Evaluating the Effectiveness of Imagery Focussed Therapy in Patients Suffering From Bipolar Disorder: an Exploratory Trial
Phase: NA
Conditions: Bipolar Disorder
Sponsor: Maastricht University

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RESEARCH PROTOCOL 
 
Evaluating the Effectiveness of Imagery 
enhanced Cognitive Therapy 
 
 

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PROTOCOL TITLE: Evaluating the effectiveness of imagery focussed cognitive therapy in 
patients suffering from bipolar disorders: An exploratory trial 
 
Protocol ID 
NL64193.068.18 / METC183005 
Short title 
Evaluating the Effectiveness of Imagery enhanced 
Cognitive Therapy 
 
EudraCT number  
NA 
Version 
2 
Date 
April 2018 
Coordinating investigator/project 
leader 
 
Karin van den Berg 
Klinisch psycholoog 
(buiten) promovendus Maastricht University 
karin.vandenberg@maastrichtuniversity.nl 
31651686505 
Principal investigator(s) (in 
Dutch: hoofdonderzoeker/ 
uitvoerder) 
<Multicenter research: per site> 
 
Prof. dr. G.P.J. Keijsers 
Clinical Psychological Science 
Faculty of Psychology and Neuroscience 
g.keijsers@psych.ru.nl 
ger.keysers@maastrichtuniversity.nl 
06-28510208 
 
 
Sponsor (in Dutch: 
verrichter/opdrachtgever) 
Maastricht University 
Clinical Psychological Science 
Faculty of Psychology and Neuroscience 
 
 
Subsidising party 
NA 
Independent expert (s) 
Dr. S. Valentijn 
Afdeling Psychiatrie en Medische Psychologie 

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Catharina ziekenhuis Eindhoven 
susanne.valentijn@catharinaziekenhuis.nl 
040-239900 
 
 
 
 
Laboratory sites <if applicable> 
NA 
 
 
Pharmacy <if applicable> 
NA 
 
 

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PROTOCOL SIGNATURE SHEET 
 
Name 
Signature 
Date 
Sponsor or legal representative: 
<please include name and 
function> 
 
 
Prof. Dr. G.P.J. Keijsers 
Clinical Psychological Sciences 
Faculty of Psychology and 
Neuroscience 
g.keijsers@psych.ru.nl 
Ger.keijsers@maastrichtuniversity.nl 
06-28510208 
 
 
 
 
 
[Coordinating Investigator/Project 
leader/Principal Investigator]: 
<please include name and 
function> 
 
 
 
 
 
 
 
Prof. Dr. G.P.J. Keijsers 
Clinical Psychological Sciences 
Faculty of Psychology and 
Neuroscience 
g.keijsers@psych.ru.nl 
Ger.keijsers@maastrichtuniversity.nl 
06-28510208 
 
 
 

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TABLE OF CONTENTS 
 
1. 
INTRODUCTION AND RATIONALE ............................................................................. 10 
2. 
OBJECTIVES ............................................................................................................... 11 
3. 
STUDY DESIGN ........................................................................................................... 13 
4. 
STUDY POPULATION .................................................................................................. 14 
4.1 
Population (base) ................................................................................................... 14 
4.2 
Inclusion criteria ..................................................................................................... 14 
4.3 
Exclusion criteria .................................................................................................... 14 
4.4 
Sample size calculation ......................................................................................... 15 
5. 
TREATMENT OF SUBJECTS ...................................................................................... 16 
5.1 
Investigational product/treatment ........................................................................... 16 
5.2 
Use of co-intervention (if applicable) ...................................................................... 17 
6. 
METHODS .................................................................................................................... 18 
6.1 
Study parameters/endpoints .................................................................................. 18 
6.1.1 
Main study parameter/endpoint....................................................................... 18 
6.1.2 
Secondary study parameters/endpoints (if applicable) .................................... 18 
6.2 
Randomisation, blinding and treatment allocation .................................................. 20 
6.3 
Study procedures ................................................................................................... 20 
6.3.1 Screening procedures………………………………………………………………………   20 
6.3.2 Study Assessment Moments ………………………………………………………………..21 
6.3.3 Assessment Procedures……………………………………………………………………. 21 
6.4 
Withdrawal of individual subjects ........................................................................... 21 
6.4.1 
Specific criteria for withdrawal (if applicable) ................................................... 21 
6.5 
Replacement of individual subjects after withdrawal .............................................. 21 
6.6 
Follow-up of subjects withdrawn from treatment .................................................... 22 
6.7 
Premature termination of the study ........................................................................ 22 
7. 
SAFETY REPORTING .................................................................................................. 22 
7.2 
AEs, SAEs and SUSARs ....................................................................................... 22 
7.2.1 
Adverse events (AEs) ..................................................................................... 22 
7.2.2 
Serious adverse events (SAEs) ...................................................................... 22 
7.3 
Follow-up of adverse events .................................................................................. 23 
7.4 
[Data Safety Monitoring Board (DSMB) / Safety Committee] .................................. 23 
8. 
STATISTICAL ANALYSIS ......................................................................................... 23 
9. 
ETHICAL CONSIDERATIONS .................................................................................. 26 
9.1 
Regulation statement ............................................................................................. 26 
9.2 
Recruitment and consent ....................................................................................... 26 

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9.3 
Compensation for injury ......................................................................................... 27 
9.4 
Incentives (if applicable) ........................................................................................ 27 
10. 
ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION ......................... 27 
10.1 
Handling and storage of data and documents ........................................................ 27 
10.2 
Monitoring and Quality Assurance ......................................................................... 28 
10.3 
Amendments ......................................................................................................... 28 
10.4 
Annual progress report .......................................................................................... 28 
10.5 
End of study report ................................................................................................ 28 
10.6 
Public disclosure and publication policy ................................................................. 29 
11. 
STRUCTURED RISK ANALYSIS .............................................................................. 29 
11.1 
Synthesis ............................................................................................................... 29 
12. 
REFERENCES .......................................................................................................... 30 

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LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS  
 
