Generalised Anxiety DisorderNCT05549102
CBT and the Neural Circuits of Anxiety
An observational study of Generalised Anxiety Disorder and Anxiety Disorders, run by UCLH/UCL Joint Research Office at 1 site in United Kingdom.
Trial summary
This study will aim to test whether specific neural circuitry changes, proposed on the basis of a neurocognitive model of anxiety, are a mechanism of action for Cognitive Behavioural Therapy (CBT) interventions. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Generalised Anxiety Disorder, Anxiety Disorders, CBT
- What is being tested?
- Cognitive Behavioural Therapy and Waiting List
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 174 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 2 Feb 2020to 1 Dec 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- Adult
Study population: Individuals entering IAPT services (IAPT step 3; i.e., full CBT) for anxiety disorders
Who may be able to join
- Enrolled in IAPT Step 3 (high intensity service)
- Score of or above 8 on the GAD-7 (indicating moderate anxiety on a standard scale of anxiety; Spitzer et al., 2006)
- Willing and able to provide written consent
Who cannot join
- Score above 22 on the GAD-7
- Past/present psychotic disorder, bipolar disorder/mania or alcohol/substance use disorder (outside a comorbid psychiatric episode)
- History of medical illness that may impair cognitive function (e.g. serious head injury, endocrine disorder)
- Current psychotropic pharmacological intervention (e.g. SSRIs) or use within 3 months
- MRI contraindications such as pacemaker, aneurysm clip, cochlear implant, neurostimulator, IUD, shrapnel, metal fragments in eye, weight of above 250lbs or claustrophobia
- Females who are pregnant, planning pregnancy, or breastfeeding
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Institute of Cognitive Neuroscience, University College London
London, WC1N 3AZ
Oliver J Robinson, PhD, 020 7679 1150, o.robinson@ucl.ac.uk
Oliver J Robinson, PhD
About this study
Official title: The Impact of CBT on Shock-Potentiated Neural Circuity
This study will aim to test whether specific neural circuitry changes, proposed on the basis of a neurocognitive model of anxiety, are a mechanism of action for Cognitive Behavioural Therapy (CBT) interventions. This study aims to provide a theoretical model of the neurobiological mechanisms of CBT's therapeutic effect, where there currently is none, and potentially allow for more targeted/specific approaches to anxiety disorders following the identification of key CBT mechanisms. The ultimate aim is to improve the efficacy of CBT, and more generally, psychological interventions for anxiety disorders.
Read the detailed description
To test the hypothesis that the neural circuitry of the amygdala and prefrontal cortex will respond to CBT, the impact of a course of CBT on cortical-subcortical circuitry will be tested via a case-control study in individuals entering Improving Access to Psychological Therapies (IAPT) services (IAPT step 3; i.e., full CBT) for anxiety disorders and individuals in waiting lists. This design leverages the naturalistic waiting times in the clinical service and does not interfere with treatment as usual. Measures of brain region-specific connectivity and emotion-related behavioural performance will be assessed through testing sessions at the University College London (UCL) Institute of Cognitive Neuroscience and the Birkbeck-UCL Centre for NeuroImaging (BUCNI), involving computerised cognitive/psychological tasks and functional magnetic resonance imaging (fMRI).
The aims are to:
- test whether this circuit responds to a course of CBT, by demonstrating disengagement of the circuit following CBT
- relate this change in circuit function to behaviour through cognitive measures of emotional processing
- explore the neurobiological features that distinguish patients who respond to CBT and those who do not
- compare the data from this study to another on-going study assessing the impact of pharmacological interventions for anxiety, allowing for the comparison of neurobiological mechanisms of psychological vs. pharmacological treatments in anxiety.
