Aims
The overall aim of this exploratory trial is to test the feasibility of an RCT evaluating the clinical effectiveness of a psychological intervention, compared to usual care, in reducing anxiety in individuals with pre-manifest and early-stage HD.
Specific objectives for the study are as follows:
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Assess the feasibility of recruitment and retention to both arms of the trial (intervention versus treatment as usual) across assessment, intervention and follow-up periods of 3 and 6 months (primary objective).
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Describe participant characteristics and assess generalisability compared to HD population more widely.
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Describe screening assessment results.
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Assess the feasibility of measuring the primary and secondary outcomes and obtain information to inform the sample size for a full RCT.
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Describe and explain the fidelity to the intervention and evaluate views, experiences and acceptability of the participants.
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Investigate the acceptability of the intervention (including to carers) and outcome measures.
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Determine whether criteria to progress to a definitive trial are reached.
Intervention: Rationale And Development
The guided self-help intervention in the treatment arm is based on cognitive-behavioural models of anxiety and is being adapted to meet the specific needs of an HD population. The intervention uses both content and process-based cognitive behaviour therapies, using a recent framework [26] whereby evidence-based processes of change will be targeted. The approach is a blend of traditional CBT and ACT. An HD-specific therapy manual as well as participant booklets have been co-produced with an HD user/carer steering committee. During the intervention, participants will be provided with a toolkit comprising both written and electronic resources containing psychological techniques that are known to help reduce anxiety and designed specifically for HD. Based on individual preferences ascertained at the beginning of therapy, participants will receive either weekly telephone, video call or email guided psychological support across 10 sessions (aimed at weekly sessions lasting 1 hour). Adaptations to standard CBTs will be made to compensate for mild cognitive impairments, including use of external memory aids and behavioural routines. Where applicable, carers/partners will be offered copies of the toolkits to support the participant and will be offered a maximum of three individual sessions with the facilitators across the intervention period, to help them support the pwHD.
The intervention will be provided by a team of three or four mental health practitioners (e.g., nurse or assistant / trainee psychologists). They will receive weekly supervision and three days’ training in the intervention by a clinical psychologist. The team will also receive monthly supervision by the first author (a senior clinical psychologist with expertise in HD).
Individuals and other family members affected by HD have been central to the development of this intervention. Of particular importance has been ensuring the self-help materials address the specific issues raised by people affected by HD during the intervention development process. This adaptation can be broadly described as: acknowledgement of the challenging situations and dilemmas pwHD encounter as they navigate their relationships and social circumstances; the understandable distressing thoughts and feelings that may arise as a result of this; and the actions people undertake to cope. Specific examples include the impact of intergenerational experiences of HD, coping through avoiding reminders of HD, or hypervigilance of potential signs or changes in HD symptoms.
Design And Setting
The design is a two-arm randomised controlled feasibility trial, collecting both quantitative and qualitative data. The study will compare guided self-help with Treatment as Usual (TAU), with an allocation ratio of 1:1 to each arm. All participants will receive treatment as usual and not be suspended from any interventions currently offered or planned. The consort flowchart of this study is shown in Fig. 2.
Participants, Eligibility, Recruitment, And Consent
Participants will primarily be recruited across counties in the East Midlands (Leicestershire, Nottinghamshire, Northamptonshire, Lincolnshire, and Derbyshire) via either local NHS Trusts or by UK HD charities (e.g., Huntington’s Disease Association).
As this is a feasibility study, a formal power calculation is not appropriate given that the parameters for estimation are unclear due to the lack of previous research in this area and the aim is primarily to assess feasibility outcomes. Consequently, we have assumed that 12 participants per group will be sufficient to determine reliably the primary feasibility outcomes [27]. The total recruitment target is set at 30 HD participants (15 per arm) to allow for expected attrition rates.