ABR 
ABR form, General Assessment and Registration form, is the application 
form that is required for submission to the accredited Ethics Committee (In 
Dutch, ABR = Algemene Beoordeling en Registratie) 
AE 
Adverse Event 
CCMO 
Central Committee on Research Involving Human Subjects; in Dutch: 
Centrale Commissie Mensgebonden Onderzoek 
CV 
Curriculum Vitae 
DSMB 
Data Safety Monitoring Board 
EU 
European Union 
GCP 
Good Clinical Practice 
IC 
ImCT 
CBT 
Informed Consent 
Imagery based Cognitive Therapy 
Cognitive Behavioural Therapy 
METC  
Medical research ethics committee (MREC); in Dutch: medisch ethische 
toetsing commissie (METC) 
(S)AE 
(Serious) Adverse Event  
Sponsor The sponsor is the party that commissions the organisation or performance 
of the research, for example a pharmaceutical 
company, academic hospital, scientific organisation or investigator. A party 
that provides funding for a study but does not commission it is not 
regarded as the sponsor, but referred to as a subsidising party. 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
Wbp 
Personal Data Protection Act (in Dutch: Wet Bescherming Persoonsgevens) 
WMO 
Medical Research Involving Human Subjects Act (in Dutch: Wet Medisch-
wetenschappelijk Onderzoek met Mensen 
 
 

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SUMMARY 
 
Rationale: Bipolar disorder is a severe, chronic mental illness with currently limited treatment 
options, both cognitive behavioural therapy (CBT) and pharmacological treatment have 
modest effects. There is consensus for the need to improve effectiveness of cognitive 
behavioural therapy (CBT) for patients suffering from bipolar disorders. As for many other 
mental disorders specific treatments have been improved using imagery, and imagery 
appears to play a causal role in mood variability in bipolar disorders, adding imagery 
interventions to CBT might aid this aim. This feasibility study elaborates on a pilot study by 
Holmes (Holmes et al., 2016) and an audit (Hales et al., 2018) by comparing a new imagery 
enhanced cognitive behavioural therapy (ImCT) to psychoeducation treatment to evaluate 
the effectiveness of ImCT with an aim to inform a large planned RCT evaluating ImCT. 
Objective: This study aims to evaluate the effectiveness of a new imagery enhanced 
cognitive behavioural therapy (ImCT) for patients suffering from bipolar disorders, by 
comparing ImCT to psychoeducation, one of the most regularly applied psychological 
interventions for bipolar disorder. 
Study design: This study is a randomised feasability trial, comparing ImCT intervention to 
psychoeducation. In addition to the between group design, we will also use a within-group 
design were ImCT or psychoeducation is preceded by and compared to baseline condition.  
Study population: Patients between 18 and 68 years old, suffering from bipolar disorders, in 
care at a specialised centre for bipolar disorders (Centrum Bipolair) from a large psychiatric 
hospital (GGzE), having regular contact with their psychiatrist on medication advise.  
Intervention: One group receives a new imagery enhanced cognitive behavioural therapy 
(ImCT), successfully piloted in a case series design in previous research (Holmes et al., 
2016). The other group receives psychoeducation treatment. Both interventions consist of 12 
hours active treatment and both interventions are carried out conform existing protocols. 
During the course of the study both groups keep receiving their regular consultation with a 
psychiatrist (to advise, monitor and if necessary adjust) for mood stabilising medication.  
Main study parameters/endpoints: The primary outcome variable is changes in mood 
variability. The secondary outcome variables are changes in levels of depression, mania, 
anxiety, general level of functioning and level of hopelessness, number of relapses into 
mania and depression and changes in imagery characteristics.  
Nature and extent of the burden and risks associated with participation, benefit and 
group relatedness: Risks for patients participating in this study are minimal. ImCT 
intervention has been successfully tested in a pilot study (Holmes et al., 2016) and an audit 
(Hales et al., 2018), suggesting this intervention is able to decline mood variability in patients 
suffering from bipolar disorder, and is also well tolerated and well received by patients. The 

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psychoeducation intervention closely resembles care as usual but is during this study 
delivered more structured by using a protocol. All patients, during the baseline period, during 
both treatments and during the follow-up period have regular appointments with their 
psychiatrist, who prescribes, monitors and adjusts mood stabilising medication. Should 
patients relapse into mania or depression, they will receive standard care as usual. Both 
interventions, ImCT and psychoeducation treatment are carried out conform existing 
protocols. The extra burden for patients, is the weekly questionnaires (20 minutes), and the 
questionnaires at T0-T4 (45 minutes), as daily mood monitoring is advised in current 
guidelines and part of care as usual.  
 

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1. INTRODUCTION AND RATIONALE 
 
The DSM 5 defines bipolar disorder as a chronic and severe condition characterised 
by episodes of extreme moods, mania (or hypomania) and depression (Association, 2013). 
Bipolar disorder afflicts 1.9% to 2.4% of the general population (Regeer et al., 2004; ten 
Have, Bijl, & Nolen, 2002). In addition, bipolar disorder is associated with high inter episode 
distress and with ongoing mood swings (mood variability), high suicide risk, and high co-
morbidity with other mental health problems especially anxiety (McElroy et al., 2001; Simon 
et al., 2004). Current interventions consist of pharmacotherapy and psychological 
interventions, predominantly psycho-education and cognitive behaviour therapy (CBT). 
Despite these interventions, 50% of patients do not recover within one year, only 25% 
achieve full recovery (Leahy, 2007) , and 60% relapse again within two years (Geddes & 
Miklowitz, 2013). There is a consensus for the need to update CBT interventions and 
increase its effectiveness, aiming at not only managing symptoms, but also at targeting 
perpetuating or precipitating factors.  
In a recent experimental study, O’Donnel and colleagues (O'Donnell, Di Simplicio, 
Brown, Holmes, & Burnett Heyes, 2017) showed that mental imagery might play a causal 
role in mood changes in patients suffering from bipolar disorders. Their findings are in line 
with ideas of Holmes and colleagues, proposing that mental imagery can act as an 
“emotional amplifier”, thus driving mood changes (Holmes, Coughtrey, & Connor, 2008; Ng, 
Di Simplicio, & Holmes, 2016). Furthermore, experimental research showed that imagery has 
a greater effect on emotion (Holmes & Mathews, 2005; Holmes, Mathews, Dalgleish, & 
Mackintosh, 2006) and behaviour (Libby, Shaeffer, Eibach, & Slemmer, 2007) than verbal 
cognitions. 
Mental imagery is considered a transdiagnostic feature of mental disorders 
(DiSimplicio et al., 2016; Holmes, Arntz, & Smucker, 2007) and added imagery interventions, 
enhanced the effectiveness of several cognitive behavioural interventions For example 
updating appraisals of imagery has helped improve effectiveness of CBT for social phobia 
(Wild & Clark, 2011), targeting vividness of imagery during exposure and EMDR helped 
improve CBT treatment in patients suffering from PTSD (Ehlers, Clark, Hackmann, 
McManus, & Fennell, 2005). These findings suggest that adding imagery interventions might 
also improve CBT for bipolar disorder.  
In 2016 Holmes and colleagues (Holmes et al., 2016) introduced a brief imagery-
based cognitive intervention (ImCT) for patients suffering from bipolar disorder, using 
techniques aimed at both, quality of the imagery and appraisals of the imagery. ImCT is a 
promising intervention as it allows for flexible fine-tuning to target specific elements of 
imagery. ImCT incorporates an elaborate micro-formulation of imagery (teasing out both 