- Conditions
- Generalised Anxiety Disorder, Anxiety Disorders, CBT, Anxiety Depression, Anxiety Disorders and Symptoms, Anxiety Generalized
- Being tested
- Cognitive Behavioural Therapy, Waiting List
- Keywords
- GAD, generalised anxiety disorder, anxiety disorders, cognitive behavioural therapy, CBT, psychological therapy, neural circuitry, emotional processing
- Medical subject headings
- Generalized Anxiety Disorder, Anxiety Disorders, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive Behavioural TherapyBehavioural
Also called CBT
In the Cognitive Behavioural Therapy group (N=87), patients will undergo CBT as part of their routine care in Step 3 of the IAPT programme. This will be administered by suitably trained clinicians. The specification of CBT is as recommended by the National Institute for Health and Care Excellence (NICE) guidelines (CG113 - Generalised anxiety disorder and panic disorder in adults: management). In these guidelines, patients are offered on average, 12-15 hourly, weekly sessions of CBT with a trained and competent practitioners. Therapy sessions involve discussions that identify patterns in thinking or behaviours which may be problematic, and therapists and patients work to set goals to reduce these using cognitive techniques. The principle is to teach the patient how to use CBT techniques in their day-to-day life to promote a lasting effect on mental health. We will test patients before (T1) and after (T2) a course of treatment.
Waiting ListOther
In the control group (N=87), we will test patients who are currently seeking (but not undergoing) treatment before (T1) and after a wait (T2) of equivalent time (i.e. waiting list controls)
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group | Participants undergoing a course of Cognitive Behavioural Therapy (CBT) Receives: Behavioral: Cognitive Behavioural Therapy | |
| Waiting List Group | Participants on the Waiting List for CBT Receives: Other: Waiting List |
What is being measured
The primary outcome is the main question the study is designed to answer.
'Aversive amplification circuit' connectivity
The engagement of the neural circuit of the amygdala, cingulate cortex and prefrontal cortex will be measured via an fMRI analysis technique called a psychophysiological interactions (PPI) analysis. PPI analysis concerns behaviour-specific increases in the relationship across regional brain activity - this means that it can allow one to assess whether two regions (a priori selected ROIs) show increased connectivity during a specific context or behaviour, suggesting a behaviour-specific increase in transfer of information. The output of this analysis will take form of a continuous beta weight - an index of connectivity across two brain regions (amygdala and medial prefrontal cortex), which represents the primary outcome of the study.
Measured: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary outcomes (16)
Cognitive task performance: Loss/risk aversion task
Measures how averse participants are to risk and loss in a mock gambling context
Measured: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Cognitive task performance: Go/no-go task
Measures approach/avoidance behaviours under threat of shock or safe conditions
Measured: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Cognitive task performance: Facial emotional processing task
Measures brain responses to positive, negative and neutral emotions
Measured: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Cognitive task performance: Emotional face recognition task
Measures brain responses during two distinct memory processes - the encoding (learning) and retrieval (remembering) of information
Measured: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Cognitive task performance: Visual affective bias task
Measures biases in patients' cognition towards or away from rewarding stimuli
Measured: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Regional activations during neuroimaging task: Facial emotional processing task
Measures brain responses to positive, negative and neutral emotions
Measured: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Regional activations during neuroimaging task: Emotional face recognition task
Measures brain responses during two distinct memory processes - the encoding (learning) and retrieval (remembering) of information
Measured: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Regional activations during neuroimaging task: Visual affective bias task
Measures biases in patients' cognition towards or away from rewarding stimuli
Measured: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measure: Generalised Anxiety Disorder Scale (GAD-7)
Measures symptoms of generalised anxiety, scored between 0-21 with higher scores indicating more severe symptoms
Measured: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measure: State Trait Anxiety Inventory (STAI)
