mango
Senior Member (Voting Rights)
Characterization, Treatment, and Long-term Follow-up of Fatigued Patients in Primary Care (iFAS)
Elin Lindsäter et al, Karolinska Institutet, Stockholm, Sweden
https://clinicaltrials.gov/study/NCT06786832
Study Start (Estimated): 2025-01
Primary Completion (Estimated): 2027-06
Enrollment (Estimated): 500
"Study Overview
Brief Summary
The overarching purpose of this project is to further the understanding of fatigue as a symptom in primary care patients, and to build evidence for a highly accessible treatment targeting fatigue that can be readily implemented in primary care clinics.
Data will be collected within a randomized controlled superiority trial (RCT; N = 500). The primary aim is to evaluate the effectiveness of a novel cognitive behavioral therapy (iFAS: Internet-delivered treatment of Fatigue Across Syndromes) for fatigued patients as compared to care as usual (CAU). Primary outcome will be change in fatigue severity (as measured by the Checklist Individual Strengths, fatigue subscale) pre- to post-treatment (6 months), with long-term controlled follow-up after 12 months. A registry-based follow-up will be conducted up to 60 months post baseline. Moderators and mechanisms of treatment effect will be investigated with the aim to identify potential subgroups of fatigued individuals across and within diagnostic categories that may respond differently to treatment. Lastly, a health economic evaluation of long-term treatment effects will be conducted, which incorporates much needed detailed mapping of care as usual for fatigued patients.
Detailed Description
Fatigue can be defined as extreme and persistent tiredness, weakness, or exhaustion that that could be mental physical, or both. Fatigue is associated with increased healthcare consumption, work disability, and excess mortality, and has been studied extensively under different labels since the 1800's (e.g., neurasthenia, burnout, chronic fatigue syndrome). Studies in primary care populations indicate that about 20-30% of patients report fatigue, with up to 10% of patients presenting with fatigue as their main complaint. Although often considered a disorder-specific characteristic, the etiology and pathogenesis of fatigue are largely unknown and are generally believed to be multifactorial. No biological markers or other objectively measurable factors (such as cognitive impairment) have been found thus far that consistently and sufficiently explain the onset and perpetuation of disorder-specific fatigue. The high prevalence and non-specific nature of fatigue presents a challenge to general practitioners who generally have limited time and resources for assessment and intervention.
Importantly, a potential break-through to how we can understand fatigue has been achieved in recent years, with studies showing that variance in fatigue severity is better explained by transdiagnostic factors (i.e., factors not attributable to a specific medical condition, such as demographic and psychosocial variables and aspects of daily functioning) than by disorder-specific pathophysiology. Further, similar cognitive and behavioral perpetuating mechanisms of fatigue (such as fear avoidance, symptom catastrophizing, self-efficacy, and resting-behavior) have been found across disorders. These findings suggest that a transdiagnostic approach to understanding and treating persistent fatigue might be beneficial for patients and healthcare practitioners, with potentially important implications for treatment.
Treatment of fatigue:
As with other aspects of fatigue, intervention research on fatigue has primarily been conducted in disorder-specific pipelines using disorder-specific protocols. CBT is the most studied treatment, with promising effects for patients with, for example, chronic fatigue syndrome, post-infectious fatigue, and various long-term medical conditions where fatigue is often central (both face-to-face and when delivered via the internet; ICBT). Results from previous RCTs conducted by the investigators have indicated that CBT can be an effective treatment to reduce symptom burden in patients diagnosed with stress-induced exhaustion disorder. Importantly, disorder-specific CBT-protocols for fatigue are largely similar across clinical groups, and the same cognitive and behavioral responses to fatigue have been found to moderate and mediate fatigue severity after CBT across a range of fatigued patient groups.
Even though CBT may hold promise to reduce fatigue severity in different clinical groups, many fatigued patients still do not receive treatment, and not all patients who receive CBT are sufficiently helped. Further research is needed to understand symptom presentation and development as well as treatment moderators, predictors, and mediators of change. Also, there is a significant knowledge gap regarding how fatigue can be identified and treated in an early phase in the primary care context. Given the similarities in effective treatment protocols across fatigued samples, together with potentially common change mechanisms, investigating the effectiveness of a transdiagnostic treatment protocol is a promising avenue with enormous potential utility to increase clinical effects, accessibility, and large-scale implementation. To date, no transdiagnostic treatment specifically targeting fatigue across patient groups has been evaluated.
The current study:
Based on previous disorder-specific treatment protocols aimed to reduce fatigue severity in various fatigued populations, the investigators have developed a transdiagnostic intervention adapted for primary care patients who suffer from persistent fatigue independent of primary diagnosis (iFAS: Internet-delivered treatment of Fatigue Across Syndromes). The treatment is delivered in a blended format (face-to-face therapy combined with internet-delivered texts and exercises) and is administrated over 4 - 6 months. The feasibility of iFAS has recently been evaluated in a non-randomized feasibility trial (Clinical trials ID: NCT06341751).
Study design:
The planned study is a randomized clinical superiority trial that will recruit fatigued patients listed at primary healthcare clinics in Region Stockholm. Study participants (N=500) will be randomized to iFAS (n=250) or to CAU (n=250) by a person not related to the study. Due to the nature of the study, blinding to treatment condition will not be possible. Data collection includes clinician-rated data, self-rated symptom measures, and registry data using interlinked microdata from regional and national registers. Cognitive functioning will be assessed using a digital cognitive test-battery that will be administered at baseline and at the 12-month follow up. Additionally, the study will explore changes in physiological variables from baseline to the 12-month follow-up using continuous data collected from biometric rings.
