Panic DisorderNCT04029740
Exosomal microRNAs as a Biomarker in Panic Disorder and in Response to CBT
A study testing CBT- both internet and face to face in people with Panic Disorder, run by Hebrew University of Jerusalem at 1 site in Israel.
Trial summary
Cognitive behavior therapy (CBT) has long been known as an effective treatment for anxiety disorders, either when given by a therapist or when self-administered through a computer program. However, the biological effect of CBT remained largely unexplored. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Panic Disorder
- What is being tested?
- CBT- both internet and face to face
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteIsrael
- Study dates
- 19 May 2019to 23 Apr 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Principal DSM-5 primary diagnosis of panic disorder and/or agoraphobia.
- 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.
Who cannot join
- Substance abuse or dependence within the last 6 months.
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Searching for Exosomal microRNAs and Cellular Biomarkers and Mechanisms Underlying the Differences Between Panic Disorder Patients Who Are Responders and Non-responders to Cognitive Behavior Therapy
Cognitive behavior therapy (CBT) has long been known as an effective treatment for anxiety disorders, either when given by a therapist or when self-administered through a computer program. However, the biological effect of CBT remained largely unexplored. Most studies focused on genomic differences and pursued differences in methylation patterns following CBT, but the findings were very limited in scope, especially when comparing responders and non-responders to CBT. In the currently proposed study, the investigators plan to go one step further and look for changes in exosomal microRNAs (miRs) from serum samples taken before and after CBT from Panic Disorder (PD) patients. Notably, miR changes show a much faster biological response than methylation patterns yet had never been used before in PD research. The primary benefit of this work will be in providing biological validation to psychological treatments. PD is a heavy public health burden, associated with significant market potential for both therapeutic and diagnostic uses.
Read the detailed description
Cognitive Behavior Therapy (CBT) is an evidence-based treatment, commonly used for treating anxiety disorders. Patients with anxiety disorders are characterized by having cognitive distortions regarding evaluations of threat, which results in safety behaviors to avoid them thereby causing impairment in the patient's quality of life. CBT focuses on changing those "false beliefs" and "maladaptive behaviors" by exposing the patients to their anxiety source in a gradual way, supervised by the therapist.
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
- Panic Disorder
- Being tested
- CBT- both internet and face to face, No intervention
- Medical subject headings
- Panic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CBT- both internet and face to faceBehavioural
Also called Cognitive behavioral therapy for panic disorder
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 interventionOther
Healthy controls will not receive any intervention.
| Study group | Role | What they receive |
|---|---|---|
| Healthy controls | Other | 40 Healthy controls matched on gender and age with no current psychopathology will have exosomal microRNAs measured twice over a 3 month period. Receives: Other: No intervention |
| panic disorder receiving CBT | Experimental | 40 adult patients diagnosed with primary panic disorder will have their exosomal microRNAs measured 2x over 3 months. Receives: Behavioral: CBT- both internet and face to face |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differntial expression of plasma exosomal microRNAs
Exosomes are a type of extracellular vesicles of endocytic origin, used in signalling 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. Will be measured twice: pre and post treatment (post or 6 months, whichever is later, to the maximum of 6 months).
Measured: Pre and post treatment, up to 6 months apart.
Secondary outcomes (7)
Change in Panic Disorder Severity Scale (PDSS)
Independent evaluators will conduct pre and post treatment evaluations and self report will be administered weekly. The PDSS can be administered as an interview or self-report measure. It is comprised of 7 items that are scored from 0-4, with a total scale score ranging from 0-28. Higher scores mean more severe panic disorder symptoms. Will be administered weekly during treatment, plus at pre and post treatment evaluations.
Measured: Weekly during treatment and at pre and post treatment evaluations, up to 6 months apart.
Change in Anxiety Sensitivity Index-3 (ASI-3)
The ASI-3 is an 18-item self-report measure that measures beliefs regarding panic related bodily sensations. It will be used as a total score, which ranges from 0-72. The ASI-3 will be administered weekly. Higher scores mean more severe anxiety sensitivity.
Measured: Weekly during treatment and at pre and post treatment evaluations, up to 6 months apart.
Change in Mobility Inventory
The Mobility Inventory is a self report measure of agoraphobic avoidance in which patients are asked to rate how much they avoid 26 situations on a 1-5 scale twice, once when alone and a second time when accompanied. The average score of all times will be used, which will range from 1-5. The MI will be administered weekly.
Measured: Weekly during treatment and at pre and post treatment evaluations, up to 6 months apart.
Differntial expression of whole Blood short non-coding RNAs
We will also collect whole blood samples that will serve as a secondary outcome measurement, checking for changes in expression of small non-coding circulating RNAs as well. This measurement will act as a more clinically accessible balance for the exosomes approach. Will be measured twice: pre and post treatment (post or 3 months, whichever is later, to the maximum of 6 months).