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qualitative aspects of imagery as well as appraisals), followed by metacognitive intervention, 
imagery rescripting or positive imagery and competing task (or a combination of these), 
tailoring the intervention depending on the outcome of the micro formulation. Holmes and 
colleagues (Holmes et al., 2016) conducted a pilot study using a non-concurrent baseline 
design, with a series of A-B replication. Fourteen patients with bipolar disorder were 
randomly assigned to 4, 5, or 6 weeks baseline after which they received ImCT (in total 10 to 
14 sessions). Outcome measures were weekly measures of mood (mania, depression, and 
anxiety) and changes in targeted imagery. In addition, daily mood measures were collected 
using a smart phone text messaging to accurately measure mood variability. Result showed 
that patients reported an increase in mood stability, as well as improvements on weekly, and 
pre- and post-measures of mood and target imagery. Moreover, it is important to note that 
this study concluded that daily measurements were feasible. All in all, ImCT appears 
promising for bipolar disorder and invites further evaluation. 
In the present research proposal, we elaborate on the previous ImCT pilot study 
(Holmes et al., 2016), comparing its effectiveness in patients with bipolar disorder to 
psychoeducation treatment. As noted before psychoeducation treatment is one of the most 
regularly applied psychological intervention for bipolar disorder. In advance of a large 
upcoming RCT in the UK it is necessary to derive more precise estimates of retention rates, 
especially on daily monitoring, and information on general feasibility as well as first data 
comparing ImCT to an appropriate control condition. We propose a randomised controlled 
feasibility study, comparing the effects of ImCT to psychoeducation in patients suffering from 
bipolar disorder in patients who standard have regular appointments with their psychiatrist, 
prescribing, monitoring and adjusting mood stabilising medication in a specialized bipolar 
treatment centre. 
 
2. OBJECTIVES 
 
Primary Objective and secondary objectives:  
 
The present  research project elaborates on a pilot study by Holmes and colleagues (2016) 
and an audit (Hales et al., 2018) using a new cognitive behavioural therapy enhanced with 
imagery techniques (ImCT), with an aim to improve the effectiveness of CBT for patients 
suffering from bipolar disorder. The pilot study (Holmes et al., 2016) found promising 
treatment effects but a controlled feasibility study is needed to test whether this treatment is 
more effective than regular treatment. Therefore, this research projects examines the effect 
of this new ImCT treatment, by comparing this intervention to psychoeducation treatment, 
one of the most regularly applied psychological intervention for bipolar disorder. The current 

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study will provide new insights for an upcoming large RCT evaluating the effectiveness of 
ImCT in the UK. 
 
Our primary objective is to estimate the effects of ImCT compared to psychoeducation on 
mood variability. We hypothesise that (1) mood variability (primary outcome variable) will 
show stronger decreases in BD patients receiving ImCT at end of the intervention (T2), at 
follow-up measurement  8 weeks after concluding the interventions (T3) and at follow-up 
measurement 16 weeks after concluding the interventions (T4) than psychoeducation. 
Additionally, the effects of both treatments separately are also compared to baseline period 
preceding both treatments.  
 
Our secondary objective is to estimate the effect of ImCT compared to psychoeducation on 
1) level of depression, mania and anxiety and 2) general functioning and level of 
hopelessness (secondary outcome variables), 3) number of relapses into mania or 
depression and 4) changes in imagery characteristics. We hypothesise that (2a) symptoms 
of depression, mania and anxiety decrease and (2b) general functioning increase and level 
of hopelessness decrease (secondary outcome variables) more strongly in BD patients 
receiving ImCT than psychoeducation at T2, T3 and T4. Additionally, the effects of both 
treatments separately are also compared to baseline period preceding both treatments.  
We also hypothesise that 3) number of relapses into mania or depression after the end of 
ImCT are lower in the ImCT condition during the follow up period (T4) than in the 
psychoeducation condition. Finally, we hypotheses that 4) imagery characteristics will 
change more and problematic imagery decreases in the BD patients receiving ImCT at T2, 
T3 and T4, compared to baseline. 
 
Note that, our primary outcome variable, mood variability, is measured in two ways. First, at 
baseline (T0), pre-intervention (T1), T2, T3 and T4. Second, mood variability is measured 
daily, during the four weeks baseline, during the intervention, and during the follow-up period 
(in total 16 weeks post intervention), in both the ImCT and psychoeducation conditions.  
Further note that the secondary outcome variables (2a), level of depression, mania and 
anxiety, are measured weekly throughout the duration of the study in both conditions and the 
secondary outcome variables (2b) general functioning and level of hopelessness and (4) 
changes in imagery are only measured at T0, T1, T2, T3 and T4. All measures are 
administered using an online secure server called Research Manager.  
 
 

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3. STUDY DESIGN 
 
The present research proposal concerns a randomised feasibility trial, comparing ImCT 
intervention to psychoeducation. In addition to the between group design, the study also 
uses a within-group design, were ImCT and psychoeducation is preceded by a four-week 
baseline condition. Note that during this baseline period and throughout the study, all 
patients will maintain their regular appointments with their psychiatrist or specialised nurse 
practitioner, who will prescribe, monitor and adjust mood stabilising medication conform 
guidelines. The within-group design allows participants baselines to act as their individual 
control periods with no intervention (Barlow, Nock, & Hersen, 2009; Bonsall, Wallace-Hadrill, 
Geddes, Goodwin, & Holmes, 2012; Holmes et al., 2016). The study will take place within a 
specialised centre for bipolar disorders within a large psychiatric hospital (GGzE). All 
participants start after 4 weeks of baseline with either ImCT or psychoeducation treatment 
The duration of the study for participants will be 32 weeks for participants in the ImCT 
condition and 26 weeks for participants in the psycho-education condition. The difference in 
duration between the conditions is due to treatment length, that is, 12 weeks weekly 1-hour 
sessions for ImCT and 6 weeks weekly 2-hour sessions for the psychoeducation treatment. 
Note that all participants will have had 12 hours face-to-face contact in both conditions. 
 
