An Explorative Study on Physiological and Neurophysiological Determinants of Fatigue in Cancer Survivors

2014-08-27 03:14:52 | BioPortfolio


Postcancer fatigue is a severe and invalidating problem, impairing quality of life. About 20 to 40% of the patients remain fatigued, at least one year after successful cancer treatment. Fortunately, there is an effective treatment for postcancer fatigue; cognitive behavior therapy. However, no cause for postcancer fatigue has been identified yet. The aim of the study is to identify factors that (partly) cause postcancer fatigue to improve the theoretical understanding of fatigue and to improve the diagnostics of fatigue, predict therapy outcome, and facilitate other treatment options.

In this study, disease-free fatigued cancer patients, who finished treatment for cancer at least one year and maximally ten years ago, will be approached for this study. They will be compared to non-fatigued patients.

First, a baseline assessment will take place. Magnetic resonance imaging of the brains will be performed to assess brain volume and magnetic resonance spectroscopy will be performed to measure the concentrations of specific substances in the brains. Changes in the volume of parts of the brains have been observed in (non-cancer) patients with the chronic fatigue syndrome (CFS), in comparison with healthy controls. In addition, abnormal concentrations of specific substances have been observed in patients with CFS compared to healthy controls. To assess muscle fatigue, a two-minute endurance test of the upper arm will be administered at maximal voluntary contraction. Next to differences in the brains, CFS patients showed (central) muscle fatigue. A maximal exercise test on a bicycle will be performed to assess physical fitness. Physical activity in fatigued cancer survivors is decreased, compared to healthy controls. It is not known whether physical deconditioning originated during the cancer treatment is the reason why these patients are still less active. In addition, patients and controls will wear an actometer for two weeks to register baseline daily physical activity and for an additional 5 days after the maximal exercise test, to assess the effect of exercise on the daily physical activity. Finally, patients and controls will complete standardized questionnaires and will perform neurological/psychological tests, like a reaction time test and a short time memory task, at baseline.

The results of the non-fatigued and the fatigued patients will be compared at baseline. For the non-fatigued participants, the study will be finished after the baseline measurements. The fatigued participants will start with cognitive behavior therapy immediately after the baseline measurements or after 6 months, depending on the randomization.

At the end of the therapy, after six months, or after 6 months of waiting for cognitive behavior therapy, a second assessment will take place, comparable to the baseline measurements. These results will be compared with the baseline situation to analyze the effect of cognitive behavior therapy on the (possible) causes of postcancer fatigue.


Fatigue after curative treatment for cancer is a severe and invalidating problem. 20-40% of disease-free cancer patients mention fatigue as a frequent complaint, impairing quality of life. In search for (neuro)physiological factors determining fatigue, our centre has recently demonstrated the presence of morphological differences in the brains of non-cancer patients with the chronic fatigue syndrome (CFS) compared with healthy volunteers. Both in patients with CFS and in fatigued patients with neuromuscular diseases we showed that fatigue has a central neurophysiological component (so-called central activation failure). Others have shown that chronic fatigue is associated with altered brain metabolism. Studies with proton MR spectroscopy (1H MRS) have demonstrated a higher choline to creatine ratio in the brains of chronically fatigued patients. This suggests increased cell membrane turnover. Also reduced levels of N-acetylaspartate-creatine ratio (NAA/Cr) in the right hippocampus have been observed in these patients, which suggests a decrease in functional axons. Finally, elevated ventricular lactate was observed, which suggests changes in brain glucose metabolism. Actigraphy has shown that actual physical activity in fatigued cancer survivors is decreased compared to healthy controls. It is not known whether physical deconditioning originated during the actual cancer treatment is the reason why these patients are still less active. Until now no other (neuro)physiological factors have been identified explaining fatigue in cancer survivors. Recently we have shown that Cognitive Behaviour Therapy (CBT) especially designed for fatigued cancer patients is an effective treatment.

Aim: To identify and measure (neuro)physiological factors of fatigue in fatigued cancer survivors and to determine the role of these factors in the maintaining of fatigue. The identification of (neuro)physiological factors of persistent fatigue can help to improve the diagnostics of fatigue, predict therapy outcome and facilitate other treatment options. Finally, if (neuro)physiological characteristics of fatigue can be influenced by CBT it will enhance our understanding of the mechanism causing fatigue.

Research questions: 1) What are characteristic (neuro)physiological factors of fatigue in disease-free cancer patients? 2) To which degree can these factors be influenced by Cognitive Behaviour Therapy?

Design: In this explorative study fatigued disease-free cancer patients (n=80), who finished treatment for cancer at least one year and maximally ten years ago, will be approached for this study and asked for informed consent. They will be compared to age and sex matched non-fatigued patients (n=52). First, a base-line assessment will take place, which includes magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to assess brain morphology and brain metabolites, respectively. To assess peripheral and central fatigue a two-minute endurance test will be administered at maximal voluntary (isometric) contraction (MVC). During the test changes in EMG and force indicate peripheral fatigue, while central fatigue is studied by the twitch interpolation technique. A maximal exercise test will be performed to assess physical fitness and deconditioning. At baseline patients will also be given an actometer which will register daily activity during two weeks. Further, the actometer will register daily activity up to five days after the maximal exercise test. Finally, at baseline patients will fill out a standardized questionnaire, including the Checklist Individual Strength and a self-observation list to assess fatigue severity. Then, the fatigued patients start immediately with Cognitive Behaviour Therapy (CBT). At the end of the therapy, after 6 months, a second assessment will take place in this group of patients. The assessment consists of the same measurements as at baseline. The results will be compared with the baseline situation to analyze the effect of CBT on the (neuro)physiological parameters.

