Postcancer Fatigue Clinical Trial
Official title:
An Explorative Study on Physiological and Neurophysiological Determinants of Fatigue in Cancer Survivors
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=57), 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=21). 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.
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT01651754 -
Humoral and Cellular Immune Responses After Influenza Vaccination in Patients With Postcancer Fatigue and in Patients With Chronic Fatigue Syndrome
|
N/A |