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Exosomal microRNAs as a Biomarker in Panic Disorder and in Response to CBT

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ClinicalTrials.gov Identifier: NCT04029740
Recruitment Status : Recruiting
First Posted : July 23, 2019
Last Update Posted : July 23, 2019
Sponsor:
Collaborator:
Hadassah Medical Organization
Information provided by (Responsible Party):
Jonathan D. Huppert, Hebrew University of Jerusalem

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Panic Disorder Behavioral: CBT- both internet and face to face Other: No intervention Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Basic Science
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
Actual Study Start Date : March 24, 2019
Estimated Primary Completion Date : March 24, 2021
Estimated Study Completion Date : March 24, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Panic Disorder

Arm Intervention/treatment
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.
Other: No intervention
Healthy controls will not receive any intervention.

Experimental: panic disorder receiving CBT
40 adult patients diagnosed with primary panic disorder will have their exosomal microRNAs measured 2x over 3 months.
Behavioral: 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.
Other Name: Cognitive behavioral therapy for panic disorder




Primary Outcome Measures :
  1. Differntial expression of plasma exosomal microRNAs [ Time Frame: Pre and post treatment, up to 4 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 3 months, whichever is later, to the maximum of 4 months).


Secondary Outcome Measures :
  1. Change in Panic Disorder Severity Scale (PDSS) [ Time Frame: Weekly during treatment and at pre and post treatment evaluations, up to 4 months apart. ]
    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.

  2. Change in Anxiety Sensitivity Index-3 (ASI-3) [ Time Frame: Weekly during treatment and at pre and post treatment evaluations, up to 4 months apart. ]
    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.

  3. Change in Mobility Inventory [ Time Frame: Weekly during treatment and at pre and post treatment evaluations, up to 4 months apart. ]
    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.

  4. Differntial expression of whole Blood short non-coding RNAs [ Time Frame: Pre and post treatment, up to 4 months apart. ]
    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 4 months).

  5. Change in the Five-Dimensional Curiosity Scale (DCS-5) [ Time Frame: Pre and post treatment, up to 4 months apart. ]
    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 3 months, whichever is later, to the maximum of 4 months).

  6. Changes in Experiences in Close Relationship Scale-Short (ECR-s) [ Time Frame: Pre and post treatment, up to 4 months apart. ]
    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 3 months, whichever is later, to the maximum of 4 months).

  7. Schedule of assessing insight as a predictor and change [ Time Frame: Pre and post treatment, up to 4 months apart. ]
    The scale will be administered by an interviewer as a semistructured interview and will include three items that ask participants, "Do you think you have an illness? Do you think there is something wrong with you?"; "Do you think you have a mental/psychiatric illness?"; and "How do you explain your illness?" The interviewer will rate the items from 0 (no insight) to 2 (good insight). Total score will range from 0 to 6, with higher scores meaning better insight. Will be measured twice: pre and post treatment (post or 3 months, whichever is later, to the maximum of 4 months).

  8. Brown Assessment of Beliefs Scale (predictor and change) [ Time Frame: Pre and post treatment, up to 4 months apart. ]
    This is a semi-structured interview that assesses the degree of insight or delusional beliefs regarding anxiety symptoms. Participants are asked to identify their main fear, which is rated for the following: (a) conviction in beliefs, (b) perception of others' views, (c) explanation of differing views, (d) fixity of beliefs, (e) attempts to disprove beliefs, and (f) insight (recognition of a psychiatric etiology). Each of the 7 items ranges from 0-4, with a total score ranging from 0-28. Higher scores mean poorer insight. Will be measured twice: pre and post treatment (post or 3 months, whichever is later, to the maximum of 4 months).

  9. Changes in Sexual Functioning Questionnaire [ Time Frame: Pre and post treatment, up to 4 months apart. ]
    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 3 months, whichever is later, to the maximum of 4 months).



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04029740


Contacts
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Contact: Shani Vaknine, M.Sc student +972543556299 shani.vaknine@mail.huji.ac.il

Locations
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Israel
Hebrew University of Jerusalem Recruiting
Jerusalem, Israel, 9190501
Contact: Shani Vaknine, M.Sc student    +972543556299    shani.vaknine@mail.huji.ac.il   
Sponsors and Collaborators
Hebrew University of Jerusalem
Hadassah Medical Organization
Investigators
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Principal Investigator: Hermona Soreq, Professor Hebrew University of Jerusalem
Principal Investigator: Ronen Segman, Professor Hadassah Hebrew University Hospital
Principal Investigator: Salomon Israel, Professor Hebrew University of Jerusalem

Publications:
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.

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Responsible Party: Jonathan D. Huppert, Professor, Hebrew University of Jerusalem
ClinicalTrials.gov Identifier: NCT04029740     History of Changes
Other Study ID Numbers: 0577-18-HMO
First Posted: July 23, 2019    Key Record Dates
Last Update Posted: July 23, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All IPD that underlie results in a publication will be placed on a public website after the manuscript is submitted for publication.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data will be available once the manuscript is submitted for publishing.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Disease
Panic Disorder
Pathologic Processes
Anxiety Disorders
Mental Disorders