Relevance of this study: Fatigue long after treatment for cancer is a frequently occurring problem, which has important consequences for quality of life in these patients. Identification of characteristic (neuro)physiological factors of fatigue in disease-free cancer patients may not only serve a theoretical understanding of this invalidating condition, but may also provide an objective biological marker that could support the diagnosis and follow-up of treatment. The identification of (neuro)physiological factors which play a role in fatigue after cancer may aid in the early recognition of patients who are at risk for developing fatigue and may lead to early intervention and/or different treatment strategies.

Study Design

Allocation: Randomized, Control: Active Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Postcancer Fatigue


immediate CBT, Delayed CBT


University Medical Centre Nijmegen
6500 HB


Not yet recruiting


Radboud University

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:14:52-0400

Clinical Trials [604 Associated Clinical Trials listed on BioPortfolio]

Cause and Consequence of Neural Fatigue

While the scientific community understands quite well why muscles ache after prolonged exercise, the origins of mental fatigue remain totally mysterious. Existing theories remain at a psyc...

Cancer Related Fatigue in Patients Receiving Chemotherapy

The purpose of this study is to examine the degree of fatigue in patients receiving chemotherapy. Special interest goes out to the course of fatigue throughout five treatments and the acti...

Validation of the French Version of the Fatigue Score "Brief Fatigue Inventory ( BFI)".

Fatigue, or asthenia, is an important symptom for the diagnosis and follow-up of patients in routine as well as research oriented clinical practice. Various questionnaires measuring fatig...

Fatigue Intervention Co-design Study in Teenagers and Young Adults With Cancer

Fatigue is one of the most common and distressing symptoms in teenage and young adult cancer patients. Despite this, there has been virtually no research evaluating treatment for cancer-re...

Delayed-immediate Versus Delayed Breast Reconstruction in Breast Cancer Patients With Mastectomy and Radiation Therapy

In breast cancer patients treated by mastectomy and adjuvant post-mastectomy radiation therapy (PMRT) reconstruction is often delayed until 6 - 12 month after completion of chemotherapy an...

PubMed Articles [2095 Associated PubMed Articles listed on BioPortfolio]

The impairing effects of mental fatigue on response inhibition: An ERP study.

Mental fatigue is one of the main reasons for the decline of response inhibition. This study aimed to explore the impairing influence of mental fatigue on a driver's response inhibition. The effects o...

Fatigue after breast cancer treatment: Biobehavioral predictors of fatigue trajectories.

Fatigue is a common side effect of cancer treatment, but there is considerable variability in fatigue severity and persistence among survivors. This study aimed to characterize longitudinal trajectori...

Sasa quelpaertensis leaf extract mitigates fatigue and regulates the transcriptome profile in mice.

It has been reported that various plant species may enhance the elimination of fatigue-related metabolites. However, relatively few studies have directly addressed the potential anti-fatigue effects.

WITHDRAWN: Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome.

Chronic fatigue is increasingly common. Conventional medical care is limited in treating chronic fatigue, leading some patients to use traditional Chinese medicine therapies, including herbal medicine...

Validation of the Amharic Version of the Brief Fatigue Inventory (BFI-Am) for Assessment of Cancer Related Fatigue in Ethiopian Cancer Patients.

Even though cancer related fatigue (CRF) is a highly prevalent and distressing symptom associated with cancer and its treatment; it is mostly under-screened, under-assessed and under-treated. The Brie...

Medical and Biotech [MESH] Definitions

A state arrived at through prolonged and strong contraction of a muscle. Studies in athletes during prolonged submaximal exercise have shown that muscle fatigue increases in almost direct proportion to the rate of muscle glycogen depletion. Muscle fatigue in short-term maximal exercise is associated with oxygen lack and an increased level of blood and muscle lactic acid, and an accompanying increase in hydrogen-ion concentration in the exercised muscle.

The lack of development of SEXUAL MATURATION in boys and girls at a chronological age that is 2.5 standard deviations above the mean age at onset of PUBERTY in a population. Delayed puberty can be classified by defects in the hypothalamic LHRH pulse generator, the PITUITARY GLAND, or the GONADS. These patients will undergo spontaneous but delayed puberty whereas patients with SEXUAL INFANTILISM will not.

A common nonarticular rheumatic syndrome characterized by myalgia and multiple points of focal muscle tenderness to palpation (trigger points). Muscle pain is typically aggravated by inactivity or exposure to cold. This condition is often associated with general symptoms, such as sleep disturbances, fatigue, stiffness, HEADACHES, and occasionally DEPRESSION. There is significant overlap between fibromyalgia and the chronic fatigue syndrome (FATIGUE SYNDROME, CHRONIC). Fibromyalgia may arise as a primary or secondary disease process. It is most frequent in females aged 20 to 50 years. (From Adams et al., Principles of Neurology, 6th ed, p1494-95)

A delayed rectifier subtype of shaker potassium channels that conducts a delayed rectifier current. It contributes to ACTION POTENTIAL repolarization of MYOCYTES in HEART ATRIA.

A group of slow opening and closing voltage-gated potassium channels. Because of their delayed activation kinetics they play an important role in controlling ACTION POTENTIAL duration.

More From BioPortfolio on "An Explorative Study on Physiological and Neurophysiological Determinants of Fatigue in Cancer Survivors"

Quick Search


Relevant Topics

  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...

Head and neck cancers
Cancer can occur in any of the tissues or organs in the head and neck. There are over 30 different places that cancer can develop in the head and neck area. Mouth cancers (oral cancers)  - Mouth cancer can develop on the lip, the tongue, the floor...

Searches Linking to this Trial