THE EFFICACY OF COGNITIVE BEHAVIOURAL INTERNET THERAPY FOR ADULT PATIENTS WITH CHRONIC FATIGUE SYNDROME: A RANDOMISED CONTROLLED TRIAL.

Chronic fatigue syndrome (CFS) is characterized by severe fatigue that lasts
longer than 6 months and leads to functional impairments. It is not the result
of an organic disease or ongoing exertion and is not alleviated by rest [1].
Besides severe fatigue and substantial functional impairments, most patients
report additional symptoms. According to the CFS criteria of the U.S. Centers
for Disease Control [1] a patient must report four out of eight additional
symptoms: unrefreshing sleep, postexertional malaise, headache, muscle pain,
multi-joint pain, sore throat, tender lymph nodes, and concentration and memory
impairment. Only in the Netherlands there are at least 30.000-40.000 CFS
patients according to Dutch Health Council. The natural course of CFS without
treatment is unfavourable; only 5% of the patients recover spontaneously [2].

Cognitive behavioural therapy (CBT) for CFS is an effective [3, 4] but
intensive treatment. CBT for CFS is directed at changing fatigue-related
cognitions and behaviours that perpetuate the fatigue and disabilities. A
substantial subgroup of patients fully recover during treatment [3]. It
requires an average of 14 face to face sessions to change the fatigue
perpetuating factors [5]. Wider implementation of this effective therapy is
hampered by the fact that the treatment is time consuming for both patient and
therapist. Moreover, licensed cognitive behaviour therapists need additional
training and supervision to learn to treat CFS. The aforementioned leads to a
limited treatment capacity is limited and makes that many CFS patients do not
get the treatment they need.

Therefore, less intensive interventions are needed to reach more patients with
a limited number of qualified therapists. There is evidence that not all
patients need an intensive treatment. A previous study of our own research
group showed in a randomized controlled trial (RCT) for a subgroup of patients
with CFS a less intensive treatment sufficed to significantly reduce fatigue
and disabilities [6]. We developed a minimal intervention based on CBT that
consisted of a booklet with self-instructions and two-weekly email contact
with a trained therapist.

Although the minimal intervention significantly reduced fatigue it was only
effective in a limited number of patients (about 25%). Recent research in
adolescents CFS patients has shown that treatment delivered by the internet can
be highly effective and comparable in effectiveness to face to face therapy. In
the present study we want to test the efficacy of an internet based
intervention for adult CFS patients. It is developed on the basis of the
self-help booklet and consist of structured exercises with feedback provided by
the therapist. It is unclear how much feedback from the therapist is needed to
for patients to profit from an internet based intervention. To test this we
developed two versions of the CBIT: one in which the patients will receive
frequent feedback according to a predefined schedule (protocol driven feedback)
and one version in which patients only receive support on demand (support on
demand).

In the first phase of this study we will investigate the efficacy of CBIT for
adult CFS patients with different levels of support offered by therapists. Both
conditions will be compared to a waiting list control group and with each other
with respect to its effect on fatigue severity (primary outcome measure).

We expect that not all patients will profit from the CBIT and therefore we
added a second phase to the study. In this second phase patients who have not
sufficiently benefited from the CBIT (i.e. are still severely fatigue and/or
disabled at post-intervention assessment) will be offered regular face to face
cognitive behaviour therapy. This stepped care (CBITfollowed by regular CBT if
the patient is still fatigued) will be compared to care as usual (CBT after a
waiting period) in a randomised non-inferiority trial.

The main research question of this study is:
1. Does CBITlead to a reduction of fatigue severity in adult patients with CFS
compared to a waiting list condition?

Secondary research questions for phase one of the study:
2. Does CBIT lead to a reduction of disabilities, psychological distress and/or
a progress of clinical significant improvement of fatigue and/or quality
adjusted life years in adult patients with CFS compared to a waiting list
condition?

3. Is CBIT with protocol driven feedback more effective than CBITwith support
on demand concerning its effect on fatigue severity?

Secondary research questions of phase two of the study:
4. Is stepped care consisting of CBIT with protocol driven feedback or with
support on demand followed by regular face to face therapy (for those patients
who are still fatigued and/ or disabled after cognitive behavioural internet
therapy) non-inferior to care as usual i.e. CBT following the waiting list with
respect to its effect on fatigue severity?

5. Is stepped care consisting of CBIT followed by regular face to face therapy
(for those patients who are still fatigued and/ or disabled after cognitive
behavioural internet therapy) as effective as care as usual i.e. CBT following
the waiting list with respect to its effect on level of disabilities and
clinical significant improvement of fatigue?

6. Is stepped care consisting of CBIT followed by regular face to face therapy
(for those patients who are still fatigued and/ or disabled after cognitive
behavioural internet therapy) as efficient (i.e. required number of sessions
and therapist time per patient and for quality adjusted life years) as care as
usual i.e. CBT following the waiting list?

The first part of this study consists of an open randomised controlled
intervention study comparing the efficacy of CBIT (protocol driven feedback or
support on demand) with a waiting list condition. Patients are only blind for
the type of CBIT they are allocated to (protocol driven feedback versus support
on demand). We hypothesized patients will behave differently if they would know
that the level of feedback is manipulated.

The second part of this study will consist of a randomised controlled
non-inferiority trial testing if CBIT followed by face to face CBT (for those
patients who still are fatigued and/or disabled following CBIT) is non-inferior
to care as usual (waiting list followed by face to face cognitive behaviour
therapy).

Patients allocated to the CBIT learn how to change fatigue perpetuating
cognitions and behaviour. The treatment is based on the protocol for individual
face to face cognitive behavioural therapy. The cognitive behavioural model for
CFS assumes there is a trigger for fatigue which does not account for the
fatigue to perpetuate. According to the model the fatigue is perpetuated by
behaviours and cognitions. By changing these, the fatigue and disabilities will
decrease. There are 2 intervention conditions in the first phase of the study:

CBIT with protocol driven feedback.
During 6 months in which patients receive information and make assignments
patients will receive weekly feedback from their therapist. This feedback
consists validation of their progress and suggestions/ advice. Feedback will be
given (at least) within 5 workdays counted from the date of the patient*s
reaction. During the treatment of 6 months the feedback become less frequent
(once to two-weekly) following the same frequency of contact as face to face
therapy.

CBIT with support on demand.
Patients in the support on demand condition will follow the same internet
therapy. Patients can ask for support or feedback by sending an email to the
therapist. Then, feedback will (also) be given within 5 workdays after the
email/ message send by the patient. Feedback will be given in the same way as
in the protocol driven feedback condition.

If patients do not profit enough from the CBIT, regular face to face
CBT-treatment will be offered with a maximum duration of 6 months and 12-14
session. CBT is offered when patients are still severely fatigued (CIS-fatigue
> 35) and/or disabled (SIP total >700) following the CBIT or waiting list.

Previous research has shown there are no detrimental effects of CBT for CFS
[11] and guided self instructions. There were no adverse events reported in the
study testing a CBIT in adolescent CFS patients[7]. There are also no specific
risk factors associated with the CBIT for CFS and the burden for patients is
limited. Patients who participate in the waiting list condition will receive an
extra asked assessment compared to patients who not participate in this study.
Patients in the waiting list condition will not wait longer than usual before
they start with individual CBT for CFS. Because many patients are referred to
the Expert Centre Chronic Fatigue for treatment the waiting period for starting
treatment is 6 months. The waiting period is due to a limited treatment
capacity. The benefit of participating in this study when a patient is
allocated to the CBIT starting directly with (internet) therapy instead of
waiting half a year before CBT starts.