Psychosocial Support for Nitrous Oxide Misuse

Setting This is a feasibility study with nested qualitative interviews conducted by researchers based at Queen Mary University of London (QMUL) and Barts Health NHS Trust (BHNT). Participants are recruited from the N₂O SDEC pathway at the Royal London Hospital (RLH), BHNT.

Design Staged approach to intervention refinement and preliminary testing involving a mixed-methods feasibility and fidelity evaluation, with nested qualitative interviews.

Data Collection Methods Feasibility Evaluation All participants will complete an eligibility screen and provide informed consent before they enter the study. Details of the study will be explained via the Participant Information Sheet (PIS) ensuring that that the patient has sufficient time (at least 24 hours) to consider whether or not to participate. The Clinical Fellow will answer any questions that the patient has concerning study participation via telephone, videoconferencing, or email support. Those who wish to participate will be asked to complete a Consent Form.

Using Case Report Forms (CRF), recruitment figures will be calculated, including:

• Appropriateness of eligibility criteria - monitoring reasons for exclusion.
• Willingness of patients to take part - assessment of the size of the eligible population, refusal, and those that consent to participate.
• Determine success of recruitment strategy - monitoring numbers of patients with whom study was introduced, which research team members were involved, number of patients who expressed an interest in receiving PIS, and content of preliminary discussions/ questions with research team.

Once a participant has been recruited and consented, they will complete the baseline questionnaires. Demographic and clinical information will be extracted from their clinical notes by the Clinical Fellow. This will cover routinely collected data including:

• Demographics: Age, sex, gender, ethnicity, postcode, education, employment status.
• Clinical: Referral date, symptom onset date, presenting complaint, SACD certainty grading, other neurological diagnosis related to N2O use (e.g. peripheral neuropathy, functional neurological disorder), mental health history (current and previous).
• Nitrous Oxide (N₂O) usage: Amount in grams, frequency and duration of use. Reported usage of other drugs.

Research questionnaires include:

• Hospital Anxiety and Depression Scale (HADS)
• Health-related quality of life: EQ5D-5L
• Perceived positive and negative aspects of drug use, and treatment readiness: Drug Use Disorders Identification Test-Extended
• Presence of DSM-5 substance use disorder (SUD) criteria: Substance Use Symptom Checklist
• Resilience and belief in one's ability to handle challenging life demands: General Self-Efficacy Scale

After completing the final intervention session, participants will repeat the questionnaires, where possible within 1-week. Study questionnaires were chosen because they: (i) tap domains of interest identified by PPIE and public networks (ii), relate to content and mechanisms targeted by the psychosocial intervention (therefore likely to be affected by the intervention), (iii) have good psychometric properties, and (iv) are brief and easy to complete. Pilot testing indicates the questionnaires take approximately 20-30 minutes to complete.

Questionnaires will be completed by participants online via Jisc OnlineSurveys or using posted paper copies. Members of the research team will be available to support completion either in-person (RLH), or over the phone. Levels of missing data and data completeness will be monitored and presented as part of the ongoing data collection, cleaning, and reporting processes. Participants will be contacted by a member of the research team (telephone call, email or text) to complete any missing data on questionnaires and provide support if needed, with this contact logged in CRFs. Retention rates will be monitored, and where available reasons for withdrawal or drop-out reported. The research team will also keep a log of any operational issues in delivering the study to inform the design of a subsequent trial and refinement of the intervention.

Fidelity Evaluation Participants will receive usual care (weekly B12 injections for 2-12 weeks alongside clinical investigations and follow-up) plus the psychosocial intervention. The intervention is a manualised, multi-faceted programme involving various components (i.e., information provision, goal setting) and a range of strategies and techniques (e.g., psychoeducation, compensatory strategies, reframing beliefs, emotion regulation). The intervention is person-centred, tailored to the needs and lifestyle of each participant, and aims to help N₂O users cope with and manage psychological distress by establishing strategies that can be maintained once the intervention sessions are finished. Intervention materials include a workbook with accompanying worksheets for participants to reflect and process the content. Please see supporting documents for intervention materials.

The intervention will be delivered by a trained intervention facilitator, under the supervision of a Consultant Liaison Psychiatrist based at BHNT. Face-to-face (RLH, BHNT), videoconferencing, and telephone delivery options will be available according to participant preference. The duration of the intervention will be up to 6 hours, spread across 3-4 sessions (up to 90 minutes each). Sessions will ideally occur on a weekly basis but some flexibility will be afforded for participant availability.

To evaluate intervention fidelity, the intervention facilitator will keep detailed case notes from sessions and complete an intervention record form during/after each session, detailing the duration, content of the therapeutic interaction, and any issues arising. Approximately 35 observations (10 participants, each receiving 3 or 4 sessions) will be captured. This will be sufficient to identify intervention manual deviations and skills that require addressing in training for a definitive RCT trial. Participant worksheets and intervention facilitator record forms and case notes will be reviewed against the intervention manual and preliminary logic model to assess whether key components are delivered as intended and identify challenges in implementation.

The research team will make copies of intervention worksheets completed by participants allowing them to keep a copy to revisit once the intervention sessions are finished (see intervention workbook attached). These will be used to track engagement and inform fidelity e.g. checking whether worksheets relating to different sections of the resource book were completed, checking the content of worksheets to determine whether participants have understood intervention content and are able to apply therapeutic techniques learned in the intervention.

Findings will be used to refine the logic model, intervention documents, and training packages delivered to clinical team members and intervention facilitators, as necessary.

Nested Qualitative Interviews After completing the final intervention session, participants will be invited to the interview. The interviews will be explained within the PIS, and a specific tick box allocated to the interviews will be included on the Consent Form.

Interviews will cover acceptability and experiences of the intervention, components of the intervention, barriers and facilitators to engagement, and experiences of the research process. Interviews will be scheduled within 4-weeks of completion to aid recall and engagement.

Interviews will be semi-structured to allow participants to focus on meaningful issues. An interview topic guide was iteratively developed based on previous research, input from researchers and healthcare professionals, and PPIE with lived experience of N2O harms. Participants will receive a copy of the topic guide ahead of the interview to facilitate discussions (see interview schedule attached).

Participants can choose whether to be interviewed over the phone, via videoconferencing, or face-to-face at RLH or QMUL. Interviews will be audio-recorded using an encrypted Dictaphone and transcribed verbatim by an approved transcription service. Interviewers will also keep field notes to capture contextual information. Perceptions on useability, usefulness, and acceptability of the intervention will be extracted from interview transcripts.

Interviews are likely to take up to 60 minutes. If participants demonstrate that the interview session is causing them discomfort or distress, the research team will check with them whether they wish to continue and proceed only with their permission. Breaks will be provided as needed.

Inclusion criteria

• Confirmed clinical neurological diagnosis related to N₂O use.
• Experiencing mild to moderate psychological distress.
• Aged 16-65 years.
• Able to communicate in English.
• Able and willing to give informed consent.

Exclusion criteria

• Other causes of neurological symptoms.
• Currently receiving another structured psychosocial intervention.
• Severe psychiatric distress.