Mental Training for CFS Following EBV Infection in Adolescents

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

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).

Study Overview

• Status: Completed
• Conditions: Fatigue Syndrome, Chronic; Epstein-Barr Virus Infection
• Intervention / Treatment: Behavioral: Mental training

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Akershus
    • Lørenskog, Akershus, Norway, N-1478
      • Dept. of Pediatrics, Akershus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mental training; 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
No Intervention: Routine follow-up; Routine follow-up by the general practitioner, which is normal approach to chronic fatigue following acute EBV infection.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Akershus
• Investigators: Principal Investigator: Vegard Bruun Wyller, PhD, University Hospital, Akershus

Publications and helpful links

General Publications

• Malik S, Asprusten TT, Pedersen M, Mangersnes J, Trondalen G, van Roy B, Skovlund E, Wyller VB. Cognitive-behavioural therapy combined with music therapy for chronic fatigue following Epstein-Barr virus infection in adolescents: a randomised controlled trial. BMJ Paediatr Open. 2020 Oct 21;4(1):e000797. doi: 10.1136/bmjpo-2020-000797. eCollection 2020.
• Malik S, Asprusten TT, Pedersen M, Mangersnes J, Trondalen G, van Roy B, Skovlund E, Wyller VB. Cognitive-behavioural therapy combined with music therapy for chronic fatigue following Epstein-Barr virus infection in adolescents: a feasibility study. BMJ Paediatr Open. 2020 Apr 9;4(1):e000620. doi: 10.1136/bmjpo-2019-000620. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: July 9, 2015
• First Submitted That Met QC Criteria: July 14, 2015
• First Posted (Estimate): July 16, 2015

Study Record Updates

• Last Update Posted (Actual): February 16, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Virus Diseases; Disease Attributes; Disease; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; DNA Virus Infections; Tumor Virus Infections; Herpesviridae Infections; Encephalomyelitis; Syndrome; Fatigue; Infections; Communicable Diseases; Epstein-Barr Virus Infections; Fatigue Syndrome, Chronic
• Other Study ID Numbers: CEBA part 2