Condition category
Mental and Behavioural Disorders
Date applied
23/10/2017
Date assigned
25/10/2017
Last edited
30/10/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Autism Spectrum Conditions (ASCs) affect 2% of the population and are characterized by lifelong difficulties in social functioning with restricted patterns of behaviour and interests. People with ASCs are vulnerable to anxiety; at least 1 in 4 develops a co-morbid anxiety disorder, which may be resistant to typical drug therapy and psychological approaches. Interoception is the ability to sense internal changes in the body such as heart rate. Some of our recent work has shown anxiety can be increased if there is a discrepancy between how well patients feel they can interpret signals, such as their heartbeat, from their body and how well they are actually able to do this. It was found that helping people to be more aware of their ability, and to increase their ability to interpret signals from the body, helps reduce and may prevent anxiety symptoms. There is a need to try out and compare a new treatment, Aligning Dimensions of Interoceptive Experience (ADIE), teaching ASC patients these skills against the current treatment. The aim of this study is to test the efficacy of ADIE on anxiety symptoms and to check anxiety disorder diagnosis, medication and function one year later using state-of-the-art neuroimaging (images of the brain) to investigate the brain’s physiological response to ADIE, also guiding ways to optimise the therapy.

Who can participate?
Adults aged 18 and older who have a confirmed ASC diagnosis.

What does the study involve?
Participants are asked to fill out a set of questionnaires to ask about symptoms they might have (e.g. anxiety, depression) and about the way in which they experience emotion and signals from their body. Another questionnaire asks questions about interests and thought patterns. Participants are randomly allocated to one of two therapy groups, receiving either an existing therapy to improve recognition of emotion from the way people say things, called prosody, or the new ADIE therapy. They will then receive training according to the group they have been assigned to. Both types of therapy are accompanied by tasks which assess prosody (matching phrases to emotional faces or words), interoception (monitoring their own heartbeat), empathy (the ability to feel for others) and joint hypermobility (how bendy their joints are). Assessment sessions takes 1-2 hours, training sessions take around 30 minutes. There are three assessment sessions and six training sessions that areheld over the course of 3-4 weeks. At the end of the study participants are debriefed and asked about their experience and have the opportunity to ask any questions.

What are the possible benefits and risks of participating?
Participants may benefit from participating in the training as this may reduce or prevent any anxiety symptoms they may experience. This research could result in new ways of treating and preventing anxiety in people with autism spectrum conditions. There are no risks to taking part. Information from the study will be protected and anonymous so that people will not have access to the information about who took part or find out results of any one individual.

Where is the study run from?
Brighton and Sussex Medical School (UK)

When is the study starting and how long is it expected to run for?
January 2017 to December 2019

Who is funding the study?
MQ: Transforming Mental Health (UK)

Who is the main contact?
Professor Hugo Critchley
h.critchley@bsms.ac.uk

Trial website

https://www.mqmentalhealth.org/research/profiles/breaking-the-link-between-autism-and-anxiety

Contact information

Type

Scientific

Primary contact

Prof Hugo Critchley

ORCID ID

http://orcid.org/0000-0002-2445-9284

Contact details

Brighton & Sussex Medical School
University of Sussex
Falmer
Brighton
BN1 9RR
United Kingdom
+44 1273 873833
h.critchley@bsms.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

33694

Study information

Scientific title

Aligning Dimensions of Interoceptive Experience (ADIE) to prevent development of anxiety disorders in autism

Acronym

ADIE

Study hypothesis

After training to align dimensions of interoception in individuals with high-functioning autism, trait anxiety will be reduced and the development of anxiety disorders in autistic individuals will be prevented.

Ethics approval

Health Research Authority (HRA), 31/03/2017, ref: 17/WM/0125

Study design

Randomised; Interventional; Design type: Treatment, Prevention, Psychological & Behavioural

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

See additional files

Condition

Specialty: Mental Health, Primary sub-specialty: Developmental disorders - Autism; UKCRC code/ Disease: Mental Health/ Disorders of psychological development

Intervention

Participants are allocated to either the treatment or control arm using a 1:1 ratio and permuted block randomisation by the Clinical Trials Unit (CTU). After participant recruitment, the research assistant contacts the CTU to find out the allocation. To double-blind the clinical trial, neither the research assistant administering the treatment and control nor the participant are informed of which training regime is expected to deliver a therapeutic benefit.