Recruitment  in Centrum Bipolair GGzE 
 
Informed Consent 
v 
Screen for eligibility 
Baseline assessments and start  
with 4 weeks daily measurements 
RandomisaAon 
ImCT 
PsychoeducaAon 
Pre-intervenAon measurements 
Daily measurements 
Weekly assessments 
Post-intervenAon measurements 
Follow up (8 & 16 weeks) 
Pre-intervenAon measurements 
Daily measurements 
Weekly assessments 
Post-intervenAon measurements 
Follow up (8 & 16 weeks) 
 

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4. STUDY POPULATION 
4.1 Population (base)  
Participants will be recruited from a specialised centre for bipolar disorders of a large 
psychiatric hospital (GGzE, Centrum Bipolaire stoornissen). All patients who are referred to 
this service and all patients who 1) did not receive the current or a largely comparable 
psychoeducation program 1 year prior to start of the study and 2) who did not receive CBT-
treatment tailored for bipolar disorder and with or without imagery interventions 1 year prior, 
are given written and oral information and informed consent forms and are invited to 
participate in this study. Currently there are 400 patients attending this service, at least 300 
of those have not had psychoeducation or CBT in the last year. On average 70 new patients 
are referred to this specialised centre each year. Patients attending this service are aged 
between 18 and 65 years old, both male and female, mostly white European.  
 
4.2 Inclusion criteria 
In order to be eligible to participate in this study, a subject must meet all of the following 
criteria: 
 
• 
Aged 18-68 
• 
Sufficient Dutch language ability to permit the assessment to be completed. 
• 
Diagnosis of BD (I or II or unspecified) according to DSM-5 (clinicians assessment). 
• 
Willing to complete daily and weekly monitoring throughout the duration of the study. 
• 
Successful completion of the daily monitoring in the 4 weeks active run-in phase. 
• 
Willing to be randomised to either ImCT or psychoeducation condition 
• 
Able to attending 12 consecutive weekly sessions ImCT or 6 weekly two hours 
sessions psychoeducation/TAU. 
 
4.3 Exclusion criteria 
A potential subject who meets any of the following criteria will be excluded from 
participation in this study: 
 
• 
Learning difficulties, organic brain disease or severe neurological impairment. 
• 
Have received either 1) psychoeducation similar to the presently used 
psychoeducation program, or 2) CBT tailored at bipolar disorder with or without 
imagery interventions within the last year prior to the start of the study. 
• 
Current severe substance or alcohol misuse (clinicians assessment). 

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• 
Current manic episode as diagnosed by DSM-5 
• 
Current active psychotic symptoms 
• 
Presence of active suicidal risk as indicated by a score of 2 or more on item 12 (i.e. 
frequent thought and/or plans to end their life) of the QIDS (Rush et al., 2003) 
confirmed by convergent clinical opinion. 
• 
Taking part in concurrent treatment studies investigating pharmacological or 
psychological treatment for BD. 
 
4.4 Sample size calculation 
To estimate the sample size needed for the between group design of this study, we used the 
study’s primary outcome variable, mood variability, which is measured using the Affect 
Lability Scale (ALS-18). 
 
The primary outcome variable for the between subjects design of the study, is the ALS-18, 
which was used in the audit (Hales et al., 2018) and in the pilot study by Holmes (Holmes et 
al., 2016). The effect sizes they found using the ALS-18 were d = 0.8 and d = 0.99 (see 
Table 1 below). We expect similar effect sizes in our study, that is d = 0.9 (the mean of the 
prior mentioned studies). Studies on the effect of psychoeducation have shown only 
moderate effects on medication adherence, knowledge of bipolar disorder and attitudes, but 
no or limited effect on mood variability or relapse, ranging from no effect (Bond & Anderson, 
2015; Kurdal, Tanriverdi, & Savas, 2014) to a minimal effect (maximum of d = 0.3, but only in 
patients with less than 7 episodes), (Gumus, Buzlu, & Cakir, 2015; Morriss et al., 2016). We 
therefore expect an effect size of d = 0.6 (i.e., d = 0.9 minus d = 0.3). Based on prior 
mentioned effects of the ALS-18 we calculated the sample size needed, to power this study 
at 80% to detect an effect size of Cohen’s d = 0.6 using a significance level of.05 two tailed 
T-tests using G*power 3.1.9.3 The calculated sample size needed is 45 in each group.   
The study of Holmes et al. (2016) showed a drop out 1 out of 15. After consulting with the 
research group from the audit and pilot study we expect a similar drop out rate in the current 
study. We therefore need a sample size of 48 in each group, 96 in total.  
 
Table 1: Mean (SD) ALS-18 scores before and after ImCT in the pilot study of (Holmes et al., 
2016) 
Pre- 
Treatment 
 
End of 
Treatment 
 
4 week FU 
 
12 week FU 
 
24 week 
FU 
 
Time 
Pairwise differences, 
Bonferroni corrected pairwise 
t-test 
46.36 
(11.26) 
35.54 
(10.49) 
35.43 
(10.92) 
36.36 
(12.58) 
34.71 
(12.74) 
F(4.48)= 6.75, 
p<.001 
Pre vs 4w t(12)= 3.77, p 
=.027, d=0.99; pre vs 12w 

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t(12)=3.58, p=.038, d =.84; pre 
vs 24w t(12)=4.62, p =.006, d 
= 0.97 
 
Next to the ALS-18 as primary measure, we also use daily mood variability scores, using the 
NIMH-LCM, for the within subjects-design. Here the assessment are comparted between 
baseline (4 weeks is 28 measuring points) conditions and both treatment conditions (at least 
6 weeks is 42 measuring points). As we use 70 measuring points in total only a small number 
of cases suffices to calculate and test differences scores. That is, for such a case series 
analyses, a sample size of 4 or more is sufficient (Barlow et al., 2009). Moreover, Bulte and 
Onghena (Bulte & Onghena, 2009) stress that to achieve a large effect size (d = 1.5) and a 
study powered at 80%, a study would need a minimum of 4 participants with a minimum of 
20 measurements per person. Our study meets those requirements. 
 
Finally, it is important to note that this is a feasibility study following an audit on ImCT (Hales 
et al., 2018), and a pilot study on ImCT (Holmes et al., 2016), and precedes and plans to 
inform a large upcoming (N = 350) RCT on ImCT in the UK next year. The National Institute 
for Health Research recommend sample sizes for a feasibility study of 30 in total (15 per 
arm) or a range of 24 to 50 in total (12 to 25 per arm) (Julious, 2005; Lancaster, Dodd, & 
Williamson, 2004; Sim & Lewis, 2012). Our study also meets those requirements. 
 
 
5. TREATMENT OF SUBJECTS 
 
5.1 Investigational product/treatment 
 
Both ImCT and psychoeducation interventions are preceded by a period of 4 weeks baseline, 
in which they start to monitor their mood both daily and weekly, start or continue sessions 
with a psychiatrist (see below). Both groups will either start or continue to have regular 
sessions with their psychiatrist throughout the study, aimed at advice on pharmacotherapy, 
monitoring and if necessary adjustment of pharmacotherapy. 
 
