Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000998842
Ethics application status
Approved
Date submitted
25/05/2021
Date registered
29/07/2021
Date last updated
30/09/2022
Date data sharing statement initially provided
29/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Nocebo Hypothesis Cognitive Behavioural Therapy (NH-CBT) for non-epileptic seizures
Scientific title
Nocebo Hypothesis Cognitive Behavioural Therapy (NH-CBT) for non-epileptic seizures: a consecutive case series.
Secondary ID [1] 304306 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non epileptic seizures 322047 0
Condition category
Condition code
Neurological 319772 319772 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
As the delivery of a non-epileptic seizure (NES) diagnosis has been demonstrated to lead to full remission of seizures in a substantial minority of people with NES in previous studies (e.g. 14%), participants will be informed of this, and told to contact the lead investigator only if they experience further any seizure activity post-diagnosis delivery.

If they do contact the lead investigator, eligible participants will then undergo baseline assessment by an independent assessor (research assistant), and asked to start a seizure diary (the format of this will be negotiated with the lead investigator on an individual basis, i.e. paper vs text or phone reporting).

As soon as is pragmatically possible after this baseline assessment, they will then receive the first session of Nocebo-Hypothesis Cognitive Behavioural Therapy (NH-CBT) for NES. All therapeutic intervention throughout the study will be delivered by the lead investigator, a clinical psychologist with 26 years clinical experience. This will involve around 90 minutes of psychological assessment, education and treatment (dependent on the participant’s existing knowledge) including the following components: gathering information about participants’ medical history, the onset and course of the seizures, the participant’s understanding of the medical evidence, their personal belief about the causes of their symptoms, and their understanding of the terms ‘subconscious’ and ‘placebo effect’. A psychological formulation is then shared with the participant that incorporates relevant history within a hypothesis that the seizures are caused by a nocebo effect. The aim is to engender in the participant an alternative belief about their symptoms, to challenge the one currently held (e.g. “the doctors have missed something”, “there’s something wrong with my brain”).

The treatment will then be paused, and only continued if / when the participant experiences another seizure.

The next session will start by assessing the participants’ belief in the “nocebo hypothesis” versus their belief in their originally held view (usually that they have a neurological condition, e.g. epilepsy). If the originally held view is still considered more likely than the “nocebo hypothesis”, then evidence for and against this is discussed. Once the nocebo hypothesis is seen as at least equally more likely than any other cause by the participant, a graded exposure hierarchy is made in collaboration with the participant, where antecedents that the person believes could trigger their seizures are subjectively ranked from ‘most likely’ to ‘least likely’. The person then gradually exposes themselves to those triggers (starting with least likely), having previously been taught some techniques that may help prevent seizures (e.g. distraction, grounding). The lack of subsequent seizure is discussed as further evidence that they do not have epilepsy, that the perceived trigger is not harmful, and that perhaps a subconscious belief was indeed responsible for previous seizures.
Throughout treatment, the therapist will intentionally portray as much optimism as possible to the participant about potential recovery, e.g. talking about how many people have got rid of their seizures using NH-CBT.
Participants will receive therapy over a period of up to 12 weeks, with the frequency of therapy being guided by the frequency of the seizures (e.g. if the seizure frequency is severe enough to warrant inpatient treatment, then therapy may take place for approximately two hours a day). Total time spent in therapy sessions will be monitored. Therapy will cease when the participant has no perceived triggers that they have not been repeatedly exposed to. If therapy ceases early, and there is a recurrent seizure before the 12 week treatment period is complete, then therapy will reconvene, exposing the person to whatever preceded that most recent seizure, in a graduated fashion whenever possible.
Participants will also receive written information about their diagnosis and treatment, outlining the “nocebo hypothesis” regarding non-epileptic seizures, including information about the concept of subconscious processing and the placebo/nocebo effect. There will also be clear description of the treatment.
Treatment will predominantly take place at the ISIS Rehabilitation Centre, Wakari Hospital, Dunedin, although there may sometimes be some home and community-based intervention, depending on the participant's perceived triggers.