The first of the three study phases is a double blind superiority randomised controlled trial comparing ADIE therapy to an active control therapy (prosody recognition training). Each group recruits 60 participants with ASCs (autism spectrum conditions).

Prosody therapy (Control group):
Participants receive an initial assessment where they are asked to complete some computer tasks. The computer tasks require application of finger sensors to measure their pulse. They receive three therapy sessions per week for three weeks. These focus on elements of speech such as intonation and rhythm. They are played phrases which are spoken in ways which convey different emotions (e.g. happy, sad, fearful etc.). The aim of this therapy is to help them better identify the emotion underlying the way in which things are said. They match phrases to different emotional faces and words, feedback is provided to help them improve their perception of emotion from the way people say things.

ADIE therapy (Active group):
Participants are asked to complete some computer tasks. The computer tasks require application of finger sensors to measure their pulse. They then receive three therapy sessions per week for three weeks. These focus on the participant’s ability to read signals from inside their body (what we call interoception) with feedback and guidance. They are asked to monitor their own heartbeat, but without physically feeling for it (i.e. just by sensing it internally). These tasks of interoception ask them to count how many heartbeats they feel during a period of time or decide if they think a rhythmic beep is in time or out of time with their own heartbeat. Participants are given feedback on how they have done in order to help them become more accurate in their awareness of their own heartbeats.

Participants undergo baseline (T0) testing of interoceptive abilities and affective (anxiety and depression) symptomatology, and are retested (after body awareness training and equivalent training in the active control group) and follow up after one year, to assess the impact of body-awareness training on potential reductions in anxiety, and indices of improved psychosocial functioning. A subset of ASC individuals from the ADIE therapy group undergo pre-post neuroimaging. Three week long therapist-guided training programme (three treatment sessions per week) focus on interoception with immediate feedback and guidance, in combination with established biofeedback techniques.

The effectiveness of ADIE therapy to a similar training protocol targeting ASC-relevant exteroceptive processing is compared, rather than using a sham feedback training control group (which we anticipate can enhance anxiety) or comparing the ADIE therapy group to a treatment-as-usual group.

Follow-up assessments are carried out by separate research assistant who was not involved in the delivery of the therapy.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Trait and state anxiety is measured using the STAI trait anxiety score State-Trait Anxiety Inventory determined from the STAI (State-Trait Anxiety Inventory questionnaire) at 3 months.

Secondary outcome measures

1. Anxiety is measured using the STAI state and trait anxiety scores at 1 year
2. Generalized anxiety is measured using the GAD7 score at three months and one year
3. Generalised anxiety is measured using the diagnosis criteria (MINI) met for generalized anxiety disorder at 1 year
4. Use of anxiolytic medication is measured using patient interviews at one year
5. Recovery is measured using the MINI criteria for anxiety disorder and the Spielberger trait anxiety score at three months and one year
6. Relapse is measured using the diagnostic criteria of the MINI generalised or social anxiety disorder with Spielberger trait anxiety score at one year
7. Trait Interoceptive prediction error on behavioural tests of interoceptive ability (error measured from z-score of heartbeat detection score accuracy -subjective (questionnaire and confidence) ratings of interoceptive 'sensibility' at 3 months and 1 year
8. Metacognitive interoceptive awareness measured from performance confidence correspondence (ROC curve analyses) at 3 months and 1 year
9. Clinical predictors of therapy response on ASD-related measures, i.e., cognitive, verbal and performance IQ, and ADI-R scores on dimensions of 1) social interaction, 2) communication and language and 3) repetitive stereotyped interests and behaviours predict magnitude of change in Spielberger anxiety score at 3 months and 1 year
10. Functional neural datasets is measured using SPM (Statistical Parametric Mapping) at 3 months and their relation to symptom response to treatment
11. Established efficacy of implementable software solution (beta testing–comparison against laboratory training methods therapist-measured ratings of ease-of-use) at 1 year
12. Participant’s capacity to control the occurrence of mindwandering and contents of their experience is measured using a 0-back-1-back-task and MDES (Multi-Dimensional Experience Sampling) at 3 months and 1 year