Description of ImCT:  
The participants receive ImCT for a period of 12 weeks, 12 sessions of 60 minutes. This 
intervention consists of an in-depth identification (4 sessions) of images followed by imagery 
interventions, (6 sessions) and a consolidation phase (2 sessions) developed by Holmes, 
Young, Hales and DiSimplico and described in the ImCT manual (in press). The in-depth 

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identification consists of identifying problematic imagery, constructing a micro-formulation 
with the participant along the lines of regular CBT. In this micro-formulation, first triggers of 
problematic imagery are identified, then both quality and appraisals of this image are 
identified. Subsequent maladaptive behaviour and possible links with earlier experiences are 
described, as well as other maintaining factors. The imagery intervention consists of 
metacognitive imagery intervention, rescripting of imagery, promoting positive imagery or 
competing imagery tasks (or a combination of these). In addition, relapse prevention 
strategies are practiced before the end of this intervention. To increase treatment integrity, 
therapist in the ImCT condition receive weekly supervision from the Imagery Research group 
(from Oxford, London and Stockholm) via skype. Therapists are qualified psychologist 
carefully trained in ImCT. 
 
Detailed description of psychoeducation: 
The psycho-education lasts for a period of 6 weeks, consisting of 6 2-hour sessions. Psycho-
education is offered in groups, using the format described in by Postma and colleagues 
(Postma, Honig, & van Gent, 2008). In the first three sessions patients are receiving 
information on bipolar disorder, symptoms, prevalence, aetiology and mood stabilisers. The 
remaining sessions focus on (early) recognition of mood variations, and management or 
coping strategies. Finally, medication adherence strategies and relapse strategies are 
discussed. Nursing staff who run the psychoeducation groups are experienced in running 
these groups and carefully trained in the psychoeducation method according to guidelines 
from Trimbos. 
 
5.2 Use of co-intervention (if applicable) 
 
Both groups (ImCT and psychoeducation) maintain their regular consults with a psychiatrist 
or specialised nurse practitioner and receive advice and guidance on medication, which is 
monitored and adjusted conform guidelines (Goodwin et al., 2016; Kupka et al., 2015) 
throughout this study. These guidelines recommend using a mood stabiliser, with specific 
recommendation for additions in episodes of mania and depression. Where possible the 
above-mentioned guidelines will be adhered to unless individual circumstances warrant 
deviations from this. Consultation with the psychiatrist or specialised nurse practitioner will 
start (or continue should patients already be in care) during the baseline period, intervention 
period and follow-up period.   
 

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6. METHODS 
6.1 Study parameters/endpoints 
6.1.1 Main study parameter/endpoint 
To assess the primary endpoint of this study (1), decrease of mood variability,  mood 
variability is measured using the Affect Lability Score Short Version (ALS-18) (Oliver & 
Simons, 2004) at baseline (T0), pre- intervention (T1) and post intervention (T2), and at 
follow-up measurements at 8 (T3) and 16 weeks (T4) after treatment discontinuation in both 
the ImCT and psychoeducation conditions. The ALS-18 is a self-report scale measuring 
lability in affect and consists of 18 items. Ratings are made on a 4-point scale with a 
maximum score of 72. Scores range from A= very characteristic of me (4 points), to D= very 
uncharacteristic of me (1 point).  
 
In addition we monitor changes in mood variability using the National Institute of Mental 
Health Life Chart Methodology (NIMH-LCM) Prospective Self-Rating (Denicoff et al., 2000). 
Participants rate their mood (both mania and depression) on a 9-point Likert scale, ranging 
from -4 (severe depression, admission required due to severe dysfunction) to 0 (stable 
mood) to +4 (severe mania, admission required due to severe dysfunction). Daily 
measurements are calculated during a 4-week baseline prior to start of either ImCT or 
psychoeducation, during the invention and until follow up at 16 weeks. This method is 
advised given that traditional self-report mood ratings over a single time point are scarcely 
representative of mood variability in bipolar disorder. 
 
6.1.2 Secondary study parameters/endpoints (if applicable): 
The following parameters are used for the following secondary objectives:  
 
To assess (2a) level of depression, mania and anxiety and (2b) general functioning and 
hopelessness (3) number of relapses into mania or depression decline/increase, we 
administer the following measures:  
 
- 
Level of depression, using the Quick Inventory of Depressive Symptoms (QIDS-SR) 
(Rush et al., 2003). The QIDS-SR is a 16-item self-report rating scale in which the 
nine DSM 5 symptoms of major depression are incorporated. Answers are rated on a 
four-point Likert scale (0-3). The QIDS-SR is administered weekly throughout the 
duration of the study. 

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- 
Level of mania, using the Altman Self-Rating Mania Scale (ASRM-NL) (Altman, 
Hedekker, & Peterson, 1997). The ASRM-NL is a 5 item self-report instrument to 
measure severity of mania symptoms. This is administered weekly throughout the 
duration of the study. 
- 
Level of anxiety, using the Beck Anxiety Inventory (BAI) (Osman, Barrios, Aukes, 
Osman, & Markway, 1993). The BAI is a 21-item self-report questionnaire used for 
measuring the severity of anxiety. Answers are rated on a 4-point Likert scale (0-3). 
This is administered weekly throughout the duration of the study. 
- 
Level of general functioning and coping: Participants rate their level of functioning 
using the Longitudinal Interval Follow up Evaluation – Range of Impaired Functioning 
Tool (Leon et al., 1999). This is a brief scale for people suffering from affective 
disorders, measuring four different functional areas (employment, interpersonal 
relations, satisfaction and recreation) on a 5-point Likert scale (low rating implies 
higher functioning). This is administered at T0, T1, T2, T3 and T4.   
- 
Level of hopelessness: participants rate their hopelessness using the Beck 
Hopelessness Scale (Beck, Brown, & Steer, 1997), The BHS is a 20 item self-report 
scale measuring three aspects of hopelessness: feelings about the future, motivation 
and expectations. The BHS demonstrates good internal consistency (alpha = .93) and 
has high reliability in psychiatric samples (Beck et al., 1997). The BHS is 
administered at T0, T1, T2, T3 and T4.   
- 
To assess number of relapses into mania and depression, scores on the above 
measures (ASRM for mania and QIDS-SR for depression) are used. Scores on the 
ASRM of 5 or more indicate a relapse into mania, a score of 10 or more on the QIDS 
a relapse into depression. This is measured using the weekly scores on the ASRM 
and QIDS-SR during the weekly measures in the follow up period (until 16 weeks 
after the end of either ImCT or psychoeducation). 
 