Participants aged 18 and above who have been confirmed as having the HD gene expansion and a diagnosis of clinical anxiety are eligible for the study. Participants will either be pre-manifest or in the early stages of HD with a Total Functional Capacity (TFC) score of 9–13 [28]. Not every participant will be taking medications known to impact on anxiety (e.g., an antidepressant medication or a benzodiazepine agent), however if they have commenced a pharmacological treatment, it must be stabilised for at least 4 weeks before the participant is recruited into the study. This is to ensure that potential changes in anxiety across the course of the study are not solely due to medications. Participants need to be able to read/understand English and be able and willing to give informed consent. Individuals who identify as providing informal (not paid) care for someone with HD will also be recruited into the study. They will be 18 years and above and have had some involvement in the intervention. They must be able to give informed consent.
Figure 1 shows the data collection timetable.
Procedure
For recruitment through the NHS, relevant clinical staff will identify any potential participants who appear to meet the inclusion criteria. For participants who express an interest, clinical staff will give a letter of introduction, a participant information sheet and a 'consent to contact' form with a stamped addressed envelope. Alternatively, potential participants will be given the option to contact the research team directly or will give verbal consent for the clinical staff member to pass on their contact details to the research team. For participants recruited via charities, the research will be advertised through websites and social media announcements. On this information, contact details for the research team will be given.
On contact with the research team, potential participants with HD will initially be checked for basic eligibility criteria by an initial telephone interview. If a person meets those basic criteria, then consent will be taken to proceed to the next step of the project. This will involve a clinical diagnostic interview with a clinical psychologist which will be undertaken at a time convenient for the participants, to ascertain whether they meet Diagnostic and Statistical Manual of Mental Disorders (DSM-V; [29]) criteria for an anxiety disorder; this is needed to establish whether full criteria for eligibility will be met. Clinically relevant information gained from this interview will also form part of the treatment formulation plan for those who are allocated to the intervention arm of the study. At this assessment point, if the threshold for an anxiety disorder is reached, then cognitive functioning will also be assessed using a brief measure (the Montreal Cognitive Assessment, MoCA; [30]). The purpose of this measure is both to characterise the sample and enable therapists to understand any difficulties so the intervention can be tailored appropriately. The clinical psychologist will also make a judgement, based on both the cognitive assessment, and the interview whether the potential participant fits the eligibility for cognitive and communication abilities necessary to proceed with the intervention.
Potential participants will be asked whether they have a friend/carer/family member whom they would like to be involved to support them with the intervention. They will be asked for the identified person to contact the research team to confirm if they wish to be involved. However, having a carer involved is not a requirement for eligibility for the study. The research associate will then either meet with the HD participants or, depending on any current COVID-19 regulations and participant preference, via videoconferencing to collect baseline data using outcome measures for anxiety, depression, irritability, quality of life, functional capacity, HD related concerns, psychological flexibility, and coping. Brief demographic and clinical data will also be gathered. If participants would prefer to complete the measures themselves (except the Hamilton Anxiety Rating Scale (HAM-A; [31]), which is clinician-administered), they will have the option to complete the measures themselves; this will be either available as online or posted to them and they will be given a stamped addressed envelope to return the forms. Participants in the intervention arm will receive the guided self-help in addition to their usual care.
The study will adhere to the NHS Code of Confidentiality and will comply with General Data Protection Regulation (GDPR 2018). All information provided in the study will be kept confidential. Exceptions to this would be if a disclosure involving significant risk of harm to self or others were made, in which case the relevant authorities would be informed. No personal identifiable data will be transferred to other members of the research team. All documents will be stored securely and will only be accessible by the study team and authorised personnel.
Data collection and management
We will collect both quantitative and qualitative data as part of this study. In addition to the quantitative data taken, participants will also be invited to participate in a qualitative evaluation, along with any carers who supported the participants.
Each participant will be assigned a study code. We will use this code to enter the data into an Excel database Once data collection is complete, this will be transferred to SPSS for analysis All databases will be password encrypted and pseudo-anonymised. All participants will be assigned a unique ID number and a separate document linking ID numbers to their actual identities will also be stored in a locked cabinet in a locked office in the first author’s workplace. Electronic information will be stored securely on NHS computers and will be anonymised with ID numbers held on a separate file to those of the participants' identity.
