Preliminary Randomised Evaluation of Singing in Dementia

PURPOSE The purpose of PRESIDE is to test the feasibility of conducting a randomised trial of community singing in dementia that investigates the effects of singing on quality of life and explores the impact singing groups have on the relationship between the person with dementia (PwD) and carer.

PRIMARY OBJECTIVE The primary objective of the PRESIDE study is to test the protocol for a two-arm, parallel group superiority randomised trial of community singing in dementia with a waiting-list control design. The relevant indicators are recruitment, retention, and the acceptability of the trial design.

SECONDARY OBJECTIVES The secondary objective of the study is to explore the impact of group singing on PwD and their carers. This would improve understanding of the mechanisms of action in group singing for PwD and potentially indicate suitable outcome measures for full-scale trial.

DATA COLLECTION A mixed-method design will be applied to collect data using questionnaires, semi-structured interviews and observations.

PRIMARY END POINT The attainment of the feasibility criteria at 6 months is the primary end point for PRESIDE. Proposed criteria for proceeding to a full trial: 70% recruitment; 70% retention of participants over 3 months; and acceptability of waiting-list controls shown by 70% singing group take-up post waiting-list period.

SECONDARY ENDPOINT The secondary endpoint is the measurement of social independence, loneliness, quality of life, activities of daily living, mood, musical engagement and cognition of PwD; the measurement of quality of life, loneliness, mood, caring relationship and experience of carers. Each dyad's use of health social care services and resources will also be documented. Follow-up data will be collected at 3 months after baseline to compare the difference between the intervention and control groups, and 6 months to investigate the sustainability of any treatment effect. Further, to better understand the experiences of dyads who attend the singing group, qualitative data will be collected using interviews and participant observation.

STOPPING RULES AND DISCONTINUATION The intervention will be stopped if a Serious Adverse Event (SAE) occurs which is judged to be directly related to the trial and likely to affect other participants. This decision will be taken by the DMEC.

Individual participants may withdraw from the trial at any time and their reasons for withdrawal will be recorded if they are willing to give them. The Trial Steering Committee would decide whether to continue if recruitment figures were poor.

RANDOMIZATION AND BLINDING Participants will consist of a PwD and their carer, with stratification on MMSE score and minimisation on age, sex and MusEQ score. Baseline data will be collected by members of the Clinical Research Network (CRN) for all recruited pairs prior to randomisation. Randomised pairs will be assigned to either the intervention group or the waiting-list control group. Follow-up data collection at 3 and 6 months will be undertaken by members of the CRN, who will be blind to group allocation. However, there is the possibility that since the study participants will know their own allocation, they may reveal this during the follow-up data collection. Any unblinding of outcome assessors which occurs in this way will be recorded, as it has implications for the feasibility of the study design.

Randomisation will be performed by a web application created by the trial programmer at the University of Nottingham Stroke Trials Unit, using web and database servers provided by University of Nottingham Information Services (IS).

The research team will be divided in the data management group, who will not be blinded to group allocation (intervention or waiting list control) for logistical reasons (data collection, anonymising data and running of the study), and the analysis group, who will be blinded throughout the study and have no contact with study participants. Allocation will only be revealed to blinded members of the research team in the case of emergencies (i.e. SAEs). In this case the Chief Investigators and Data Monitoring and Ethics Committee will be informed.

PARTICIPANT AND STUDY DURATION The study will last two years. Participant involved is anticipated to be between 9 and 12 months. The end of the trial will be the final assessment of the last participant with dementia and their carer.

After recruitment and baseline data collection, participants will either attend a singing group for ten weeks or wait for 12-13 weeks before attending a singing group for ten weeks. They will receive follow up at 3 months and 6 months after baseline.

RECRUITMENT Recruitment will be multi-channelled: PRESIDE posters and a cover letter will be sent for distribution to people who have recently been diagnosed with dementia via NHS Memory Assessment Services and PwD who are currently on the waiting list for Singing for the Brain sessions via the Alzheimer's Society. Local community organisations, charities and local press (Radio Nottingham, Nottingham Post and similar) will also be utilised, and social media advertising will be part of the recruitment campaign. Recruitment will be undertaken using the online platform "Join Dementia Research".

Regional recruitment may also take place through having PICs within primary care, with the support of the NIHR CRN for GP surgeries. Eligible participants will be screened from a database by a member of the direct care team at that practice. Participants that meet the inclusion and exclusion criteria will be invited to join the study through letter invitation from their GP surgery. Participants who contact the research team post invitation, will then be provided with study specific information by the research team.

