The goal of this clinical trial is to assess the feasibility and acceptability of a multi-component smoking cessation intervention for individuals living with diabetes which is delivered by diabetes specialist nurses. The main question it aims to answer is:

Is a diabetes specialist nurse-led multi-component smoking cessation intervention tailored for persons living with diabetes who smoke feasible and acceptable among the providers and the participants, the individuals with diabetes?

Eligible individuals living with diabetes who smoke will be asked to participate in a feasibility study lasting twelve weeks. The participants will be allocated at random either to the diabetes specialist nurse-led multi-component smoking cessation intervention, or to standard care - an active referral to the Health Promotion and Disease Prevention Directorate's one-to-one smoking cessation service. The multi-component smoking cessation intervention will be provided by the diabetes specialist nurses at the Diabetes Education Unit at Mater Dei Hospital. The Health Promotion and Disease Prevention Directorate's one-to-one smoking cessation service is provided by tobacco cessation facilitators within the health centres of Mosta, Floriana, and Paola. Both interventions will help participants re-consider their smoking habits and support them to quit smoking, free of charge.

Primarily the researchers will:

• assess the feasibility of a largescale randomized controlled trial, by analyzing the recruitment and study uptake, and the nurses' perceived challenges and facilitators to implementation;
• and assess the acceptability of the intervention, by analyzing the nurses' feedback and the participants' satisfaction with and perceived usefulness of the smoking cessation intervention provided, in comparison to the satisfaction with standard care - the Health Promotion and Disease Prevention Directorate's one-to-one smoking cessation service.

BACKGROUND

Smoking cessation is an important aspect of diabetes management. Smoking worsens the cardiometabolic parameters of both individuals with type 1 and type 2 diabetes, significantly increasing the risk of various macro- and micro-vascular complications, and even death. Smoking cessation is associated with improved cardiometabolic values and a reduced risk of cardiovascular complications. However, evidence suggests that people living with diabetes may less likely quit smoking when compared to those without diabetes.

While the need for providing tailored smoking cessation support for those who have diabetes has been emphasized, evidence-based smoking cessation recommendations for such individuals are lacking. In addition, the literature suggests that diabetes educators tend to focus on other aspects of diabetes management, rather than tobacco use. Diabetes educators have reported feeling inadequately prepared in discussing smoking cessation amongst individuals with diabetes lacking motivation and time to do so.

STUDY AIM AND OBJECTIVES

The aim of this randomized controlled feasibility study is to establish the feasibility and acceptability of a diabetes specialist nurse-led smoking cessation intervention, based on evidence and theory, tailored for people living with diabetes.

The primary objectives are to:

• assess the feasibility of a large-scale randomized controlled trial, by analyzing the recruitment and study uptake, and the nurses' perceived challenges and facilitators to implementation;
• and assess the acceptability of the intervention, by analyzing the participants' satisfaction with and perceived usefulness of the smoking cessation support provided, and the nurses' feedback.

The secondary objectives are to:

• compare the participants' satisfaction with and perceived usefulness of the smoking cessation support provided to standard care - the provision of general smoking cessation support;
• undergo a preliminary process evaluation, by assessing whether the intervention was delivered as intended and exploring the intervention's functioning;
• and determine the preliminary evidence of the intervention's effectiveness, by comparing the smoking cessation rates achieved in the intervention group to the control group (standard care).

METHODS

Design

An open-label, two-arm randomized controlled trial.

Participants

Participants (individuals with diabetes) will be recruited from the Diabetes Education Unit and the Diabetes and Endocrine Centre (MOP2) at Mater Dei Hospital in Malta. The diabetes specialist nurses at the Diabetes Education Unit and the diabetologists and health care professionals at MOP2 will be identifying attending smokers, recruiting those who are interested to the study. Posters and flyers will also be present at MOP2 so that participants can also self-refer to the study. For feasibility studies, 30 to 60 participants per group have been suggested. Given that the sample size decision must also take into consideration the resources required and the time available, this study aims to recruit between 80 to 100 participants in total over a 12 month-period.

Implementation and data collection methods

The Principal Investigator (PI) will screen all recruited patients to determine eligibility and obtain informed consent. Demographic data, the participants' perceived health status, their diabetes and smoking profiles, and reported feelings in the past week will be assessed using a questionnaire. Exhaled carbon monoxide will also be measured using the Bedfont piCO™ Smokerlyzer®. Participants will then be randomly allocated to the intervention or control arm on a 1:1 ratio using a computer-generated random block length, which will be concealed to the PI.

The participants assigned to the intervention group will receive a tailored smoking cessation intervention for individuals with diabetes based on evidence and theory and guided by the 5A's (Ask, Advise, Assess, Assist and Arrange) and 5R's (Relevance, Risks, Rewards, Roadblocks, and Repetition) framework for smoking cessation. This will consist of three to four (30-60 minutes) smoking cessation support sessions which will be provided by the two diabetes specialist nurses at the Diabetes Education Unit during the study period (12 weeks). As part of the first session, participants will also be shown three very brief video clips in which a person living with diabetes explains the serious health problems he suffered from (when smoking and having diabetes). Participants will also receive a six-week supply of Nicotine Replacement Therapy (NRT) - nicotine patch and/or nicotine spray. Conversely, the participants who are assigned to the control group will be actively referred to the Health Promotion and Disease Prevention Directorate's one-to-one smoking cessation service which is provided by tobacco cessation facilitators at Mosta, Floriana, or Paola health centres. These participants will be provided with a number of smoking cessation sessions (20 minutes each) based on their needs, provided every fortnight during the 12-week study period.

