Clinical trial NCT02592564: Brain Plasticity and Cellular Aging After Internet-delivered CBT for Social Anxiety Disorder
Official title: The Brain´s Plasticity and Change in Cellular Aging After Internet-delivered Cognitive Behavior Therapy for Social Anxiety Disorder
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Anxiety Disorders
Social Anxiety Disorder
Keywords: Magnetic Resonance Imaging
Cognitive Behavior Therapy
Telomerase
Telomere Length, Mean Leukocyte
Lead sponsor: Linkoeping University
Sponsor class: OTHER_GOV
Collaborators: name: Umeå University
name: Uppsala University
name: Stockholm University
name: Karolinska Institutet
First posted: 2015-10-30
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study evaluates underlying psychological and biological mediators in Internet-delivered cognitive behavior therapy for adults with social anxiety disorder.

Detailed description: Internet-delivered cognitive behavior therapy for social anxiety disorder has previously demonstrated to target and affect the brain´s fear network, typically neural response in the amygdala ameliorate after effective psychological treatment. Commonly, neuroimaging studies have performed brain imaging at pre- and post-intervention, yet, longitudinal study designs including several repeated measures of neural response over the course of treatment are currently missing in anxiety disorder. In the current study the participants will undergo magnetic resonance imaging (MRI) at four occasion. a) Twice before treatment initiation (9 weeks apart), b) at week 4 (during treatment), c) and directly after treatment termination.

Biological aging can be quantified at the individual cell level by measuring telomere length in peripheral immune cells (leukocytes). Telomeres are located at the end of each chromosome and protect the genetic material during cell division. Telomerase is an enzyme that can lengthen telomeres, and have in this way a protective function against accelerated cellular aging. Variations in these bodily processes have been associated with psychiatric manifestations such as anxiety and depression. In the current study the participant´s telomere length and telomerase activity will be assessed at three occasion. a) Twice before treatment initiation (9 weeks apart), and b) directly after treatment termination.

Eligibility criteria: Inclusion Criteria:

* Social Anxiety Disorder as primary diagnosis (DSM-5)
* Otherwise somatically healthy
* Willingness to participate in a symptom provocation brain imaging trial

Exclusion Criteria:

* Concurrent psychological treatment
* Treatment of social anxiety within the three months preceding the study
* Chronic use of prescribed medication that could influence the results (anxiolytic or antidepressant drugs, certain hypnotics or herbs like St Johns Wort)
* Contraindications for MRI investigation (implants or other metal objects in the body, brain and heart operations)
* Pregnancy or planned pregnancy during the first 6 months of the study period
* Postmenopausal women
* Any neurological disorders
* Depressive symptoms, as determined by scoring more than 20 on the MADRS questionnaire (self-report version)
* Suicidal ideation (scoring more than 2) on the self-report version of MADRS, item 9
* Suicide at moderate risk (MINI v7)
* Bipolar disorder (MINI v7)
* Psychotic syndromes (MINI v7)
* Substance abuse disorders (MINI v7)
* Alcohol abuse (MINI v7)
* Any eating disorder (MINI v7)
* Antisocial personality disorder (MINI v7)

