Exosomal microRNAs as a Biomarker in Panic Disorder and in Response to CBT
NCT ID: NCT04029740
Last Updated: 2021-02-09
Study Results
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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UNKNOWN
NA
80 participants
INTERVENTIONAL
2019-03-24
2021-12-24
Brief Summary
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Detailed Description
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Anxiety disorders are relatively common, and many people have difficulty accessing treatment due to a variety of obstacles. Researchers have therefore explored the possibility of using different methods to administer CBT, resulting in the making of internet-delivered CBT (iCBT). iCBT programs can involve therapist guidance through emails or can be entirely unguided. These programs are typically comprised of 6-15 modules, which are text chapters corresponding to sessions in face-to-face therapy. These programs require little therapist involvement other than guidance and feedback on homework assignments. Current meta-analyses suggest that iCBT does not differ from regular CBT in its efficacy, conducted through a guided program.
In this study, the investigators plan to examine whether iCBT and regular CBT can cause biological changes as well as cognitive ones. Few previous studies have shown epigenetic changes in different directions for CBT responders and non-responders. Those studies used methylation patterns as biomarkers, showing that Panic Disorder (PD) patients had lower methylation in specific genes than the control group at the baseline point. After going through CBT the responders showed higher methylation and the non-responders showed even lower methylation than at the baseline point. In addition, a more recent study showed that in comparison to healthy controls, PD patients showed changes in immune system activities. Microglial acid sensing G-protein coupled receptor and T cell death-associated gene-8 (TDAG8), which was found was found higher in PD patients.
The investigators wish to take these findings one step forward by using micro-RNAs (miRs) content of circulation exosomes as our biomarker. Exosomes are a type of extracellular vesicles of endocytic origin, used in signaling and cell to cell communication, by transferring proteins, lipids, and variety of RNAs between cells. miRs are short single-stranded RNA molecules that bind to complementary sequences of target mRNAs, causing inhibition of their translation and/or inducing target degradation and affecting brain functioning and mental processes.
The investigators will base their work on the hypothesis that the brain's state is reflected, to a certain extent in the miR contents of circulating exosomes. Therefore, the aim of the study will be to test the difference between patients and controls as well as between responders and non-responders by profiling miRs content of circulation exosomes from their plasma samples and seeking association with their clinical data. Whole blood samples will also be collected, in order to serve as secondary outcome measurement, checking for changes in expression of other small non-coding circulating RNAs as well.
The investigators will use a cohort of 40 panic disorder patients, comparing them with matching 40 mentally healthy controls. This approach has never been used before in the field of anxiety biomarkers, although miR changes show a much faster biological response than methylation patterns. Therefore, the investigators believe it will provide many new insights on the biological changes following PD and its treatment using CBT/iCBT, especially regarding the biological difference between respondents and non-respondents.
The investigators anticipate big benefits for psychologists and psychiatrists who could in the future use simple blood samples to determine which kind of therapy will be most suitable for their patients, or rather to check if the therapy has given the desirable outcomes. Biotech firms may be interested in developing this method as a commercial diagnostic tool that could easily be used by health maintenance organizations just as a simple blood test. PD is a big public health burden, leading the market potential both for therapeutics as well as diagnostics to be large in dollar terms.
This study received two ethics approvals that act together. The mentioned ethics approval given by the Hebrew university ethics committee was given for the psychological part of the experiment and include the CBT, using a psychologist or computer program. A second approval, Helsinki approval by the Hadassah hospital committee, covers the biological part of the experiment - including the blood drawing and further analysis.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
BASIC_SCIENCE
NONE
Study Groups
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Healthy controls
40 Healthy controls matched on gender and age with no current psychopathology will have exosomal microRNAs measured twice over a 3 month period.
No intervention
Healthy controls will not receive any intervention.
panic disorder receiving CBT
40 adult patients diagnosed with primary panic disorder will have their exosomal microRNAs measured 2x over 3 months.
CBT- both internet and face to face
There are a few common psychotherapies for treating PD, with Cognitive Behavioral Therapy (CBT) as the most common. The most known type of CBT for treating PD consists of two major strategies: cognitive restructuring, and interoceptive and structured exposure to bodily sensations that have become associated with panic attacks (D H Barlow, 1997). The ICBT therapy is based on Barlow and Craske's (2007) protocol for treating PD with elaborations (Huppert \& Baker-Morissette, 2003). It includes six modules containing psychoeducation, cognitive restructuring, exposures, acceptance, and consolidation of gains and relapse prevention. The online modules include reading passages, worksheets, videos, and homework assignments. After completing each module, participants practice related skills and complete homework assignments. The treatment is up to 16 weeks long; participants are encouraged to complete the treatment within this time period, and reminders are sent to monitor their progress.
Interventions
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CBT- both internet and face to face
There are a few common psychotherapies for treating PD, with Cognitive Behavioral Therapy (CBT) as the most common. The most known type of CBT for treating PD consists of two major strategies: cognitive restructuring, and interoceptive and structured exposure to bodily sensations that have become associated with panic attacks (D H Barlow, 1997). The ICBT therapy is based on Barlow and Craske's (2007) protocol for treating PD with elaborations (Huppert \& Baker-Morissette, 2003). It includes six modules containing psychoeducation, cognitive restructuring, exposures, acceptance, and consolidation of gains and relapse prevention. The online modules include reading passages, worksheets, videos, and homework assignments. After completing each module, participants practice related skills and complete homework assignments. The treatment is up to 16 weeks long; participants are encouraged to complete the treatment within this time period, and reminders are sent to monitor their progress.