To help capture fidelity, all the sessions provided by the diabetes specialist nurses will be audio-recorded with consent. The nurses, who will provide the experimental intervention, will also be asked to document the following information per participant:

• the number (and duration) of the sessions provided (and the total time period [in weeks] during which the sessions were provided);
• whether the participant opted not to see the informational video clips (with reasons);
• whether the participant agreed to attempt to quit smoking (by setting a Target Quit Date, TQD) at their first session, (and subsequent session if still smoking), with reasons for not wanting to;
• provision of the 5R's intervention at the first session;
• non-attendance (and reasons);
• the amount of NRT provided (and returned);
• reported use of NRT (with reasons if a participant reports not using it) - including the total number of days of the nicotine patch and/or spray use (and the average use of the nicotine spray/day) during the first week following the TQD (and the subsequent TQD for those who agree to reattempt quitting), and in the next four weeks;
• any problems encountered (such as side effects on using NRT, identified mental health issues, issues with managing diabetes, and any referrals, [including reasons for refusing support]).

The tobacco cessation officer at the Health Promotion and Disease Prevention Directorate will also be asked to take note of the number of sessions provided (including the total time period during which the sessions were provided) and any dropouts (with reasons).

At the end of the study period, all participants will be asked to fill in the end-of-study questionnaire (to assess smoking and measure abstinence, characterize the support utilized, and investigate the participants' satisfaction with and perceived usefulness of the smoking cessation intervention provided). For those who report quitting smoking (for at least seven days prior to assessment), biochemical verification of tobacco abstinence will be carried out by using the Bedfont piCO™ Smokerlyzer®, and analyzing a urine sample for cotinine exposure using a multilevel lateral flow immunoassays urine test strip with a nominal 200 ng/mL cutoff.

Semi-structured interviews will also be carried out with a sample (15-20) of the study intervention participants to obtain feedback on the study intervention and to explore their quit attempts. Semi-structured interviews will also be carried out with the two diabetes specialist nurses to obtain feedback on the study intervention and to explore the facilitators and challenges to implementation.

Data analysis

Recruitment - The average number of participants recruited per month and the total time period taken to recruit all participants will be calculated. Reasons for ineligibility or for not consenting to participate to the study will be noted. The number of eligible individuals who accept to participate in the study out of those who show interest will be calculated with 95% Confidence Intervals (CIs).

Study questionnaires - Quantitative data, collected at baseline and at the end of the study period, will be analyzed per study group using descriptive statistics. For categorical data, frequencies and proportions/percentages will be used. Continuous data will be summarised using mean and standard deviation, or median and range or interquartile range. Qualitative data will be summarised by following the Applied Thematic Analysis (ATA) approach. The questionnaires' response rate at 12 weeks follow-up, the participants' satisfaction with and perceived usefulness of the smoking cessation intervention provided, and the smoking cessation outcomes, will also be reported using 95% CIs. Intention-to-treat analysis will be used; smokers who can not be reached or are lost to follow-up will be considered non-quitters and non-reducers. The baseline characteristics of those followed up and those lost to follow-up will be compared descriptively.

Interviews - The audio-recorded interviews will be transcribed verbatim, anonymized, and analyzed using ATA.

To provide a further understanding of the acceptability of the study intervention and its functioning as experienced by the study participants (individuals with diabetes) the quantitative and qualitative data will be compared for confirming, disconfirming, or expanding each other.

Audio recording of the provision of the study intervention - To assess fidelity, a random sample (20%) from all the audio recordings of the sessions provided by each provider will be selected. By using a checklist that outlines the study algorithm's components, the occurrence or non-occurrence of these steps will be scored for calculating the level of adherence. Any deviations from the study protocol will also be taken note of.

Intervention log - The rate of compliance to the provided interventions, i.e. the attendance rate to the scheduled sessions, and the reported use of NRT (intervention group only) will be noted. The latter includes the average percentage of days the nicotine patch and/or spray were used (and the average use of the nicotine spray/day) during the first week following the TQD (and the subsequent TQD for those who agree to reattempt quitting), and in the next four weeks. Reasons for non-attendance/not using NRT will be noted. The number of participants who opt not to see the informational video clips and the number of participants who do not want to set a TQD at their first session (and the subsequent session if they report still smoking) will also be noted (with reasons). In terms of resources utilized, the proportion of participants from the intervention group who are provided with the 5R's intervention, the total and average number of sessions provided (in both groups) and the average time period over which these are provided will be calculated. The average time taken to deliver the sessions in the intervention group will also be calculated. In addition, the total and average amount of NRT which are provided (taking note of any returned items) will be calculated (intervention group). Proportions/rates and means with standard deviation will be reported using 95% CIs. Any problems (including reported adverse events) identified by the nurses (and referrals) will be quantified. Participants who refuse additional support will be noted (with reasons).

Ethical clearance for this study was sought from the Faculty of Health Sciences Research Ethics Committee on behalf of the University Research Ethics Committee (UREC FORM V_15062020 8618)

Inclusion Criteria:

• Living with type 1 or type 2 diabetes and attending the Diabetes Education Unit or the Diabetes and Endocrine Centre (MOP2) at Mater Dei Hospital on an outpatient basis
• Having smoked ≥100 cigarettes during his/her entire life and currently smoking (having at least smoked one tobacco product over the past 7 days)
• Being ≥ 18 years old
• Speaking and understanding English or Maltese
• Able to provide written informed consent

Exclusion Criteria:

• Not being able to provide informed consent (due to dementia, a learning disability, or a psychological disorder)
• Being pregnant or breastfeeding
• Unable to independently attend to the Diabetes Education Unit and the Mosta, Floriana, or Paola health centres in Malta during the 12-week study period
• Currently enrolled in another smoking cessation study/program or multi-behavioral program which also focuses on smoking cessation
• Enrolment of the investigator or the research collaborators, and their family members