Elin Lindsäter et al, Karolinska Institutet, Stockholm, Sweden
https://clinicaltrials.gov/study/NCT06786832
Study Start (Estimated): 2025-01
Primary Completion (Estimated): 2027-06
Enrollment (Estimated): 500
"Study Overview
Brief Summary
The overarching purpose of this project is to further the understanding of fatigue as a symptom in primary care patients, and to build evidence for a highly accessible treatment targeting fatigue that can be readily implemented in primary care clinics.
Data will be collected within a randomized controlled superiority trial (RCT; N = 500). The primary aim is to evaluate the effectiveness of a novel cognitive behavioral therapy (iFAS: Internet-delivered treatment of Fatigue Across Syndromes) for fatigued patients as compared to care as usual (CAU). Primary outcome will be change in fatigue severity (as measured by the Checklist Individual Strengths, fatigue subscale) pre- to post-treatment (6 months), with long-term controlled follow-up after 12 months. A registry-based follow-up will be conducted up to 60 months post baseline. Moderators and mechanisms of treatment effect will be investigated with the aim to identify potential subgroups of fatigued individuals across and within diagnostic categories that may respond differently to treatment. Lastly, a health economic evaluation of long-term treatment effects will be conducted, which incorporates much needed detailed mapping of care as usual for fatigued patients.
Detailed Description
Fatigue can be defined as extreme and persistent tiredness, weakness, or exhaustion that that could be mental physical, or both. Fatigue is associated with increased healthcare consumption, work disability, and excess mortality, and has been studied extensively under different labels since the 1800's (e.g., neurasthenia, burnout, chronic fatigue syndrome). Studies in primary care populations indicate that about 20-30% of patients report fatigue, with up to 10% of patients presenting with fatigue as their main complaint. Although often considered a disorder-specific characteristic, the etiology and pathogenesis of fatigue are largely unknown and are generally believed to be multifactorial. No biological markers or other objectively measurable factors (such as cognitive impairment) have been found thus far that consistently and sufficiently explain the onset and perpetuation of disorder-specific fatigue. The high prevalence and non-specific nature of fatigue presents a challenge to general practitioners who generally have limited time and resources for assessment and intervention.
Importantly, a potential break-through to how we can understand fatigue has been achieved in recent years, with studies showing that variance in fatigue severity is better explained by transdiagnostic factors (i.e., factors not attributable to a specific medical condition, such as demographic and psychosocial variables and aspects of daily functioning) than by disorder-specific pathophysiology. Further, similar cognitive and behavioral perpetuating mechanisms of fatigue (such as fear avoidance, symptom catastrophizing, self-efficacy, and resting-behavior) have been found across disorders. These findings suggest that a transdiagnostic approach to understanding and treating persistent fatigue might be beneficial for patients and healthcare practitioners, with potentially important implications for treatment.
Treatment of fatigue:
As with other aspects of fatigue, intervention research on fatigue has primarily been conducted in disorder-specific pipelines using disorder-specific protocols. CBT is the most studied treatment, with promising effects for patients with, for example, chronic fatigue syndrome, post-infectious fatigue, and various long-term medical conditions where fatigue is often central (both face-to-face and when delivered via the internet; ICBT). Results from previous RCTs conducted by the investigators have indicated that CBT can be an effective treatment to reduce symptom burden in patients diagnosed with stress-induced exhaustion disorder. Importantly, disorder-specific CBT-protocols for fatigue are largely similar across clinical groups, and the same cognitive and behavioral responses to fatigue have been found to moderate and mediate fatigue severity after CBT across a range of fatigued patient groups.
Even though CBT may hold promise to reduce fatigue severity in different clinical groups, many fatigued patients still do not receive treatment, and not all patients who receive CBT are sufficiently helped. Further research is needed to understand symptom presentation and development as well as treatment moderators, predictors, and mediators of change. Also, there is a significant knowledge gap regarding how fatigue can be identified and treated in an early phase in the primary care context. Given the similarities in effective treatment protocols across fatigued samples, together with potentially common change mechanisms, investigating the effectiveness of a transdiagnostic treatment protocol is a promising avenue with enormous potential utility to increase clinical effects, accessibility, and large-scale implementation. To date, no transdiagnostic treatment specifically targeting fatigue across patient groups has been evaluated.
The current study:
Based on previous disorder-specific treatment protocols aimed to reduce fatigue severity in various fatigued populations, the investigators have developed a transdiagnostic intervention adapted for primary care patients who suffer from persistent fatigue independent of primary diagnosis (iFAS: Internet-delivered treatment of Fatigue Across Syndromes). The treatment is delivered in a blended format (face-to-face therapy combined with internet-delivered texts and exercises) and is administrated over 4 - 6 months. The feasibility of iFAS has recently been evaluated in a non-randomized feasibility trial (Clinical trials ID: NCT06341751).
Study design:
The planned study is a randomized clinical superiority trial that will recruit fatigued patients listed at primary healthcare clinics in Region Stockholm. Study participants (N=500) will be randomized to iFAS (n=250) or to CAU (n=250) by a person not related to the study. Due to the nature of the study, blinding to treatment condition will not be possible. Data collection includes clinician-rated data, self-rated symptom measures, and registry data using interlinked microdata from regional and national registers. Cognitive functioning will be assessed using a digital cognitive test-battery that will be administered at baseline and at the 12-month follow up. Additionally, the study will explore changes in physiological variables from baseline to the 12-month follow-up using continuous data collected from biometric rings.
