Research

The goals of the Research Program linked to the UNSW Fatigue Clinic are to better understand the fatigue conditions (CFS, PCF, PVFS, PIFS), to develop better treatments, and to educate patients and clinicians about the illnesses. 

Previous research:

Over several decades, the Research Program led by Professor Andrew Lloyd and A/Professor Ute Vollmer-Conna, has firstly sought to define the biological basis of fatigue in subjects with post-infective fatigue syndrome (PIFS)1, which is a model of the more heterogeneous clinical disorder, chronic fatigue syndrome (CFS)², and the closely related post-cancer fatigue syndrome (PCF).³ Secondly, whilst awaiting a better understanding of the biological basis of these fatigue conditions, the Research Program has sought to build on the existing evidence of improvements in symptom severity and functional status achieved by cognitive-behavioural therapy (CBT), as well as graded exercise therapy (GET) via an integrated clinical service and research program. 

In early studies in the Dubbo Infection Outcomes Study (DIOS), and more recently the Sydney Infection Outcomes Study (SIOS), subjects with acute infective illnesses were recruited and followed over at least 12 months from the onset of illness. Subjects meeting diagnostic criteria for CFS at 6 months after onset of infection and matched (control) subjects with uncomplicated recovery were then selected to undertake additional intensive research studies examining possible mechanisms underlying the prolonged illness course. These investigations have already established that PIFS is a valid and generalisable model for the onset and evolution of CFS, with a case rate of approximately 10-15% at six months after onset. The studies also demonstrated that severity of the acute illness was the major predictor of PIFS at 3, 6, and 12 months after acute infection, whereas demographic factors (age, gender), and psychological features (personality style, prior depression) were not associated with prolonged illness.

Two of the commonly proposed hypotheses of the biological basis of CFS – abnormal persistence of a viral agent, and an exaggerated, persistent immune response against the virus, were tested in studies in DIOS.^4,5,6 No evidence to support either notion was found. Similarly, in another prospective cohort following women being treated from early stage breast cancer (FolCan), the group has shown a very comparable phenomenon of post-cancer fatigue (PCF),³ and no evidence of immunological disorder underpinning the prolonged illness course.⁷ In SIOS, and also in patients with CFS, the focus has been on the potential role of disturbances in autonomic function (that is the sympathetic and parasympathetic nervous systems) as a correlate of the fatigue conditions. It is clear that autonomic dysfunction is common in patients with medically-unexplained fatigue states,⁸ particularly during sleep and worsens with excessive activity.^9,10

In relation to management of medically unexplained fatigue states, a multi-disciplinary, outpatient treatment program for patients with medically-unexplained fatigue states, has been established in the UNSW Fatigue Clinic. This program provides cognitive behavioural therapy (CBT) and graded exercise therapy (GET) as the main elements. The management program has been designed as independent treatment modules that are combined by the clinicians (exercise physiologists and clinical psychologists) to form an integrated treatment approach, including four core modules: activity pacing and graded exercise therapy; education; interventions for sleep-wake cycle disturbance; and interventions for neurocognitive disturbance. Additionally, there are three optional modules targeting: depression, anxiety, and coping. This integrated CBT / GET intervention has been shown to be both safe and effective in relieving symptoms and improving functional capacity in medically-unexplained fatigue states including CFS, PCF, PVFS, and PIFS.^11,12

The ongoing research projects seeking to improve treatment for patients with medically-unexplained fatigue states include: a study of the potential benefits of the addition of the brain stimulant medication, modafinil, in relieving the characteristic post-exertional exacerbation of symptoms after exercise (see Theme 4 below); investigations of the association between fatigue and pain during the development and after the establishment, of a chronic fatigue state (see Theme 4 below); having found autonomic dysfunction to be common in patients with medically-unexplained fatigue states,¹³ an investigation of individualized relaxation training to increase parasympathetic activity and potentially improve symptoms is being undertaken); with established evidence for the overall effectiveness of the CBT / GET intervention, and yet very few services offering such treatment nationally, an online education and training program for clinicians to acquire the skills in delivery of CBT / GET for patients with medically-unexplained fatigue has been developed and is now being evaluated (see Theme 3 below); finally, as neurocognitive disturbance (concentration and memory difficulties, sometimes referred to as ‘brain fog’) is sometimes the major function-limiting symptom in patients with medically unexplained fatigue states, a structured brain-training program (analogous to GET) has been developed and piloted,¹⁴ and similarly found to be effective in a larger replication study¹⁵.

Latest update:

The UNSW Fatigue Clinic and Research Program has been awarded a 2022 CommBank Staff Foundation Community Grant. 

The 2022 program saw CommBank employees nominate organisations they were passionate about to receive a grant.  A total of $2m has been awarded via $10,000 grants to a broad range of community organizations across Australia. This will assist the UNSW Fatigue Clinic and Research Program to continue the important work we are doing developing online educational resources for patients and clinicians about the illness, its diagnosis and management.