Measured: Pre and post treatment, up to 6 months apart.
Change in the Five-Dimensional Curiosity Scale (DCS-5)
The DCS-5 is a self-report measure that measures 5 dimensions of curiosity via 25 items which are rated on a 1-7 scale. The total score of all 25 (ranging from 25-175) items and 5 subscales (each ranging from 5-35) will be used for this study. Will be measured twice: pre and post treatment (post or 6 months, whichever is later, to the maximum of 6 months).
Measured: Pre and post treatment, up to 6 months apart.
Changes in Experiences in Close Relationship Scale-Short (ECR-s)
The ECR-s is a brief self report instrument that measures both Anxious and avoidance adult attachment styles. The two scales each contain 6 items rated on a 1-7 scale that are summed for each subscale, ranging from 6-42. Will be measured twice: pre and post treatment (post or 6 months, whichever is later, to the maximum of 6 months).
Measured: Pre and post treatment, up to 6 months apart.
Changes in Sexual Functioning Questionnaire
this is a self-report measure of sexual functioning that is comprised of 14 items that are rated on a 1-5 scale and scored by a sum score that ranges between 14-70. Higher scores mean better sexual functioning. Will be measured twice: pre and post treatment (post or 6 months, whichever is later, to the maximum of 6 months).
Measured: Pre and post treatment, up to 6 months apart.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2019
- Study start19 May 2019
- Primary completion23 Apr 2023
- Study completion23 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Panic DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- All patients will be treated with either internet or face to face CBT according to their preference. Circulating exosomal microRNAs will be measured pretreatment and post-treatment.
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hebrew University of Jerusalem
- Sponsor type
- University, hospital or other
- Collaborators
- Hadassah Medical Organization
- Responsible party
- Principal investigator, Jonathan D. Huppert, Hebrew University of Jerusalem
- Investigators
- Hermona Soreq, Professor, Principal investigator, Hebrew University of JerusalemRonen Segman, Professor, Principal investigator, Hadassah Hebrew University HospitalSalomon Israel, Professor, Principal investigator, Hebrew University of Jerusalem
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04029740
- Sponsor's protocol ID
- 0577-18-HMO
- Status last verified
- Feb 2021
- First submitted
- 22 May 2019
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in a publication will be placed on a public website after the manuscript is submitted for publication.
Publications
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.
PubMed 26084661Andersson 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.
PubMed 25273302Bekenstein 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.
PubMed 28584127Barlow DH. Cognitive-behavioral therapy for panic disorder: current status. J Clin Psychiatry. 1997;58 Suppl 2:32-6; discussion 36-7.
PubMed 9078992Fruhbeis 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.
PubMed 26142461Huppert, 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.
PubMed 23034410Olthuis 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.
PubMed 26968204Roberts 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.
PubMed 25226553Ziegler 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.
PubMed 27045843Strawn 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.
PubMed 29588049
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Searching for Exosomal microRNAs and Cellular Biomarkers and Mechanisms Underlying the Differences Between Panic Disorder Patients Who Are Responders and Non-responders to Cognitive Behavior Therapy
- ClinicalTrials.gov ID
- NCT04029740
- Acronym / sponsor ID
- 0577-18-HMO
- Conditions
- Panic Disorder
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Hebrew University of JerusalemUniversity, hospital or other
- Collaborators
- Hadassah Medical Organization
- Study start
- 19 May 2019 (actual)
- Primary completion
- 23 Apr 2023 (actual)
- Study completion
- 23 Apr 2023 (actual)
- First posted
- 23 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cognitive behavior therapy (CBT) has long been known as an effective treatment for anxiety disorders, either when given by a therapist or when self-administered through a computer program. However, the biological effect of CBT remained largely unexplored. Most studies focused on genomic differences and pursued differences in methylation patterns following CBT, but the findings were very limited in scope, especially when comparing responders and non-responders to CBT. In the currently proposed study, the investigators plan to go one step further and look for changes in exosomal microRNAs (miRs) from serum samples taken before and after CBT from Panic Disorder (PD) patients. Notably, miR changes show a much faster biological response than methylation patterns yet had never been used before in PD research. The primary benefit of this work will be in providing biological validation to psychological treatments. PD is a heavy public health burden, associated with significant market potential for both therapeutic and diagnostic uses.
