Evaluating the efficacy of an AI-delivered, neurosymbolic, human-supervised digital intervention for depression and anxiety versus standard cognitive-behavioural therapy in young persons and adults
| ISRCTN | ISRCTN15357676 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15357676 |
| Integrated Research Application System (IRAS) | 369133 |
| Sponsor | PsyScale Ltd |
| Funder | PsyScale Ltd |
- Submission date
- 29/04/2026
- Registration date
- 06/05/2026
- Last edited
- 05/05/2026
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Mental and Behavioural Disorders
Plain English summary of protocol
Background and study aims
Depression and anxiety are common mental health conditions that can significantly affect daily life. Cognitive-behavioural therapy (CBT) is an effective treatment, but many people face long waiting times to access it. Nook is an AI-enabled digital programme developed by PsyScale that delivers structured psychological support based on CBT and ACT (Acceptance and Commitment Therapy) through a conversational interface. This study aims to find out whether Nook works as well as standard remote CBT for reducing symptoms of depression and anxiety.
Who can participate?
Adults and young people aged 16-64 years who have moderate to moderately-severe symptoms of depression and/or moderate to severe anxiety symptoms, sufficient English language skills, and access to an internet-connected device. Participants must not have severe depressive symptoms or high clinical risk.
What does the study involve?
Participants will be randomly assigned to either use Nook for 6-10 weeks or receive standard remote CBT. They will complete questionnaires about their symptoms at several points during the study. There are no invasive tests or biological samples required.
What are the possible benefits and risks of participating?
By taking part, participants will be helping to find out what works best for people with anxiety and depression. If Nook is shown to work as well as regular therapy, it could help many people access support faster. As with any therapy, some participants may experience difficult feelings, frustration, or feel worse before feeling better. Additional minor risks include questionnaire burden, fatigue, and difficulty concentrating. There is a small chance Nook could produce an unexpected response, though qualified clinicians monitor the system at all times.
Where is the study run from?
PsyScale Ltd. (UK)
When is the study starting and how long is it expected to run for?
June 2026 to January 2027.
Who is funding the study?
PsyScale Ltd. (UK)
Who is the main contact?
The main contact for this study is Stephanie Argue from, Senior Project Lead at Lindus Health, stephanie.argue@lindushealth.com
Contact information
Public
Lindus Health - 65 Southwark Street
London
SE1 0HR
United Kingdom
| Phone | +44 808 258 7706 |
|---|---|
| stephanie.argue@lindushealth.com |
Scientific
86-90 Paul Street
London
EC2A 4NE
United Kingdom
 ORCID ID |
0000-0003-0511-5432 |
|---|---|
| Phone | +44 7902 241486 |
| marcos.economides.ext@psyscale.ai |
Principal investigator
Lindus Health - 65 Southwark Street
London
SE1 0HR
United Kingdom
| ORCID ID |
0009-0001-9137-9727 |
|---|---|
| Phone | +44 7367 142663 |
| luke@lindushealth.com |
Study information
| Primary study design | Interventional |
|---|---|
| Allocation | Randomized controlled trial |
| Masking | Open (masking not used) |
| Control | Active |
| Assignment | Parallel |
| Purpose | Treatment |
| Scientific title | Evaluating the efficacy of an AI-delivered, neurosymbolic, human-supervised digital intervention for depression and anxiety versus standard cognitive-behavioural therapy in young persons and adults: a pivotal, randomised, controlled, non-inferiority trial |
| Study objectives | To determine whether Nook is non-inferior to standard CBT-based talking therapy in reducing symptoms of depression and/or anxiety at 9 weeks post-randomisation. |
| Ethics approval(s) |
Submitted 28/04/2026, South Birmingham REC (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 207 104 8107; southbirmingham.rec@hra.nhs.uk), ref: 26/WM/0050 |
| Health condition(s) or problem(s) studied | Depression and anxiety (Generalised Anxiety Disorder and/or Major Depressive Disorder) |
| Intervention | Arm 1 – Nook (Investigational Device): Participants will receive access to Nook, a clinician-supervised, AI-enabled digital psychological intervention developed by PsyScale. Nook delivers structured, evidence-based psychological content derived from Cognitive Behavioural Therapy (CBT) and Acceptance and Commitment Therapy (ACT) via an interactive, text-based conversational interface, supplemented by guided exercises and audio components. The programme consists of four core therapeutic modules (Values and Behavioural Activation, Cognitive Defusion, Sleep and Circadian Regulation, and Graded Exposure), delivered in a fixed sequence, followed by a consolidation and relapse-prevention module. Typical intervention duration is 6–10 weeks, with sessions approximately two times per week and an average session length of 20–25 minutes. Nook is delivered via mobile app, web browser, or tablet under ongoing clinician supervision. Arm 2 – Standard CBT (Control): Participants will receive standard cognitive-behavioural therapy delivered remotely by a qualified therapist for 9 consecutive weeks, representing the current standard of care for depression and/or anxiety. Both arms will be compared on clinical outcomes to assess the non-inferiority of Nook relative to standard CBT. Participants will be randomised in a 1:1 ratio and is stratified by age (16-17, 18-21, 22-64) to ensure balanced allocation across clinically and regulatorily meaningful developmental groups. |