The anonymised data will be used for analysis purposes and will be shared securely with other members of the study team and as required by our funders. Qualitative data will be in the form of audio recordings and verbatim anonymised transcripts.
Anonymised transcripts will refer to speakers as interviewers and participants; documents will be password protected before sharing amongst members of the team.
Participants will be allowed to withdraw from the study at the point of consent and during the study recruitment period. However, at the point of data anonymisation and analysis, it will no longer be possible to withdraw participants from the study. Following completion of the study, we will archive the data for the time period of five years. We will also ensure that data are prepared and shared in keeping with the rules and regulations of the Jacques and Gloria Gossweiler Foundation, the funder.
Outcome measures
All participants will be assessed for anxiety using the HADS-Anxiety subscale [32] and Hamilton Anxiety Rating Scale (HAM-A; [33]). Reductions on these measures would be the expected primary outcomes of a full RCT. Prior to randomisation, measures will also be collected on depression (HADS-D; [32]), irritability (Snaith Irritability Scale; [34]), quality of life (HD-QoL; [35]), functional ability (UHDRS TFC; [28]). The putative process or mechanism measures are the HD Concerns Questionnaire [36], a measure of coping (the brief COPE; [37]), and psychological flexibility (AAQ; [38]).
Participants will be asked to complete the questionnaires at baseline, immediately after the intervention, and at 3-month and 6-month follow-ups. They will also be asked to undertake Likert rating scales to report the acceptability of the intervention and outcome measures. These will be given at 2-week post-intervention to rate the intervention and 6 months to rate the outcome measures.
Feasibility outcomes
To meet the primary objective of determining feasibility of recruitment and retention, descriptive statistics will be used. To measure recruitment, we will analyse the percentage of participants identified as eligible who consent to the study. In order to assess feasibility of retention, we will look at the percentage of those recruited to the study who remain in the study at timepoints of 1) after initial assessment session, 2) at the end of the intervention period 3) at 3-month follow-up, and at 4) 6-month follow-up
Randomisation & Blinding
Members of the research team separate from those collecting the pre-intervention data will undertake a stratified randomisation process using an automated online randomisation system, with participants allocated to either the intervention arm or TAU. The stratification for this randomisation is to ensure that premanifest and manifest HD participants are distributed equally across both groups.
Data analysis
To meet the primary objective of determining feasibility of recruitment and retention, descriptive statistics will be used. For the secondary objective of investigating the acceptability of both the intervention and outcome measures, both quantitative and qualitative analysis will be undertaken. For the quantitative analysis, descriptive statistics will also be used to report on findings from the Likert scales. For acceptability of intervention, we will examine the percentage of those who reported each score on a 0–5 Likert scale for readability, clarity, effort, enjoyment, concentration, helpfulness, progress regarding therapy materials, and overall acceptability. Adherence to the intervention will also be analysed through descriptive statistics, examining the percentage of activities required by the intervention that are undertaken during the therapy. For the quantitative analysis for acceptability and suitability of outcome measures, the percentage of the different scores on a 0–5 Likert scale will be analysed, as well as the percentage of those who were willing to complete the outcome measures. Analysis for our final objective - to assess the feasibility criteria from which to progress to a definitive trial, potential clinical effectiveness, and putative mechanisms – will be quantitative, but will also be informed by feedback from the qualitative analysis above.
Qualitative analysis will also be used to assess the acceptability of the intervention and outcome measures. Both HD participants and carers in the intervention arm will be interviewed individually within 1-month post-intervention. This will be to gain information regarding experiences of the intervention across the known key parameters of intervention delivery. Data will be digitally recorded, anonymised and transcribed. Framework analysis [39] will be used as this provides an efficient, focused approach involving specific questions to discuss pre-identified issues [40]. Computer assisted qualitative data analysis software (e.g., NVivo) may be used to categorise the data.