Intervention code [1] 320649 0
Rehabilitation
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327632 0
Seizure frequency, as measured by a seizure diary.
Timepoint [1] 327632 0
0 weeks (baseline; likely to be retrospective), 12 weeks (post-treatment) and 6 months after post-treatment timepoint.
Secondary outcome [1] 396009 0
Patient perception of change, as measured by the Clinical Global Impression Scale of Improvement (CGI-I)
Timepoint [1] 396009 0
12 weeks after baseline (post-treatment) and 6 months after post-treatment timepoint.
Secondary outcome [2] 396011 0
Somatic symptom severity, as measured by the Patient Health Questionnaire-15 (PHQ-15)
Timepoint [2] 396011 0
0 weeks (baseline), 12 weeks (post-treatment) and 6 months after post-treatment timepoint.
Secondary outcome [3] 396012 0
Health care utilisation, as measured by Hospital and GP data, collected in the format of Q.7 and 8 of the Client Service Receipt Inventory (CSRI) for self-report, and using computerised health records for objective verification.
Timepoint [3] 396012 0
0 weeks (baseline) and 6 months after post-treatment timepoint.
Secondary outcome [4] 396014 0
Illness Perception, as measured by the Brief Illness Perception Questionnaire (B-IPQ)
Timepoint [4] 396014 0
0 weeks (baseline), 12 weeks (post-treatment) and 6 months after post-treatment timepoint.
Secondary outcome [5] 396015 0
Health-related quality of life, as measured by the Short Form 36 (SF36)
Timepoint [5] 396015 0
0 weeks (baseline), 12 weeks (post-treatment) and 6 months after post-treatment timepoint.
Secondary outcome [6] 396016 0
Health economics, to generate QALYS, as measured by the EQ-5D-5L
Timepoint [6] 396016 0
0 weeks (baseline), 12 weeks (post-treatment) and 6 months after post-treatment timepoint.
Secondary outcome [7] 396017 0
Fatigue, as measured by the Vitality Scale of the Short Form 36 (SF36).
Timepoint [7] 396017 0
0 weeks (baseline), 12 weeks (post-treatment) and 6 months after post-treatment timepoint.
Secondary outcome [8] 396018 0
Catastrophic thinking about symptoms, as measured by the Symptom Catastophising Scale.
Timepoint [8] 396018 0
0 weeks (baseline), 12 weeks (post-treatment) and 6 months after post-treatment timepoint.
Secondary outcome [9] 396019 0
Anxiety, as measured by the Generalised Anxiety Disorder scale (GAD-7).
Timepoint [9] 396019 0
0 weeks (baseline), 12 weeks (post-treatment) and 6 months after post-treatment timepoint.
Secondary outcome [10] 396020 0
Depression, as measured by the Patient Health Questionnaire-9 (PHQ-9).
Timepoint [10] 396020 0
0 weeks (baseline), 12 weeks (post-treatment) and 6 months after post-treatment timepoint.
Secondary outcome [11] 396021 0
Dissociation, as measured by the Brief Dissociative Experiences Scale (DES-B).
Timepoint [11] 396021 0
0 weeks (baseline), 12 weeks (post-treatment) and 6 months after post-treatment timepoint.
Secondary outcome [12] 396022 0
Symptom disability, as measured by the Pain Disability Index (modified).
Timepoint [12] 396022 0
0 weeks (baseline), 12 weeks (post-treatment) and 6 months after post-treatment timepoint..
Secondary outcome [13] 396023 0
Therapeutic alliance, as measured by the Work Alliance Inventory – Short Form (modified version).
Timepoint [13] 396023 0
12 weeks post-baseline (post-treatment).
Secondary outcome [14] 396024 0
Adverse events in therapy, as measured by the Inventory for the balanced assessment of Negative Effects of Psychotherapy (INEP), and the Severity Assessment Code (SAC) rating for adverse event reporting.
Timepoint [14] 396024 0
12 weeks post-baseline (post-treatment)