To assess if (4) problematic imagery the following measures will be used: 
• 
The Visual Analogue Scales of Imagery Characteristics (VAS-Imagery) have been 
tailored to BD populations. The scales range from 0-9. Examples are "How real / vivid 
/ absorbing / preoccupying / compelling have your image(s) been over the past 
week"; "To which extent could you understand the role that the image(s) play in your 
mood instability?"; "To which extent could you find positive / helpful way of using the 
image(s)?". Target imagery is measured weekly throughout the duration of the study. 
Imagery characteristics are measured weekly throughout the duration of the study in 
both ImCT and psychoeducation treatment conditions. 

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• 
Mental Imagery and Coping with Bipolar Disorder Questionnaire (MICQ-BD) is a 14 
item self-report instrument assessing patient’s response to mental imagery on a five-
point Likert scale, ranging from “not at all” to “a lot”. In a pilot study Holmes (2016) 
calculated the internal consistency (alpha = .70) of this measure to be satisfactory 
(DiSimplicio et al., 2016). General imagery is measured at T0, T1, T2, T3 and T4. 
• 
General Imagery (frequency of imagery, quality of imagery and appraisals of imagery) 
using the Dutch Imagery Survey, DImS): measured at T0, T1, T2, T3 and T4 using a 
42-item online Imagery Survey recently validated in a student sample (Van den Berg, 
in preparation), and patient samples (Van den Berg, in preparation).  
 
6.2 Randomisation, blinding and treatment allocation 
An independent central research assistant will randomize participants to treatment condition 
(ImCT or psychoeducation) after checking all in- and exclusion criteria. Randomization will be 
based on block randomization with (N=10) per block to guarantee a balance between 
conditions over time and stratified for mood stabilising medication (either mood stabilising 
medication, or no mood stabilising medication), so that mood stabilising medication is 
controlled per arm. Stratification for mood stabilising medication is necessary because not 
using mood stabilizing medication can seriously affect the primary outcome variable. We 
roughly estimate that 15 percent of the participants in GGzE will have no mood stabilising 
medication, but there are no firm data available. Blinding of participants and therapists to 
treatment condition is not possible in this kind of psychotherapy trial, but the assessments 
will be blind to treatment condition as they are filled in online. 
 
 
6.3 Study procedures 
6.3.1 
Screening procedures 
Patients are recruited from a specialised centre for bipolar disorders in psychiatric hospital 
(Centrum Bipolair GGzE). The responsible lead clinician (regie behandelaar) identifies 
eligible patients and subsequently give these patients the information letter as well as oral 
information about the study and asks permission to hand over their contact information to the 
researcher should they consider participating. Once patients have indicated to the 
researcher, their nurse, psychiatrist or psychologist they would like to participate in this 
study, the researcher makes an appointment with the patient. During this appointment the 
researcher checks if the identified patient meets the inclusion criteria, and if patients still 
agrees with participation in the study and they are given the informed consent letter. After 
one week in which patients can consider their participation in this study, the researcher 
makes another appointment with the participant during which both the researcher and 

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participant sign the informed consent letter. At this time, the researcher asks for the email 
address of the participants in order for the online questionnaires to be accessible for the 
patient. 
 
6.3.2 
Study Assessment Moments 
 
Psychoeducation groups at Centrum Bipolar start once in every six weeks. At four weeks 
prior to the start of each psychoeducation group the identified participants start with the 
online measures at baseline (T0), and both daily and weekly online measurements which 
participants receive by email. Note here that the patients that participate in this study will not 
wait longer than the patients that choose not to participate. Participants continue to fill in both 
the daily and weekly online measures for four weeks (the baseline period). After four weeks 
all participants fill in the measures pre-intervention (T1), and are allocated randomly to either 
the ImCT or psychoeducation condition, which will then commence. During the intervention 
period (12 weeks for the ImCT condition, and 6 weeks for the psychoeducation treatment 
condition) all participants continue to fill in both the daily and weekly online measures. At the 
end of the intervention, all participants fill in the post-intervention measures (T2) online. 
Subsequently, all participants continue to fill in both daily and weekly online measures until 
the end of the study (at follow up at 16 weeks). In addition, participants fill in the post-
intervention online measures at follow up at 8 weeks (T3) and 16 weeks (T4) after the end of 
intervention.   
6.3.3 
Assessment Procedures 
 
All measures are administered online. However, there is an option to fill in the questionnaires 
on paper, should this prove difficult for participants. The daily measures will take a 2 to 3 
minutes, the weekly measures will take approximately 20 minutes. The measures at baseline 
(T0), pre-intervention (T1), post-intervention (T2) and at 8 and 16-weeks follow-up (T3 and 
T4) will take approximately 45 minutes. Patients and therapist will not be informed about the 
results of assessments until the end of the study (16 weeks after the end of intervention).  
 
6.4 Withdrawal of individual subjects 
Subjects can leave the study at any time for any reason if they wish to do so without 
any consequences. The investigator can decide to withdraw a subject from the study 
for urgent medical reasons. 
6.4.1 Specific criteria for withdrawal (if applicable) 
If patients experience relapse (mania or depression) and require a hospital admission for 
longer than one week, they will be excluded from this trial. 
 

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6.5 Replacement of individual subjects after withdrawal 
Should patients withdraw from the study they will not be replaced. 
 
6.6 Follow-up of subjects withdrawn from treatment 
 
If patients are withdrawn from the study, they will continue with care as usual from the 
specialised centre for bipolar disorders of the GGzE.  
 
6.7 Premature termination of the study 
The study will be terminated if a large number of patients in ImCT condition drop-out or 
deteriorate. This, however, is not expected as the treatment has been piloted before and 
found highly effective and to have low drop-out rate.  
 
 
7. SAFETY REPORTING 
7.1 Temporary halt for reasons of subject safety 
In accordance to section 10, subsection 4, of the WMO, the sponsor will suspend the 
study if there is sufficient ground that continuation of the study will jeopardise subject 
health or safety. The sponsor will notify the accredited METC without undue delay of a 
temporary halt including the reason for such an action. The study will be suspended 
pending a further positive decision by the accredited METC. The investigator will take 
care that all subjects are kept informed.  
 
7.2 AEs, SAEs and SUSARs 
7.2.1 Adverse events (AEs) 
Adverse events are defined as any undesirable experience occurring to a subject 
during the study, whether or not considered related to the trial procedure or the 
experimental intervention. All adverse events reported spontaneously by the subject 
or observed by the investigator or his staff will be recorded. 
 