Measures state and trait anxiety symptoms, scored between 20-80 with higher scores indicating more severe symptoms
Measured: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measures: Patient Health Questionnaire (PHQ-9)
Measures depressive symptoms, scored between 0-27 with higher scores indicating more severe symptoms
Measured: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measures: Beck's Depression Inventory (BDI)
Measures depressive symptoms, scored between 0-63 with higher scores indicating more severe symptoms
Measured: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measures: Catastrophizing questionnaire
Measures catastrophising, scored between 24-120 with higher scores indicating more severe symptoms
Measured: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measures: Daily Stress Inventory (DSI)
Measures frequency and impact of daily stresses. Frequency scored between 0-58 and impact scored between 0-6, with higher scores indicating more severe stress
Measured: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measures: Behavioural Inhibition/Behavioural Activation Scales (BIS/BAS)
Measures drive, fun-seeking, reward responsiveness and behavioural inhibition. Behavioural inhibition scored between 7-28, drive between 4-16, fun seeking between 4-16, and reward between 5-20, with higher scores indicating higher levels of those behaviours
Measured: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measures: Eysenck Impulsiveness Scale
Measures impulsiveness, venturesomeness and empathy. Impulsivity scored between 0-19, venturesomeness between 0-16, empathy between 0-18, with higher scores indicating higher levels of those traits
Measured: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2022
- Study start2 Feb 2020
- Primary completion1 Dec 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Generalised Anxiety DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 174 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UCLH/UCL Joint Research Office
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council, Camden and Islington NHS Trust, Central and North West London NHS Foundation Trust
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05549102
- Sponsor's protocol ID
- 121261
- Other IDs
- 255501
- Status last verified
- Jun 2025
- First submitted
- 7 Sep 2022
- Last updated
- 29 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The data may also be published as open-access data online. In this case, all personally-identifiable data will be removed such that participants cannot be identified from this open data.
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of CBT on Shock-Potentiated Neural Circuity
- ClinicalTrials.gov ID
- NCT05549102
- Acronym / sponsor ID
- 121261
- Conditions
- Generalised Anxiety Disorder, Anxiety Disorders, CBT, Anxiety Depression, Anxiety Disorders and Symptoms, Anxiety Generalized
- Keywords
- GAD, generalised anxiety disorder, anxiety disorders, cognitive behavioural therapy, CBT, psychological therapy, neural circuitry, emotional processing
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 174 participants (estimated)
- Lead sponsor
- UCLH/UCL Joint Research OfficeUniversity, hospital or other
- Collaborators
- Medical Research Council, Camden and Islington NHS Trust, Central and North West London NHS Foundation Trust
- Study start
- 2 Feb 2020 (actual)
- Primary completion
- 1 Dec 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 22 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will aim to test whether specific neural circuitry changes, proposed on the basis of a neurocognitive model of anxiety, are a mechanism of action for Cognitive Behavioural Therapy (CBT) interventions. This study aims to provide a theoretical model of the neurobiological mechanisms of CBT's therapeutic effect, where there currently is none, and potentially allow for more targeted/specific approaches to anxiety disorders following the identification of key CBT mechanisms. The ultimate aim is to improve the efficacy of CBT, and more generally, psychological interventions for anxiety disorders.
Detailed description
To test the hypothesis that the neural circuitry of the amygdala and prefrontal cortex will respond to CBT, the impact of a course of CBT on cortical-subcortical circuitry will be tested via a case-control study in individuals entering Improving Access to Psychological Therapies (IAPT) services (IAPT step 3; i.e., full CBT) for anxiety disorders and individuals in waiting lists. This design leverages the naturalistic waiting times in the clinical service and does not interfere with treatment as usual. Measures of brain region-specific connectivity and emotion-related behavioural performance will be assessed through testing sessions at the University College London (UCL) Institute of Cognitive Neuroscience and the Birkbeck-UCL Centre for NeuroImaging (BUCNI), involving computerised cognitive/psychological tasks and functional magnetic resonance imaging (fMRI).