Primary outcomes:
measure: Clinically Global Impression-Improvement scale (CGI-I; Change from baseline)
timeFrame: At week 20 (post-treatment), and at 6, 12, and 60 months
measure: Liebowitz Social Anxiety Scale, Self-report version (LSAS-SR; Change from baseline)
timeFrame: Screening, Baseline 1 (week 0), Baseline 2 (week 9), weekly during treatment (week 10-19), week 20 (post-treatment), and at 6, 12, and 60 months
Secondary outcomes:
measure: Clinically Global Impression-Severity scale (CGI-S)
timeFrame: Screening, week 20 (post-treatment), and at 6, 12, and 60 months
measure: Social Phobia Screening Questionnaire (SPSQ)
timeFrame: Screening, week 20 (post-treatment), and at 6, 12, and 60 months
measure: Beck Anxiety Inventory (BAI)
timeFrame: Screening, week 20 (post-treatment), and at 6, 12, and 60 months
measure: Social Interaction Anxiety Scale (SIAS)
timeFrame: Screening, week 20 (post-treatment), and at 6, 12, and 60 months
measure: Social Phobia Scale (SPS)
timeFrame: Screening, week 20 (post-treatment), and at 6, 12, and 60 months
measure: Montgomery Åsberg Depression Rating Scale, Self-report version (MADRS-S)
timeFrame: Screening, Baseline 1 (week 0), Baseline 2 (week 9), week 13 during treatment, week 20 (post-treatment), and at 6, 12, and 60 months
measure: Subjective unit of discomfort on fear and distress (SUD)
timeFrame: Before experimental tasks while undergoing MRI, at Baseline 1 (week 0), Baseline 2 (week 9), week 13 during treatment, week 20 (post-treatment)
measure: Social Probability/Cost Questionnaire
timeFrame: Baseline 1 (week 0), Baseline 2 (week 9), week 13 during treatment, week 20 (post-treatment), and at 6, 12, and 60 months
measure: Quality of Life (QOLI)
timeFrame: Screening, week 20 (post-treatment), and at 6, 12, and 60 months
measure: Social Network Index (SNI)
timeFrame: Baseline 1 (week 0)
measure: Brown Attention-Deficit Disorder Scales (Brown ADD)
timeFrame: Baseline 1 (week 0)
measure: Difficulties in Emotion Regulation Scale (DERS)
timeFrame: Baseline 1 (week 0), Baseline 2 (week 9), week 13 during treatment, week 20 (post-treatment), and at 6, 12, and 60 months
measure: Treatment Credibility Scale (TCS)
timeFrame: Baseline 2 (week 9), week 13 during treatment
measure: Revised NEO Personality Inventory (NEO-PI-R)
timeFrame: Baseline 1 (week 0)
measure: Insomnia Severity Index (ISI)
timeFrame: Baseline 1 (week 0)
measure: Karolinska Sleep Questionnaire (KSQ)
timeFrame: Baseline 1 (week 0)
measure: State-Trait Anxiety Inventory (STAI-T)
timeFrame: Baseline 1 (week 0)
measure: State-Trait Anxiety Inventory (STAI-S)
timeFrame: Baseline 1 (week 0), Baseline 2 (week 9), week 13 during treatment, week 20 (post-treatment)
measure: MINI International Neuropsychiatric Interview
timeFrame: Screening
Other outcomes:
measure: Resting-state fMRI 6 minutes
timeFrame: Baseline 1 (week 0), Baseline 2 (week 9), week 13 during treatment, week 20 (post-treatment)
measure: Self-referential criticism
timeFrame: Baseline 1 (week 0), Baseline 2 (week 9), week 13 during treatment, week 20 (post-treatment)
measure: Hariri´s Hammer (emotional face perception)
timeFrame: Baseline 1 (week 0), Baseline 2 (week 9), week 13 during treatment, week 20 (post-treatment)
measure: Brain habituation during face perception
timeFrame: Baseline 1 (week 0), Baseline 2 (week 9), week 13 during treatment, week 20 (post-treatment)
measure: Diffusion Tensor Imaging (DTI)
timeFrame: Baseline 1 (week 0), Baseline 2 (week 9), week 13 during treatment, week 20 (post-treatment)
measure: Leukocyte telomere length
timeFrame: Baseline 1 (week 0), Baseline 2 (week 9), week 20 (post-treatment)
measure: Telomere terminal transferase (telomerase)
timeFrame: Baseline 1 (week 0), Baseline 2 (week 9), week 20 (post-treatment)
Locations:
city: Umeå
country: Sweden
facility: Umeå university
Study officials:
affiliation: Stockholm University, Karolinska Institutet
name: Kristoffer NT Månsson, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mansson KN, Carlbring P, Frick A, Engman J, Olsson CJ, Bodlund O, Furmark T, Andersson G. Altered neural correlates of affective processing after internet-delivered cognitive behavior therapy for social anxiety disorder. Psychiatry Res. 2013 Dec 30;214(3):229-37. doi: 10.1016/j.pscychresns.2013.08.012. Epub 2013 Sep 21.
citation: Mansson KN, Frick A, Boraxbekk CJ, Marquand AF, Williams SC, Carlbring P, Andersson G, Furmark T. Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning. Transl Psychiatry. 2015 Mar 17;5(3):e530. doi: 10.1038/tp.2015.22.
citation: Lindqvist D, Epel ES, Mellon SH, Penninx BW, Revesz D, Verhoeven JE, Reus VI, Lin J, Mahan L, Hough CM, Rosser R, Bersani FS, Blackburn EH, Wolkowitz OM. Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging. Neurosci Biobehav Rev. 2015 Aug;55:333-64. doi: 10.1016/j.neubiorev.2015.05.007. Epub 2015 May 18.
citation: Furmark T, Tillfors M, Marteinsdottir I, Fischer H, Pissiota A, Langstrom B, Fredrikson M. Common changes in cerebral blood flow in patients with social phobia treated with citalopram or cognitive-behavioral therapy. Arch Gen Psychiatry. 2002 May;59(5):425-33. doi: 10.1001/archpsyc.59.5.425.