Eligibility
Key inclusion criteria
Participants that will be included in our trial will have to meet the following criteria:
• have been assessed by a neurologist including the appropriate medical investigation, and that assessment will have resulted in that neurologist identifying that the participant has had a non-epileptic seizure in the last 8 weeks.
• have consented to participate, and report every seizure experienced.
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be excluded from the trial if they meet the following criteria:
• they have a diagnosis of Dissociative Identity Disorder (DID)
• they have a diagnosis of Post-Traumatic Stress Disorder (PTSD) with high severity and significant dissociation.
• they meet diagnostic criteria for current alcohol/drug dependence.
• they require inpatient mental health treatment during the trial.
• they receive psychopharmacotherapy and change their treatment regimen at any time between baseline assessment and post-therapy assessment.
• according to the clinical judgement of the lead investigator, there are concerns about their ability to participate fully in the trial, e.g. they have active and extensive self-harm, or frequent admissions for inpatient mental health treatment in the last two months.
• their English language proficiency is low.
• they do not have the capacity to consent to participating in the trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Consecutive case series.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive statistics only will be used to summarise the results, such as means, percentages and ranges, with reference to normative data where possible. Individual case data will also be reported with respect to seizure frequency across the weeks of the treatment period.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
30/07/2021
Actual
5/10/2021
Date of last participant enrolment
Anticipated
28/02/2022
Actual
19/04/2022
Date of last data collection
Anticipated
9/02/2023
Actual
Sample size
Target
10
Accrual to date
Final
10
Recruitment outside Australia
Country [1] 23720 0
New Zealand
State/province [1] 23720 0
Otago

Funding & Sponsors
Funding source category [1] 308681 0
University
Name [1] 308681 0
University of Otago
Country [1] 308681 0
New Zealand
Primary sponsor type
Individual
Name
Dr Matt Richardson
Address
Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 309561 0
Individual
Name [1] 309561 0
Dr Maria Kleinstaeuber
Address [1] 309561 0
Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country [1] 309561 0
New Zealand
Secondary sponsor category [2] 309565 0
Individual
Name [2] 309565 0
Professor Paul Glue
Address [2] 309565 0
Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country [2] 309565 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308603 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 308603 0
Ethics committee country [1] 308603 0
New Zealand
Date submitted for ethics approval [1] 308603 0
27/05/2021
Approval date [1] 308603 0
11/06/2021
Ethics approval number [1] 308603 0
21/NTB/146

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 111294 0
Dr Matt Richardson
Address 111294 0
Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country 111294 0
New Zealand
Phone 111294 0
+64 274585634
Fax 111294 0
Email 111294 0
[email protected]
Contact person for public queries
Name 111295 0
Matt Richardson
Address 111295 0
Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country 111295 0
New Zealand
Phone 111295 0
+64 274585634
Fax 111295 0
Email 111295 0
[email protected]
Contact person for scientific queries
Name 111296 0
Matt Richardson
Address 111296 0
Department of Psychological Medicine
Dunedin School of Medicine
University of Otago
PO Box 56
Dunedin 9054
Country 111296 0
New Zealand
Phone 111296 0
+64 274585634
Fax 111296 0
Email 111296 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie the results reported in this record, after de-identification (text, tables, figures, and appendices).
When will data be available (start and end dates)?
Immediately following publication; no end date.
Available to whom?
Researchers who provide a methodologically sound proposal for re-analyses.
Available for what types of analyses?
For re-analyses, if their aim is covered by the purpose described and agreed on in the patient information sheet and informed consent.
How or where can data be obtained?
Proposals should be directed to the Principal Investigator ([email protected]). To gain access, data requestors will need to sign a data access agreement. Data are not publicly available because informed consent provided by participants of this study is committed to a defined purpose.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
11756Study protocol  [email protected]



Results publications and other study-related documents

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