnqvist J. A review on cognitive impairments in depressive and anxiety disorders with a focus on young adults. J Affect Disord. 2008 Feb;106(1-2):1-27. doi: 10.1016/j.jad.2007.06.006. Epub 2007 Aug 20.

Reference Type BACKGROUND
PMID: 17707915 (View on PubMed)

Doty RL, Shaman P, Dann M. Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav. 1984 Mar;32(3):489-502. doi: 10.1016/0031-9384(84)90269-5.

Reference Type BACKGROUND
PMID: 6463130 (View on PubMed)

Drevets WC. Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression. Prog Brain Res. 2000;126:413-31. doi: 10.1016/S0079-6123(00)26027-5.

Reference Type BACKGROUND
PMID: 11105660 (View on PubMed)

Frodl T, Meisenzahl EM, Zetzsche T, Born C, Groll C, Jager M, Leinsinger G, Bottlender R, Hahn K, Moller HJ. Hippocampal changes in patients with a first episode of major depression. Am J Psychiatry. 2002 Jul;159(7):1112-8. doi: 10.1176/appi.ajp.159.7.1112.

Reference Type BACKGROUND
PMID: 12091188 (View on PubMed)

Fung PK, Robinson PA. Neural field theory of synaptic metaplasticity with applications to theta burst stimulation. J Theor Biol. 2014 Jan 7;340:164-76. doi: 10.1016/j.jtbi.2013.09.021. Epub 2013 Sep 21.

Reference Type BACKGROUND
PMID: 24060620 (View on PubMed)

Gentner R, Wankerl K, Reinsberger C, Zeller D, Classen J. Depression of human corticospinal excitability induced by magnetic theta-burst stimulation: evidence of rapid polarity-reversing metaplasticity. Cereb Cortex. 2008 Sep;18(9):2046-53. doi: 10.1093/cercor/bhm239. Epub 2007 Dec 28.

Reference Type BACKGROUND
PMID: 18165282 (View on PubMed)

Golinkoff M, Sweeney JA. Cognitive impairments in depression. J Affect Disord. 1989 Sep-Oct;17(2):105-12. doi: 10.1016/0165-0327(89)90032-3.

Reference Type BACKGROUND
PMID: 2527885 (View on PubMed)

Gross-Isseroff R, Luca-Haimovici K, Sasson Y, Kindler S, Kotler M, Zohar J. Olfactory sensitivity in major depressive disorder and obsessive compulsive disorder. Biol Psychiatry. 1994 May 15;35(10):798-802. doi: 10.1016/0006-3223(94)91142-8.

Reference Type BACKGROUND
PMID: 8043710 (View on PubMed)

Hawkes C. Olfaction in neurodegenerative disorder. Mov Disord. 2003 Apr;18(4):364-72. doi: 10.1002/mds.10379.

Reference Type BACKGROUND
PMID: 12671941 (View on PubMed)

Kellner CH, Fink M. The efficacy of ECT and "treatment resistance". J ECT. 2002 Mar;18(1):1-2. doi: 10.1097/00124509-200203000-00001. No abstract available.

Reference Type BACKGROUND
PMID: 11925510 (View on PubMed)

Lombion-Pouthier S, Vandel P, Nezelof S, Haffen E, Millot JL. Odor perception in patients with mood disorders. J Affect Disord. 2006 Feb;90(2-3):187-91. doi: 10.1016/j.jad.2005.11.012. Epub 2005 Dec 27.

Reference Type BACKGROUND
PMID: 16376994 (View on PubMed)

Martzke JS, Kopala LC, Good KP. Olfactory dysfunction in neuropsychiatric disorders: review and methodological considerations. Biol Psychiatry. 1997 Oct 15;42(8):721-32. doi: 10.1016/s0006-3223(96)00442-8. No abstract available.

Reference Type BACKGROUND
PMID: 9325566 (View on PubMed)

Negoias S, Croy I, Gerber J, Puschmann S, Petrowski K, Joraschky P, Hummel T. Reduced olfactory bulb volume and olfactory sensitivity in patients with acute major depression. Neuroscience. 2010 Aug 11;169(1):415-21. doi: 10.1016/j.neuroscience.2010.05.012. Epub 2010 May 13.

Reference Type BACKGROUND
PMID: 20472036 (View on PubMed)

Pause BM, Miranda A, Goder R, Aldenhoff JB, Ferstl R. Reduced olfactory performance in patients with major depression. J Psychiatr Res. 2001 Sep-Oct;35(5):271-7. doi: 10.1016/s0022-3956(01)00029-2.

Reference Type BACKGROUND
PMID: 11591429 (View on PubMed)

Plewnia C, Pasqualetti P, Grosse S, Schlipf S, Wasserka B, Zwissler B, Fallgatter A. Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. J Affect Disord. 2014 Mar;156:219-23. doi: 10.1016/j.jad.2013.12.025. Epub 2013 Dec 28.