No intervention
Healthy controls will not receive any intervention.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Aged 18 years or older.
* PD duration of at least 3 months.
* If participant is on on medications for PD, the dosage has to remain constant for 3 months prior to the start of treatment and cannot be increased during treatment.
* The participant must have access to the internet and be willing to use it.
Exclusion Criteria
* Active suicide potential within the last 6 months.
* Any current or history of psychosis or bipolar I disorder.
* Currently in weekly or biweekly psychotherapy.
* History of a complete course of panic focused CBT
18 Years
65 Years
ALL
Yes
Sponsors
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Hadassah Medical Organization
OTHER
Hebrew University of Jerusalem
OTHER
Responsible Party
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Jonathan D. Huppert
Professor
Principal Investigators
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Hermona Soreq, Professor
Role: PRINCIPAL_INVESTIGATOR
Hebrew University of Jerusalem
Ronen Segman, Professor
Role: PRINCIPAL_INVESTIGATOR
Hadassah Hebrew University Hospital
Salomon Israel, Professor
Role: PRINCIPAL_INVESTIGATOR
Hebrew University of Jerusalem
Locations
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Hebrew University of Jerusalem
Jerusalem, , Israel
Countries
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Central Contacts
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Facility Contacts
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References
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Alexander M, Hu R, Runtsch MC, Kagele DA, Mosbruger TL, Tolmachova T, Seabra MC, Round JL, Ward DM, O'Connell RM. Exosome-delivered microRNAs modulate the inflammatory response to endotoxin. Nat Commun. 2015 Jun 18;6:7321. doi: 10.1038/ncomms8321.
Andersson G, Cuijpers P, Carlbring P, Riper H, Hedman E. Guided Internet-based vs. face-to-face cognitive behavior therapy for psychiatric and somatic disorders: a systematic review and meta-analysis. World Psychiatry. 2014 Oct;13(3):288-95. doi: 10.1002/wps.20151.
Bekenstein U, Mishra N, Milikovsky DZ, Hanin G, Zelig D, Sheintuch L, Berson A, Greenberg DS, Friedman A, Soreq H. Dynamic changes in murine forebrain miR-211 expression associate with cholinergic imbalances and epileptiform activity. Proc Natl Acad Sci U S A. 2017 Jun 20;114(25):E4996-E5005. doi: 10.1073/pnas.1701201114. Epub 2017 Jun 5.
Barlow DH. Cognitive-behavioral therapy for panic disorder: current status. J Clin Psychiatry. 1997;58 Suppl 2:32-6; discussion 36-7.
Fruhbeis C, Helmig S, Tug S, Simon P, Kramer-Albers EM. Physical exercise induces rapid release of small extracellular vesicles into the circulation. J Extracell Vesicles. 2015 Jul 2;4:28239. doi: 10.3402/jev.v4.28239. eCollection 2015.
Huppert, J. D., & Baker-Morissette, S. L. (2003). Beyond the manual: The insider's guide to panic control treatment. Cognitive and Behavioral Practice, 10(1), 2-13.
Meunier J, Lemoine F, Soumillon M, Liechti A, Weier M, Guschanski K, Hu H, Khaitovich P, Kaessmann H. Birth and expression evolution of mammalian microRNA genes. Genome Res. 2013 Jan;23(1):34-45. doi: 10.1101/gr.140269.112. Epub 2012 Oct 3.
Olthuis JV, Watt MC, Bailey K, Hayden JA, Stewart SH. Therapist-supported Internet cognitive behavioural therapy for anxiety disorders in adults. Cochrane Database Syst Rev. 2016 Mar 12;3(3):CD011565. doi: 10.1002/14651858.CD011565.pub2.
Roberts S, Lester KJ, Hudson JL, Rapee RM, Creswell C, Cooper PJ, Thirlwall KJ, Coleman JR, Breen G, Wong CC, Eley TC. Serotonin transporter [corrected] methylation and response to cognitive behaviour therapy in children with anxiety disorders. Transl Psychiatry. 2014 Sep 16;4(9):e444. doi: 10.1038/tp.2014.83.
Ziegler C, Richter J, Mahr M, Gajewska A, Schiele MA, Gehrmann A, Schmidt B, Lesch KP, Lang T, Helbig-Lang S, Pauli P, Kircher T, Reif A, Rief W, Vossbeck-Elsebusch AN, Arolt V, Wittchen HU, Hamm AO, Deckert J, Domschke K. MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy. Transl Psychiatry. 2016 Apr 5;6(4):e773. doi: 10.1038/tp.2016.41.
Strawn JR, Mills JA, Sauley BA, Welge JA. The Impact of Antidepressant Dose and Class on Treatment Response in Pediatric Anxiety Disorders: A Meta-Analysis. J Am Acad Child Adolesc Psychiatry. 2018 Apr;57(4):235-244.e2. doi: 10.1016/j.jaac.2018.01.015. Epub 2018 Feb 8.
Other Identifiers
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0577-18-HMO
Identifier Type: -
Identifier Source: org_study_id
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