| Intervention type | Device |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | NOOK |
| Primary outcome measure(s) |
|
| Key secondary outcome measure(s) |
|
| Completion date | 27/01/2027 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Mixed |
| Lower age limit | 16 Years |
| Upper age limit | 64 Years |
| Sex | All |
| Target sample size at registration | 400 |
| Key inclusion criteria | 1. Have symptoms of generalised anxiety disorder and or symptoms of major depressive disorder as the primary reason for seeking treatment as determined by a psychological well-being practitioner 1.1. Symptoms may meet criteria for either or both disorders 2. Meet symptom severity criteria on either validated screening measure 2.1. Depression assessed using PHQ-9 or PHQ-A for young people with a total score between 10 and 19 corresponding to moderate to moderately severe symptoms 2.2. Anxiety assessed using GAD-7 with a total score between 8 and 21 corresponding to mild to severe symptoms 3. Aged 16 to 64 years 4. If taking psychotropic medication for depression and or anxiety, be on a stable regimen for at least 6 weeks prior to screening with no initiation, discontinuation or dose change during that period 5. Have reliable access to a compatible internet connected device and be able to use it for screening and eligibility, the intervention and assessments with any potential costs clearly noted in the participant information sheet 6. Possess sufficient English language proficiency and cognitive capacity to engage with the digital therapeutic content and complete questionnaires 7. Provide informed consent 8. Be willing to be randomised and to participate in a clinically supervised CBT based AI programme including completion of scheduled outcome assessments |
| Key exclusion criteria | 1. Depression assessed using PHQ-9 or PHQ-A for young people with a total score of 20 or higher 2. Present with a primary or comorbid diagnosis or history that is unsuitable for a digital CBT based intervention as judged by the investigator, including 2.1. Post traumatic stress disorder or complex trauma 2.2. Psychotic disorder, bipolar disorder and or mania 2.3. Complex or treatment resistant obsessive compulsive disorder 2.4. Personality disorder 2.5. Eating disorder 2.6. Substance use disorder or alcohol use disorder 3. Exhibit high risk clinical concerns, including 3.1. Current suicidal ideation with intent or plan as indicated by PHQ-9 score and or participant disclosure 3.2. Suicide attempt within the past 12 months 3.3. Ongoing self harming behaviours 3.4. Requirement for urgent or crisis mental health intervention as indicated by PHQ-9 score and or participant disclosure 4. In participants aged 25 years and under, current treatment with an antidepressant medication that was initiated or dose adjusted within the past 12 weeks due to the recognised increased risk of suicidal thoughts and behaviours during the early phases of antidepressant treatment in this age group 5. Have been referred to or managed by a mental health crisis intervention team or equivalent, or admitted as an inpatient within psychiatric services in the last 12 months 6. Are currently receiving structured psychological therapy for anxiety or depression delivered by another provider 7. Use of medications indicative of severe mental illness or clinical instability, including 7.1. Antipsychotic medication excluding low dose use for non psychiatric indications where clinically appropriate 7.2. Regular use of sedative hypnotic medication such as daily benzodiazepines or Z drugs suggesting clinical instability 7.3. Current or recent use within the past 3 months of psychedelic assisted therapy involving substances such as MDMA, psilocybin or ketamine, where this indicates ongoing clinical instability or participation in an active interventional mental health treatment 8. Participation in another interventional clinical trial or use of investigational drugs in the last 30 days 9. Any other significant disease or disorder which, in the opinion of the investigator, may put the participant at risk because of participation in the trial, influence the results of the trial, or affect the participant’s ability to participate in the trial |
| Date of first enrolment | 01/06/2026 |
| Date of final enrolment | 01/09/2026 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
London
SE1 0HR
England
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan |
Editorial Notes
05/05/2026: Trial's existence confirmed by South Birmingham REC.