Overall trial start date

01/01/2017

Overall trial end date

31/12/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. ADI-R confirmed ASC diagnosis
2. Aged 18 and over
3. Normal or corrected-to-normal vision
4. Fluent English speakers

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 120; UK Sample Size: 120

Participant exclusion criteria

1. Age below 18 years
2. Past head injury or neurological disorders
3. History of major medical or psychiatric disorder (other than anxiety and co-morbid depression)
4. Cognitive impairment
5. History of substance or alcohol dependence
6. Heart disease
7. Obesity (body mass index > 30kg/m2)
8. Hypertension (>140/90 mm Hg)
9. Pregnancy
10. Asthma/respiratory illness
11. Migraines
12. Claustrophobia or other MRI exclusions
13. Upper age limit of 65

Recruitment start date

01/11/2017

Recruitment end date

01/08/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Brighton and Sussex Medical School
University of Sussex Trafford Centre Falmer
Brighton
BN1 9RR
United Kingdom

Sponsor information

Organisation

Sussex Partnership NHS Foundation Trust

Sponsor details

Assessment and Treatment Centre
Chapel Street
Chicester
West Sussex
Arundel Road
Worthing
PO19 1BX
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

MQ: Transforming Mental Health

Alternative name(s)

MQ

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Research findings will be presented at conferences and in publications. The aim is to submit findings for publication within 6 months of data acquisition. All publications will be open access.
Findings will be to presented back to patients, at local Mood and Anxiety research Sussex (MARS) engagement events, at Sussex Partnership Trust Research and Developmental annual conference and to local third sector organisation meeting ASSERT Brighton and Hove.
Target journals for publication are British Journal of Psychiatry, Biological Psychiatry, and Brain. Another target is publication in a practice-based journal to broaden awareness of ADIE therapy if the trial is successful (e.g. Journal of Consulting and Clinical Psychology; Behaviour Therapy and Journal of Engagement and Involvement).
Within the technology development part of the project a market analyses and pathways to introduce into practice will be defined if the approach is established to be effective. There is planning for an Impact event for year 3 to launch this application to the healthcare sector.
The findings shall be disseminated at three to four key scientific conferences: International Congress of the Royal College of Psychiatrists in year 1; European Congress (EPA) year 2; Biological Psychiatry and or Social for Neurosciences (USA) Year 3.

IPD sharing statement:
The datasets generated during and/or analysed during the current study will be stored in a non-publically available repository Health, physiological, medical and performance data will be obtained from participants in the research and stored for the purposes of analysis and recording. During informed consent, all participants will be made aware of the methods used for handling personal data, the justification for requesting/obtaining their data, the duration of data use and storage and the guarantees concerning the rightful use of data. The basic principle regarding data storage throughout this project is that data will be anonymised (removal of all personal identifiers and held for a minimum of 5 years from the time of collection). The research team and the Institute abide by the Data Protection Act (1998) and will ensure all research is conducted according to EU legislation and the forthcoming EU Regulation on Data Protection. Data will be held on password protected computers or locked filing cabinets within university premises. Participant identifiers will be removed from all databases, and anonymised data will be used in all cases of dissemination. A copy of the participant identifier key will be stored in hard copy from within a single locked filing cabinet accessible by the PI, lead Co-I and CTU manager. An electronic record of this anonymisation key will be stored in encrypted password protected form on the Co-I’s computer. The participant’s identifier numbers will be used for all written forms, scanning data and physiological recording files. Data storage will conform to EU data protection legislation within firewalled, virus screened hardware on University of NHS premises. The length of storage will in part be determined by the nature of data; the National Research Ethics Service (NRES) advise long term storage of neuroimaging data.

Intention to publish date

31/12/2020

Participant level data

Stored in repository

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

30/10/2017: Please note that all genders are accepted to participate in this study.