Reducing severe fatigue in patients with diffuse glioma: a study protocol for an RCT on the effect of blended cognitive behavioural therapy

Abstract

Background Fatigue is the most frequent and burdensome symptom of patients with diffuse glioma. It is closely linked to decreased health-related quality of life and symptoms such as depression and sleep disturbances. Currently, there is no evidence-based treatment that targets severe fatigue in patients with brain tumours. Cognitive behavioural therapy is aimed at fatigue-maintaining beliefs and behaviour. This therapy has been proven effective in reducing severe fatigue in cancer survivors and patients with multiple sclerosis. A blended therapy program combines sessions with a therapist with therapist-guided web-based therapy modules. The aim of this randomized controlled trial is to determine the efficacy of blended cognitive behavioural therapy in treating severe fatigue in patients with diffuse glioma. Methods We will include a maximum of 100 patients with diffuse glioma with clinically and radiologically stable disease and severe fatigue (i.e. Checklist Individual Strength, subscale fatigue severity ≥ 35). Patients will be randomized to blended cognitive behavioural therapy or a waiting list condition. The 12-week intervention GRIP on fatigue consists of five patient-therapist sessions and five to eight individualized web-based therapy modules supported by email contact. The primary outcome measure is fatigue severity. Secondary outcome measures include sleep quality, health-related quality of life, depression, anxiety, functional impairment and subjective and objective cognitive functioning. Primary and secondary outcome measures will be assessed at baseline and after 14 and 24 weeks. Magnetoencephalography and MRI will be used to evaluate potential biomarkers for intervention success. This trial has a Bayesian design: we will conduct multiple interim analyses to test for efficacy or futility of the trial. This is the first trial within the GRIP trial platform: a platform developing four to five different interventions for the most common symptoms in patients with diffuse glioma. Discussion The results of the GRIP on fatigue trial will provide information about the efficacy of this intervention on fatigue in patients with diffuse glioma. Multiple other outcomes and possible predictors of treatment success will also be explored. Trial registration Netherlands Trial Register NL8711. Registered on 14 June 2020.

Non-pharmacological fatigue interventions for patients with a primary brain tumour: a scoping review protocol

“…In this review, samples of adult patients with PBTs of grade 2–4 will be included. This is supported by previous research by Röttgering 3 , finding that there was not a significant difference in fatigue severity reported by individuals with different tumour grades ranging from 2 to 4. 3 …”

“…Fatigue is the most prevalent symptom for patients with PBT 3. Fatigue associated with having cancer and consequent treatments such as radiotherapy and chemotherapy is known as cancer-related fatigue (CRF) 4.…”

“…2 Fatigue is the most prevalent symptom for patients with PBT. 3 Fatigue associated with having cancer and consequent treatments such as radiotherapy and chemotherapy is known as cancer-related fatigue (CRF). 4 The National Comprehensive Cancer Network defines CRF as 'a distressing, persistent, subjective sense of physical, emotional, and/ or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning'.…”

Toward unraveling the correlates of fatigue in glioma

“…There are several effective interventions targeting fatigue in cancer patients, including cognitive behavioral therapy, mindfulness, exercise, activity enhancement, problem-solving therapy, and acceptance and commitment therapy 26,48 . Those interventions might also be promising in treating fatigue in patients with glioma [48][49][50] .…”

“…26,46 Those interventions might also be promising in treating fatigue in patients with glioma. [46][47][48] Unfortunately, we did not assess whether antiepileptic drugs (AEDs) were associated with fatigue, since some studies do suggest that AEDs could result in fatigue. 5,10,49 Therefore it might be worthwhile to investigate whether switching between AEDs or lowering the dosage would be a useful approach to ameliorate fatigue.…”