The aims are to:
- test whether this circuit responds to a course of CBT, by demonstrating disengagement of the circuit following CBT
- relate this change in circuit function to behaviour through cognitive measures of emotional processing
- explore the neurobiological features that distinguish patients who respond to CBT and those who do not
- compare the data from this study to another on-going study assessing the impact of pharmacological interventions for anxiety, allowing for the comparison of neurobiological mechanisms of psychological vs. pharmacological treatments in anxiety.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Group | – | Behavioral: Cognitive Behavioural TherapyParticipants undergoing a course of Cognitive Behavioural Therapy (CBT) |
| Waiting List Group | – | Other: Waiting ListParticipants on the Waiting List for CBT |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Age groups
- Adult
- Study population
- Individuals entering IAPT services (IAPT step 3; i.e., full CBT) for anxiety disorders
Key inclusion criteria (3 listed)
- Enrolled in IAPT Step 3 (high intensity service)
- Score of or above 8 on the GAD-7 (indicating moderate anxiety on a standard scale of anxiety; Spitzer et al., 2006)
- Willing and able to provide written consent
Key exclusion criteria (6 listed)
- Score above 22 on the GAD-7
- Past/present psychotic disorder, bipolar disorder/mania or alcohol/substance use disorder (outside a comorbid psychiatric episode)
- History of medical illness that may impair cognitive function (e.g. serious head injury, endocrine disorder)
- Current psychotropic pharmacological intervention (e.g. SSRIs) or use within 3 months
- MRI contraindications such as pacemaker, aneurysm clip, cochlear implant, neurostimulator, IUD, shrapnel, metal fragments in eye, weight of above 250lbs or claustrophobia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive Behavioural TherapyAlso: CBTIn the Cognitive Behavioural Therapy group (N=87), patients will undergo CBT as part of their routine care in Step 3 of the IAPT programme. This will be administered by suitably trained clinicians. The specification of CBT is as recommended by the National Institute for Health and Care Excellence (NICE) guidelines (CG113 - Generalised anxiety disorder and panic disorder in adults: management). In these guidelines, patients are offered on average, 12-15 hourly, weekly sessions of CBT with a trained and competent practitioners. Therapy sessions involve discussions that identify patterns in thinking or behaviours which may be problematic, and therapists and patients work to set goals to reduce these using cognitive techniques. The principle is to teach the patient how to use CBT techniques in their day-to-day life to promote a lasting effect on mental health. We will test patients before (T1) and after (T2) a course of treatment. | Behavioural | Treatment Group |
| Waiting ListIn the control group (N=87), we will test patients who are currently seeking (but not undergoing) treatment before (T1) and after a wait (T2) of equivalent time (i.e. waiting list controls) | Other | Waiting List Group |
Primary outcome
'Aversive amplification circuit' connectivity
Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
The engagement of the neural circuit of the amygdala, cingulate cortex and prefrontal cortex will be measured via an fMRI analysis technique called a psychophysiological interactions (PPI) analysis. PPI analysis concerns behaviour-specific increases in the relationship across regional brain activity - this means that it can allow one to assess whether two regions (a priori selected ROIs) show increased connectivity during a specific context or behaviour, suggesting a behaviour-specific increase in transfer of information. The output of this analysis will take form of a continuous beta weight - an index of connectivity across two brain regions (amygdala and medial prefrontal cortex), which represents the primary outcome of the study.
16 secondary outcomes
Cognitive task performance: Loss/risk aversion task
Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Cognitive task performance: Go/no-go task
Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Cognitive task performance: Facial emotional processing task
Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Cognitive task performance: Emotional face recognition task
Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Cognitive task performance: Visual affective bias task
Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Regional activations during neuroimaging task: Facial emotional processing task
Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Regional activations during neuroimaging task: Emotional face recognition task
Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Regional activations during neuroimaging task: Visual affective bias task
Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measure: Generalised Anxiety Disorder Scale (GAD-7)
Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measure: State Trait Anxiety Inventory (STAI)
Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measures: Patient Health Questionnaire (PHQ-9)
Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measures: Beck's Depression Inventory (BDI)
Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measures: Catastrophizing questionnaire
Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measures: Daily Stress Inventory (DSI)
Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measures: Behavioural Inhibition/Behavioural Activation Scales (BIS/BAS)
Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Clinical symptom measures: Eysenck Impulsiveness Scale
Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2025.
- Individual participant dataSharing planned: Undecided. The data may also be published as open-access data online. In this case, all personally-identifiable data will be removed such that participants cannot be identified from this open data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Generalised Anxiety Disorder and Anxiety Disorders, run by UCLH/UCL Joint Research Office at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Emily Lewis (02039872331, emily.lewis.23@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
'Aversive amplification circuit' connectivity (time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2025.