7.2.2 Serious adverse events (SAEs) 
A serious adverse event is any untoward medical occurrence or effect that:  
- 
Results in death; 
- 
Is life threatening (at the time of the event); 
- 
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- 
Admissions due to relapse episode mania or depression (part of routine care) 
- 
Results in persistent or significant disability or incapacity; 
- 
Is a congenital anomaly or birth defect; or 
- 
Any other important medical event that did not result in any of the outcomes listed 
above due to medical or surgical intervention but could have been based upon 
appropriate judgement by the investigator. 
 
The investigator will report all SAEs to the sponsor without undue delay after 
obtaining knowledge of the events, except for the following SAEs:  
- 
Relapse episode mania or depression as relapse is one of the secondary objectives 
of this study. 
 
 
The sponsor will report the SAEs through the web portal ToetsingOnline to the 
accredited METC that approved the protocol, within 7 days of first knowledge for 
SAEs that result in death or are life threatening followed by a period of maximum of 8 
days to complete the initial preliminary report. All other SAEs will be reported within a 
period of maximum 15 days after the sponsor has first knowledge of the serious 
adverse events. 
 
 
7.3 Follow-up of adverse events 
All AEs will be followed until they have abated, or until a stable situation has been 
reached. Depending on the event, follow up may require additional tests or medical 
procedures as indicated, and/or referral to the general physician or a medical specialist. 
SAEs need to be reported till end of study within the Netherlands, as defined in the 
protocol  
 
7.4 [Data Safety Monitoring Board (DSMB) / Safety Committee] 
 
In this study a DSMB is not needed, as the interventions consists of either care as usual, 
or a variation on care as usual. Relapse episodes (mania or depression) are expected as 
part of the condition. Appropriate care for this is in place and considered care as usual.  
 
 

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8. STATISTICAL ANALYSIS 
 
First, descriptive analyses will be used to establish mean scores, standard deviations and to 
identify outliers. Missing data from our primary outcome variable, will be listwise deleted. In 
our other outcome variables, data will only be included if pre- and post-measures are 
completed.  
Second, the data will be checked with respect to violation of assumptions (such as error 
independency, non-normal distributions) for variance-based models.  
 
Primary outcome variable: mood variability:  
 
To assess if there is a stronger decrease in mood variability in the ImCT intervention 
condition as compared to the psychoeducation condition, multivariate repeated measures 
analyses are applied. Dependent variables are the scores on the ALS-18 (baseline, T0; pre-
treatment, T1; post-treatment, T2; 8-weeks follow-up, T3; 16-weeks follow-up, T4) with 
treatment condition (ImCT, psychoeducation) as between subjects variable. 
In addition, to assess reductions in mood variability during  the interventions (ImCT, 
psychoeducation) compared to mood variability during the baseline period,  daily mood 
measures with the National Institute of Mental Health Life Chart Methodology (NIMH-LCM) 
Prospective Self-Rating of mood (both mania and depression) are assessed, using a case 
series design, were participants baseline ratings can act as their own control (Arntz, Sofi, & 
van Breukelen, 2013). Changes in mood variability are investigated using  sequence analysis  
with R-software (package TraMineR version 1.8-10); (Gabadinho, Ritschard, Muller, & 
Studer, 2011) on the daily scores. Sequences consist of a series of subsequent states (daily 
scores) and similarities between sequences are calculated with the Optimal Matching 
technique (OM). Sequences will be defined as day scores from 28 days prior to starting the 
interventions, until 112 days after the end of interventions. Rather homogenous groups of 
trajectories (clusters) will be derived from the distance matrix that result from the OM 
technique. To this end, cluster analysis will be applied. Shannon entropy of transversal state 
of the scores on each day will be calculated and plotted (Gabadinho et al., 2011). Entropy is 
a measure of diversity of states (a measure of mood variability) within sequences and varies 
between zero (all sequences in the same state) to 1 (maximum diversity). To explore the 
relationship between diversity in states (mood variability) and background characteristics, 
this longitudinal entropy will be regressed on co-variates (gender, medication). Also, 
sequences of scores at the start of treatment will be compared to subsequences during 
treatment and during the follow-up period to explore change over time. 

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Secondary outcome variables: depression, anxiety, mania, general functioning and 
coping, hopelessness, number of relapses into mania or depression, and changes in 
imagery: 
 
To assess if (2a) level of depression, mania and anxiety, (2b) general functioning and coping, 
and hopelessness increase/decline more in the ImCT intervention compared to 
psychoeducation treatment  two types of multivariate repeated measures analyses are 
applied, both with treatment condition (ImCT, psychoeducation treatment) as independent, 
between groups variable. In the first type of analyses, the dependent variables are the scores 
of the weekly measures for depression, anxiety and mania (QIDS-SR, BAI, ASRM). In the 
second type of analyses, time (T0, T1, T2, T3 and T4) is used as within between subject 
variables and scores of the same instruments and general functioning and coping and 
hopelessness (ALS-18, IFE-RIFT, BHS) are used as dependent variables.  
To assess if (3) number of relapse into mania or depression decline more in the ImCT 
intervention compared to psychoeducation treatment  Chi-square analyses are applied with 
as dependent variable number of relapses into mania or depression, using cut-of scores on 
the ASRM and QIDS-SR during the follow-up period and treatment condition (ImCT, 
psychoeducation treatment) as between groups variable. 
To assess if (4) problematic imagery decreases and imagery characteristics changes more 
by using the ImCT intervention compared to psychoeducation treatment, comparable to 2a 
and 2b, two types of multivariate repeated measures analyses are applied, both with 
treatment condition (ImCT, psychoeducation treatment) as between groups variable. In the 
first type of analyses, the dependent variables are the scores of the weekly measures of 
imagery (VAS). In the second type of analyses, time (T0, T1, T2, T3 and T4) is used as 
within between subject variables and scores of imagery (MICQ-BD and DIS) are used as 
dependent variables. 
 
Where possible multivariate analyses are used to analyse differences between groups, and 
repeated-measures ANOVA to analyse difference within groups. These will be used to 
minimise the correlations and dependencies between variables. In order to allow for reliable 
multivariate analysis, assumptions of sphericity are tested. Multivariate analyses between 
groups (ImCT, psychoeducation treatment) and repeated-measures ANOVA within groups 
(T0, T1, T2, T3, T4) are used to determine an omnibus effect. If differences are significant, 
post hoc analyses (mostly independent T-test) will be used to determine individual 
differences between groups and between points in time. Bonferoni corrections are used to 
correct for multiple testing.  

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Intention-to-treat analyses will constitute the central analyses and completers analyses will 
be done as supplementary analyses. 
 
