Inference Based Approach (IBA): towards personalized care for OCD patients ;A randomized non-inferiority controlled trial into the effectiveness and working mechanisms of IBA in comparison to CBT.

Obsessive-Compulsive Disorder (OCD) is one of the most disabling psychiatric
disorders. However, the standard psychotherapeutic treatment Cognitive
Behavioral Therapy (CBT) is unable to redeem about half of all patients and is
rejected by many because of its anxiety provoking methods. A promising
alternative is the Inference Based Approach (IBA), which appears to be as
effective as CBT, and possible more effective for patients with limited
insight. The current study will investigate the proposed IBA non-inferiority to
CBT, in order to offer patients this much needed alternative. Furthermore, we
will investigate the neurobiological working mechanisms of both treatments.
Both treatment modalities are expected to alter the connectivity within and
between different functional networks. In order to lead the way towards
personalized care for OCD sufferers, we will search for clinical and
neurobiological predictors of response to both treatment modalities. By
predicting on forehand whether an individual patient will respond better to IBA
or CBT, we aim to prevent the demoralizing effect of undergoing ineffective
treatment.

Primary Objectives:
- Is IBA non-inferior to CBT in treating patients with OCD?


Secondary Objectives:
-* Does treatment modality predict pre- to posttreatment changes in neural
networks, and is this related to symptom reduction and changes in cognitive
performance?
- Do pre-treatment neural network patterns have predictive value for
treatment response?
- Is IBA superior to CBT in treating patients with poor insight?
- Is IBA more tolerable than CBT for patients with OCD?
- What are clinical and demographic predictors of treatment outcome?
- Does insight improve more or earlier in patients who underwent IBA,
compared to those who underwent CBT? Is change in insight related to symptom
reduction?

The current study is a multicenter, randomized controlled non-inferiority
trial. During 130 weeks, we will recruit 203 OCD patients fulfillling in- and
exclusion criteria. During intake for treatment at one of the participating
specilized clinical care units, patients will be informed about the study and,
if interested, receive the patient information letter. They will be contacted
at least one week later by the local study coordinator, providing sufficient
time to consider participation. If they are willing to participate, they will
be invited for a baseline visit, during which the in- and exclusion criteria
will be assessed. The patient will subsequently be randomized to either 20
sessions IBA or 20 sessions CBT. The randomization ratio is 1:1, stratified by
site. OCD symptom severity will be assessed by a blind assessor during
baseline, after 10 sessions, after all 20 sessions, and during two follow-up
visits (6 and 12 months after posttest). Patients will rate the severity of OCD
and insight in OCD with weekly questionnaires.

In order to explore working mechanisms of both treatment modalities, 43
patients of each treatment arm will receive pre- and posttreatment brain
imaging and neuropsychological assessment at the VU medical center in
Amsterdam. After randomization, interested patients are screened for MRI
eligibility, until we have reached the sufficient amount of participants.
Additionally, 43 healthy controls will receive a single brain imaging and
neuropsychological testing session to allow for comparison with OCD patients.

The IBA treatment, a focused form of psychotherapy consists of twenty
45-minutes sessions, delivered weekly and carried out as specified in a
session-by-session IBA protocol, containing standardized forms for exercises
and homework assignments that was translated into Dutch. Each session has a
standard format, starting with agenda setting and evaluating homework
assignments, followed by determining and executing a new exercise and
determining new homework. The IBA model is based on the assumption that
patients with OCD feel the need to perform compulsive acts because they
misjudge the actual state of affairs. It is assumed that certain reasoning
processes lead to these erroneous conclusions and distract the patient*s
attention from observable reality.

The IBA treatment teaches patients how to defend themselves against the
absorbing and confusing effect of obsessive reasoning processes and how to stay
in touch with reality by actively relying on the sensory information of the
very moment. As a consequence, the patient realizes that any compulsive act is
superfluous and feels able to omit it.

No negative side effects of undergoing CBT, IBA and MRI scanning are known. The
burden of participating will mainly consist of an extra time investment.


Anticipated risk factors:
1. Distress from receiving IBA treatment
Subjects may experience distress, anxiety or fatigue during IBA treatment,
which can be expected by undergoing any form of psychotherapy. However, we
expect no additional risk factors when compared to CBT, the standard clinical
care. In fact, we expect IBA to be more tolerable than CBT, because it does not
use anxiety provoking methods.
2. Distress from study assessments
Before, during and after treatment, an independent assessor will discuss
emotional symptoms with the participant. This may be confronting and could
cause distress. However, this does not exceed treatment as usual procedures.
3. Risks associated with Magnetic Resonance Imaging
MRI Scanning on 3Tesla MRI Scanners can be classified as a non-significant risk.

Procedures to minimize risks:
1. Distress from receiving IBA treatment
IBA treatment will be performed by experienced clinicians, who are well trained
in recognizing and handling distress, anxiety and fatigue. Additionally,
clinicians will participate in an intensive 4-day during IBA training, to
ensure proper conducting of the treatment. Participants are carefully monitored
during every study phase and encouraged to report any discomfort.
2. Distress from study assessments
All assessors will be extensively trained to recognize signs of distress. To
minimize any potential distress from discussing emotional symptoms,
participants are told they may move to the next question, if any makes him/her
uncomfortable. Breaks will be offered in between measurements to reduce
fatigue.
3. Risks associated with Magnetic Resonance Imaging
A thorough safety screening (e.g. metal screening) will be performed before
entering the MRI room. No other precautions are necessary, given the
classification as a non-significant risk.