Mental Training for CFS Following EBV Infection in Adolescents

Study Overview
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Brief Summary
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The general aim of this study is to investigate the effect of an individually tailored mental training program in adolescents developing chronic fatigue syndrome (CFS) after an acute Epstein Barr-virus (EBV) infection. Endpoints include physical activity (primary endpoint), symptoms (fatigue, pain, insomnia), cognitive function (executive functions) and markers of disease mechanisms (autonomic, endocrine, and immune responses).

Detailed Description
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EBV-infection is a well-known trigger of CFS. A closely related research project (Chronic fatigue following acute Epstein-Barr virus infection in Adolescents; ClinicalTrials ID:NCT02335437) is a combined prospective and cross-sectional study of 200 adolescents suffering from acute EBV infection. The primary aim of that study is to identify factors that predispose to CFS 6 months after the acute infection. Thus, that project will provide a sample of thoroughly characterized CFS patients, all having the same precipitation factor (EBV-infection). The present project is an intervention trial in the subgroup of patients that actually did develop CFS 6 months after the acute EBV infection. Patients will be randomised 1:1 to either a mental training program (10 sessions) combining elements from cognitive behavioral therapy and music therapy, or routine follow-up from the general practitioner. By its nature, treatment group allocation cannot be blinded; however, both patients and therapists will be blinded for end-point evaluation. An extensive investigational program will be carried out at three time points: Prior to the intervention, immediately after the intervention, and 1 year after the intervention. The program includes: Clinical examination; Pain threshold assessment; Cardiovascular assessment; Cognitive assessment; Sampling of biological material (blood and urine); Questionnaire; Brain fMRI; Qualitative interview; Monitoring of physical activity (accelerometer)

Official Title
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Mental Training for Chronic Fatigue Syndrome (CFS/ME) Following EBV Infection in Adolescents: A Randomised Controlled Trial

Conditions
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Fatigue Syndrome, Chronic, Epstein-Barr Virus Infection

Intervention / Treatment
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* Behavioral: Mental training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant in the research project CEBA (Chronic fatigue following acute Epstein-Barr virus infection in adolescents, NCT02335437) Chronic fatigue at 6 months (a sum score of dichotomized responses ≥ 4 on the Chalder Fatigue questionnaire) Exclusion Criteria: Other illnesses that might explain the fatigue Bedridden

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mental training<br>The intervention consists of one introductory session (patients and their parents/next-of-kin), followed by 9 individual therapy sessions (one each week) of 1.5 hours duration and related home-work, combining elements from cognitive behavioural therapy and music therapy: Important elements of the mental training program are: Psychoeducation: Theories of CFS/ME pathophysiology and treatment rationale Relaxation: Bodily stress reduction, mindfulness Visualization: Contact with positive emotions, techniques of worrying reduction Experiences: Behavioral 'experiments' (individually adjusted), 'trick into action' Cognitive challenges: Challenging thoughts about disease process, stimulus and outcome expectancies, prognosis | Behavioral: Mental training<br> <br> |
| No Intervention: Routine follow-up<br>Routine follow-up by the general practitioner, which is normal approach to chronic fatigue following acute EBV infection. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical activity | Mean steps/day during 7 consecutive days measured by accelerometer | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma catecholamines |  | 12 weeks | 
| Plasma catecholamines |  | 64 weeks | 
| Urine cortisol:creatinin ratio |  | 12 weeks | 
| Urine cortisol:creatinin ratio |  | 64 weeks | 
| Degree centrality index of cytokine network | An index of node centrality, based upon network analyses | 12 weeks | 
| Degree centrality index of cytokine network | An index of node centrality, based upon network analyses | 64 weeks | 
| Number of NK-cells |  | 12 weeks | 
| Number of NK-cells |  | 64 weeks | 
| Supine heart rate |  | 12 weeks | 
| Supine heart rate |  | 64 weeks | 
| Heart rate variability indices |  | 12 weeks | 
| Heart rate variability indices |  | 64 weeks | 
| Heart rate, blood pressure and total peripheral resistence responses to upright posture |  | 12 weeks | 
| Heart rate, blood pressure and total peripheral resistence responses to upright posture |  | 64 weeks | 
| Working memory | Digit span forward and backward test | 12 weeks | 
| Working memory | Digit span forward and backward test | 64 weeks | 
| Cognitive inhibition | Color-word interference test from the D-KEFS instrument | 12 weeks | 
| Cognitive inhibition | Color-word interference test from the D-KEFS instrument | 64 weeks | 
| Correlation matrix indices of regions of interests (ROIs) in the brain salience network | Functional connectivity analyses from resting state brain fMRI | 12 weeks | 
| Correlation matrix indices of regions of interests (ROIs) in the brain salience network | Functional connectivity analyses from resting state brain fMRI | 64 weeks | 
| Fatigue score (Chalder fatigue questionnaire) |  | 12 weeks | 
| Fatigue score (Chalder fatigue questionnaire) |  | 64 weeks | 
| Pain scores (Brief pain Inventory) |  | 12 weeks | 
| Pain scores (Brief pain Inventory) |  | 64 weeks | 
| Quality of Life score (PedsQL) |  | 12 weeks | 
| Quality of Life score (PedsQL) |  | 64 weeks | 
| Anxiety and depression score (HADS) |  | 12 weeks | 
| Anxiety and depression score (HADS) |  | 64 weeks | 
| Alexithymia score (TAS-20) |  | 12 weeks | 
| Alexithymia score (TAS-20) |  | 64 weeks | 
| Insomnia score (KSQ) |  | 12 weeks | 
| Insomnia score (KSQ) |  | 64 weeks | 
| Pain threshold (algometry) |  | 12 weeks | 
| Pain threshold (algometry) |  | 64 weeks | 
| Disability score (FDI) |  | 12 weeks | 
| Disability score (FDI) |  | 64 weeks | 
| Side effect and unexpected events questionnaire |  | 3 weeks | 
| Side effect and unexpected events questionnaire |  | 6 weeks | 
| Side effect and unexpected events questionnaire |  | 9 weeks | 
| Side effect and unexpected events questionnaire |  | 12 weeks | 
| Physical activity | Mean steps/day during 7 consecutive days measured by accelerometer | 64 weeks |