9 
ETHICAL CONSIDERATIONS 
9.1 Regulation statement 
 
This study will be conducted according to the principles of the declaration of Helsinki  
(Brasil, 2013) and in accordance with the Medical Research Involving Human Subjects Act 
(WMO).  
 
9.2 Recruitment and consent 
 
Patients are recruited from a specialised centre for bipolar disorders in psychiatric hospital 
(Centrum Bipolair GGzE). The lead clinician (regie behandelaar) identifies eligible patients 
and subsequently give these patients the information letter as well as oral information about 
the study and asks permission to hand over their contact information to the researcher 
should they consider participating. Once patients have indicated to their nurse, psychiatrist or 
psychologist they would like to participate in this study, the researcher makes an 
appointment with the patient. During this appointment the researcher answers any remaining 
questions and if patients still agree with participation in the study they are given the informed 
consent letter. After one week in which patients can consider their participation in this study, 
the researcher makes another appointment with the participant during which both the 
researcher and participant sign the informed consent letter. At all times can patients withdraw 
from the study without explanation. Moreover, they have the opportunity to consult an 
independent expert (dr. S. Valentijn). Note that during the whole time that patients participate 
in this study they are allowed to continue or start with advice on mood stabilising medication 
from their psychiatrist.  
Once the researcher has obtained informed consent, baseline measures are administered. 
Patients start with four weeks daily mood measurements. At the end of these four weeks, 
they are randomly allocated to either ImCt or psychoeducation treatment condition and fill in 
the pre-intervention measurements online after which they start with either of both 
treatments. At the end of the treatments they fill in the post-intervention measurements 
online. At 8 and 16 weeks follow-up measurements the patients fill in measurements online. 
All patients continue their daily mood monitoring until follow-up at 16 weeks. Screening for 
eligibility ceases after 96 patients are included, 48 in each condition. 
 

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9.3 Compensation for injury 
 
The sponsor/investigator has a liability insurance which is in accordance with article 7 of 
the WMO.  
  
The sponsor (also) has an insurance which is in accordance with the legal requirements 
in the Netherlands (Article 7 WMO). This insurance provides cover for damage to 
research subjects through injury or death caused by the study. 
The insurance applies to the damage that becomes apparent during the study or within 4 
years after the end of the study. 
 
9.4 Incentives (if applicable) 
 
There is no special incentive, compensation or treatment that subjects will receive 
through participating in this study. However, participants will be reimbursed for their extra 
travel costs.   
 
 
10 ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION 
10.1 Handling and storage of data and documents 
 
All data are coded by means of number codes. Only the lead researcher has a key of 
names and participant numbers; the researchers of the research group of the project only 
get coded data, i.e., data with participant number, not with names. Codes are in 
chronological order, each subsequent participant is allocated the subsequent number. The 
participant data will be stored for up to 15 years after the last measurement of the last 
participant of this study. On the questionnaires used in this study is only the participant 
number visible, data is stored on a secure server, using Research Manager (which 
complies with the Dutch AVG, General Data Protection Regulation). Apart from the 
researchers of this team, inspectors of the national inspection of health (Inspectie 
Volksgezondheid) have access to the data.   
 
 
 

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10.2 Monitoring and Quality Assurance  
 
Research manager will be able to provide an audit of all activities in this study, and changes 
made in the CRF. A delegation log, is made and kept up to date. The sponsor/investigator 
will submit a summary of the progress of the trial to the accredited METC once a year. 
Information will be provided on the date of inclusion of the first subject, numbers of subjects 
included and numbers of subjects that have completed the trial, serious adverse events/ 
serious adverse reactions, other problems, and amendments. There is no need to provide a 
monitor plan in paragraph 7.4 is mentioned that in this study a DSMB is not needed, as the 
interventions consists of either care as usual, or a variation on care as usual. 
 
10.3 Amendments  
 
Amendments are changes made to the research after a favourable opinion by the 
accredited METC has been given. All amendments will be notified to the METC that gave 
a favourable opinion.  
 
All substantial amendments will be notified to the METC and to the competent authority. 
 
10.4 Annual progress report 
The sponsor/investigator will submit a summary of the progress of the trial to the 
accredited METC once a year. Information will be provided on the date of inclusion of the 
first subject, numbers of subjects included and numbers of subjects that have completed 
the trial, serious adverse events/ serious adverse reactions, other problems, and 
amendments.  
 
10.5 Temporary halt and (prematurely) end of study report 
The investigator/sponsor will notify the accredited METC of the end of the study within a 
period of 8 weeks. The end of the study is defined as the last patient’s last visit.  
 
The sponsor will notify the METC immediately of a temporary halt of the study, including 
the reason of such an action.  
    

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In case the study is ended prematurely, the sponsor will notify the accredited METC 
within 15 days, including the reasons for the premature termination. 
 
Within one year after the end of the study, the investigator/sponsor will submit a final 
study report with the results of the study, including any publications/abstracts of the study, 
to the accredited METC.  
 
10.6 Public disclosure and publication policy 
This trial is in the process of being pre-registered at ClinicalTrials.gov. The sponsor and 
investigator have agreed to full public disclosure of the research data and aim to publish 
the research data in a relevant journal, conform guidelines of the CCMO. 
  
11. Ethical considerations 
 
 11. 1 Benefits and risk assessment:  
Risks for patients participating in this study are minimal. This intervention has been 
successfully tested in a pilot study (Holmes et al., 2016), suggesting this intervention is 
able to decline mood variability in patients suffering from bipolar disorder, and also is well 
tolerated and well received by patients. The ImCT is offered without discontinuing care as 
usual (visits to the psychiatrist monitoring mood stabilizing medication). The same is the 
case for psychoeducation treatment. Psychoeducation treatment, although applied using a 
treatment protocol, is in line with psychological interventions offered routinely to BP 
patients. The extra burden for participants is the weekly questionnaires (20 minutes), and 
the questionnaires at T0-T4 (45 minutes), as daily monitoring is advised in current 
guidelines. 
Should patients relapse into mania or depression, they will receive standard care as 
usual. The benefits of participating in this study are also minimal. For participant in the 
ImCT condition, there might be the added benefit of having an intervention aimed at 
changing imagery, expected to form a central part of emotion amplification, but these 
effects above psychoeducation are not yet demonstrated. For participants in the 
psychoeducation condition the effects are not different from treatment as usual. It is 
important to note, they have the the possibility to receive ImCT after their participation to 
this study has ended. In the same line, the patients in the ImCT condition have the 
possibility to receive psychoeduation after this study has ended. 
 
 
 

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12 References: 
 
 
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