Reference Type BACKGROUND
PMID: 24411682 (View on PubMed)

Rolls ET, Kringelbach ML, de Araujo IE. Different representations of pleasant and unpleasant odours in the human brain. Eur J Neurosci. 2003 Aug;18(3):695-703. doi: 10.1046/j.1460-9568.2003.02779.x.

Reference Type BACKGROUND
PMID: 12911766 (View on PubMed)

Satoh S, Morita N, Matsuzaki I, Konishi T, Nakano T, Minoshita S, Arizono H, Saito S, Ayabe AS. Relationship between odor perception and depression in the Japanese elderly. Psychiatry Clin Neurosci. 1996 Oct;50(5):271-5. doi: 10.1111/j.1440-1819.1996.tb00563.x.

Reference Type BACKGROUND
PMID: 9201790 (View on PubMed)

Seo HS, Jeon KJ, Hummel T, Min BC. Influences of olfactory impairment on depression, cognitive performance, and quality of life in Korean elderly. Eur Arch Otorhinolaryngol. 2009 Nov;266(11):1739-45. doi: 10.1007/s00405-009-1001-0. Epub 2009 Jun 2.

Reference Type BACKGROUND
PMID: 19488777 (View on PubMed)

Serby M, Larson P, Kalkstein D. Olfactory sense in psychoses. Biol Psychiatry. 1990 Nov 1;28(9):830. doi: 10.1016/0006-3223(90)90520-c. No abstract available.

Reference Type BACKGROUND
PMID: 2257290 (View on PubMed)

Small DM, Jones-Gotman M, Zatorre RJ, Petrides M, Evans AC. Flavor processing: more than the sum of its parts. Neuroreport. 1997 Dec 22;8(18):3913-7. doi: 10.1097/00001756-199712220-00014.

Reference Type BACKGROUND
PMID: 9462465 (View on PubMed)

Snaith RP, Hamilton M, Morley S, Humayan A, Hargreaves D, Trigwell P. A scale for the assessment of hedonic tone the Snaith-Hamilton Pleasure Scale. Br J Psychiatry. 1995 Jul;167(1):99-103. doi: 10.1192/bjp.167.1.99.

Reference Type BACKGROUND
PMID: 7551619 (View on PubMed)

Steiner JE, Lidar-Lifschitz D, Perl E. Taste and odor: reactivity in depressive disorders, a multidisciplinary approach. Percept Mot Skills. 1993 Dec;77(3 Pt 2):1331-46. doi: 10.2466/pms.1993.77.3f.1331.

Reference Type BACKGROUND
PMID: 8170789 (View on PubMed)

Swiecicki L, Zatorski P, Bzinkowska D, Sienkiewicz-Jarosz H, Szyndler J, Scinska A. Gustatory and olfactory function in patients with unipolar and bipolar depression. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Aug 1;33(5):827-34. doi: 10.1016/j.pnpbp.2009.03.030. Epub 2009 Apr 5.

Reference Type BACKGROUND
PMID: 19345708 (View on PubMed)

Van Toller S, Reed MK. Brain electrical activity topographical maps produced in response to olfactory and chemosensory stimulation. Psychiatry Res. 1989 Sep;29(3):429-30. doi: 10.1016/0165-1781(89)90112-1. No abstract available.

Reference Type BACKGROUND
PMID: 2608810 (View on PubMed)

Warner MD, Peabody CA, Csernansky JG. Olfactory functioning in schizophrenia and depression. Biol Psychiatry. 1990 Feb 15;27(4):457-8. doi: 10.1016/0006-3223(90)90557-i. No abstract available.

Reference Type BACKGROUND
PMID: 2178695 (View on PubMed)

Weismann M, Yousry I, Heuberger E, Nolte A, Ilmberger J, Kobal G, Yousry TA, Kettenmann B, Naidich TP. Functional magnetic resonance imaging of human olfaction. Neuroimaging Clin N Am. 2001 May;11(2):237-50, viii.

Reference Type BACKGROUND
PMID: 11489737 (View on PubMed)

Wiesmann M, Kopietz R, Albrecht J, Linn J, Reime U, Kara E, Pollatos O, Sakar V, Anzinger A, Fesl G, Bruckmann H, Kobal G, Stephan T. Eye closure in darkness animates olfactory and gustatory cortical areas. Neuroimage. 2006 Aug 1;32(1):293-300. doi: 10.1016/j.neuroimage.2006.03.022. Epub 2006 May 2.

Reference Type BACKGROUND
PMID: 16631383 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

6006093

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Theta-Burst Stimulation to Treat Depression
NCT07033780 RECRUITING PHASE1