Detailed description
Cognitive Behavior Therapy (CBT) is an evidence-based treatment, commonly used for treating anxiety disorders. Patients with anxiety disorders are characterized by having cognitive distortions regarding evaluations of threat, which results in safety behaviors to avoid them thereby causing impairment in the patient's quality of life. CBT focuses on changing those "false beliefs" and "maladaptive behaviors" by exposing the patients to their anxiety source in a gradual way, supervised by the therapist.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- All patients will be treated with either internet or face to face CBT according to their preference. Circulating exosomal microRNAs will be measured pretreatment and post-treatment.
| Arm | Type | Receives |
|---|---|---|
| Healthy controls | Other | Other: No intervention40 Healthy controls matched on gender and age with no current psychopathology will have exosomal microRNAs measured twice over a 3 month period. |
| panic disorder receiving CBT | Experimental | Behavioral: CBT- both internet and face to face40 adult patients diagnosed with primary panic disorder will have their exosomal microRNAs measured 2x over 3 months. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Principal DSM-5 primary diagnosis of panic disorder and/or agoraphobia.
- 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.
Key exclusion criteria (5 listed)
- Substance abuse or dependence within the last 6 months.
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CBT- both internet and face to faceAlso: Cognitive behavioral therapy for panic disorderThere 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. | Behavioural | panic disorder receiving CBT |
| No interventionHealthy controls will not receive any intervention. | Other | Healthy controls |
Primary outcome
Differntial expression of plasma exosomal microRNAs
Time frame: Pre and post treatment, up to 6 months apart.
Exosomes are a type of extracellular vesicles of endocytic origin, used in signalling 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. Will be measured twice: pre and post treatment (post or 6 months, whichever is later, to the maximum of 6 months).
7 secondary outcomes
Change in Panic Disorder Severity Scale (PDSS)
Time frame: Weekly during treatment and at pre and post treatment evaluations, up to 6 months apart.
Change in Anxiety Sensitivity Index-3 (ASI-3)
Time frame: Weekly during treatment and at pre and post treatment evaluations, up to 6 months apart.
Change in Mobility Inventory
Time frame: Weekly during treatment and at pre and post treatment evaluations, up to 6 months apart.
Differntial expression of whole Blood short non-coding RNAs
Time frame: Pre and post treatment, up to 6 months apart.
Change in the Five-Dimensional Curiosity Scale (DCS-5)
Time frame: Pre and post treatment, up to 6 months apart.
Changes in Experiences in Close Relationship Scale-Short (ECR-s)
Time frame: Pre and post treatment, up to 6 months apart.
Changes in Sexual Functioning Questionnaire
Time frame: Pre and post treatment, up to 6 months apart.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
- Background: PubMed 26084661Alexander 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.
- Background: PubMed 25273302Andersson 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.
- Background: PubMed 28584127Bekenstein 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.
- Background: PubMed 9078992Barlow DH. Cognitive-behavioral therapy for panic disorder: current status. J Clin Psychiatry. 1997;58 Suppl 2:32-6; discussion 36-7.
- Background: PubMed 26142461Fruhbeis 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.
- BackgroundHuppert, 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.
- Background: PubMed 23034410Meunier 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.
- Background: PubMed 26968204Olthuis 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.
- Background: PubMed 25226553Roberts 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.
- Background: PubMed 27045843Ziegler 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.
- Background: PubMed 29588049Strawn 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.
- Individual participant dataSharing planned: Yes. All IPD that underlie results in a publication will be placed on a public website after the manuscript is submitted for publication.
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Not yet recruiting
Effectiveness of Internet-based Unified Protocol (iUP) for Emotional Problems: A Randomized Controlled Trial
Depression - Major Depressive Disorder, Generalised Anxiety Disorder
Not yet recruiting
A Clinical Trial to Evaluate the Efficacy and Safety of Meltz, a Digital Therapeutic Device, for Improving Panic Symptoms in Patients With Panic Disorder
Panic Disorder, Agoraphobia
Not yet recruiting
The Effect of Bitewing Radiography on Outcomes and Costs of Treating Caries in Permanent Teeth
Dental Caries, Teeth Loss
Active, not recruiting
Evaluation of Family-Based Behavioral Treatments for Youth With Anxiety and Obsessive-Compulsive Disorder
Obsessive-Compulsive Disorder in Children, Anxiety Disorder of Childhood
Recruiting
Qigong and Multicomponent Exercise in Panic Disorder
Panic Disorder, Panic Disorder (With or Without Agoraphobia)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hermona Soreq, Professor principal investigator
Hebrew University of Jerusalem
Ronen Segman, Professor principal investigator
Hadassah Hebrew University Hospital
Salomon Israel, Professor principal investigator
Hebrew University of Jerusalem
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CBT- both internet and face to face in people with Panic Disorder, run by Hebrew University of Jerusalem at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differntial expression of plasma exosomal microRNAs (time frame: Pre and post treatment, up to 6 months apart.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04029740, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2026.