Participants may contact the research team directly to express interest in taking part in the study, for example, in response to advertisement.

EXPRESSION OF INTEREST AND PARTICIPANT INFORMATION Potential participants who are eligible and interested in taking part will receive a PRESIDE Participant Information Sheet (PIS). They will have the opportunity to read the information and to speak to members of the research team. If they wish to proceed with involvement in the study, they will receive a visit from a PRESIDE research member. This will take place at a convenient location, such as their home or other venue. The researcher will fully explore the implications of participation in the study and confirm their eligibility. They will be provided with a consent form which they will sign if they choose to continue with participation. Following consent, the researcher will enrol the participant dyad and complete baseline outcome measures at the same visit.

The research or their nominee (such as the participant's usual care team) will inform the participant, of all aspects pertaining to participation in the study. If needed, the usual hospital interpreter and translator services will be available to assist with discussion of the trial, the PIS, and consent forms. However, consent forms and information sheets will not be available in other languages since understanding English is an inclusion-criteria for this study.

It will be explained to the potential participant that entry into the trial is entirely voluntary, that their treatment and care will not be affected by their decision and that they can withdraw at any time. Participants will be made aware that should they withdraw, anonymised data already collected cannot be erased and may still be used in the final analysis.

REMOVAL OF PARTICIPANTS AND PARTICIPANT WITHDRAWAL Temporary discontinuation might happen if either participant (PwD or carer) from the dyad is unavailable, indisposed or does not want to join the session on a specific day. Participants may withdraw from the study at any time, without providing any reason. Carer participant withdrawal would result in the participant with dementia being re-paired with a different person. Withdrawal from a PwD.

would result in withdrawal of the dyad. However, the carer participant would still be able to attend the allocated singing sessions if they wished. Participants may also be withdrawn from the study at the discretion of the Investigator.

Participants who have lost capacity to consent but have remained part of the study (see section on Informed Consent below) will be immediately and permanently withdrawn from the study if they show observable signs of dissent or discomfort or it is reported from their carer. Participants will be made aware that withdrawal will not affect their future care.

Abrupt termination of the study is unlikely to affect the participant safety as the study focus on an entertainment social intervention. Failure to recruit sufficient participants could lead to termination of a specific regional group. In this instance, participants would be offered another group to join.

INFORMED CONSENT The Consent Form will be signed and dated by the participant before they enter the trial. PIS and, when appropriate, a dementia friendly booklet will be provided for PwD and carers. Fully informed consent will be taken at the initial study visit by trained and experienced members (CRN or PRESIDE) that hold a valid Good Clinical Practice Certificate (NIHR). Absolute care will be taken to ensure that participants fully understand the study and their involvement.

PwD who do not have capacity to provide informed consent at the start of the study will be excluded from the study. Due to the progressive nature of dementia, Dewing's 'process consent model' is applied so there is periodical assessment of capacity and consent is continuous and ongoing.

If a participant with dementia loses capacity during the trial period, where appropriate, the carer participant in the dyad would be asked to act as consultee. If the carer participant is a paid carer, then this would not be appropriate and a consultee declaration from the most appropriate person for this individual would be sought. The consultee will be provided with information about their role within the parameters of the study and will be asked to make a judgement about whether they would have wanted to continue to take part in the study. If they judge that the PwD would have wanted to continue to take part, the consultee will sign a declaration form to indicate this. In the unlikely event that a PwD was judged to have regained capacity during the trial period, the research team would discuss with them to ascertain whether they wished to continue in the study.

We shall treat the consent of carers equally rigorously. Should a carer lose capacity to consent during the trial period, a consultee will be sought for them. In this situation, the continuation of a dyad in the study will be at the CI's discretion.

METHODS Data analysis will be conducted by a statistician using Stata 16 software. All measures will be summarised with mean (S.D.) for normally distributed variables, median (IQR) for skewed variables and frequency (%) for response of categorical variable, by intervention arm across follow-up time. ANCOVA will be performed to quantify treatment effect size and its precision by means of regression modelling with baseline measures as covariate, and to derive the change from baseline score for each arm. Due to the non-independence of patient-carer dyad measures and data being measured repeatedly, multivariate multilevel modelling will be performed to account for the association between same kind of outcome measure of patient-carer data and repeated data. Data will calculate recruitment rate, retention rate and attrition rate, exploring patterns of missing data and drop out from the waiting list control group. All results will be used to inform future definitive trial design. All data will be analysed on UoN computers and backed up to the UoN servers.