Botulinum toxins for the prevention of migraine in adults

BackgroundMigraine occurs in around 15% of adults and is ranked as the seventh most disabling disease amongst all diseases globally. Despite the available treatments many people suffer prolonged and frequent attacks which have a major impact on their quality of life. Chronic migraine is defined as 15 or more days of headache per month, at least eight of those days being migraine. People with episodic migraine have fewer than 15 headache days per month. Botulinum toxin type A has been licensed in some countries for chronic migraine treatment, due to the results of just two trials.ObjectivesTo assess the effects of botulinum toxins versus placebo or active treatment for the prevention or reduction in frequency of chronic or episodic migraine in adults.Search methodsWe searched CENTRAL, MEDLINE & MEDLINE in Process, Embase, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry (to December 2017). We examined reference lists and carried out citation searches on key publications. We sent correspondence to major manufacturers of botulinum toxin.Selection criteriaRandomised, double‐blind, controlled trials of botulinum toxin (any sero‐type) injections into the head and neck for prophylaxis of chronic or episodic migraine in adults. Eligible comparators were placebo, alternative prophylactic agent or different dose of botulinum toxin.Data collection and analysisTwo review authors independently selected trials and extracted data. For continuous outcomes we used mean change data when available. For dichotomous data we calculated risk ratios (RRs). We used data from the 12‐week post‐treatment follow‐up time point. We assessed the evidence using GRADE and created two 'Summary of findings' tables.Main resultsDescription of trialsWe found 90 articles describing 28 trials (4190 participants), which were eligible for inclusion. The longest treatment duration was three rounds of injections with three months between treatments, so we could not analyse long‐term effects. For the primary analyses, we pooled data from both chronic and episodic participant populations. Where possible, we also separated data into chronic migraine, episodic migraine and ‘mixed group’ classification subgroups. Most trials (21 out of 28) were small (fewer than 50 participants per trial arm). The risk of bias for included trials was low or unclear across most domains, with some trials reporting a high risk of bias for incomplete outcome data and selective outcome reporting.Botulinum toxin versus placeboTwenty‐three trials compared botulinum toxin with placebo. Botulinum toxin may reduce the number of migraine days per month in the chronic migraine population by 3.1 days (95% confidence interval (CI) ‐4.7 to ‐1.4, 4 trials, 1497 participants, low‐quality evidence). This was reduced to ‐2 days (95% CI ‐2.8 to ‐1.1, 2 trials, 1384 participants; moderate‐quality evidence) when we removed small trials.A single trial of people with episodic migraine (N = 418) showed no difference between groups for this outcome measure (P = 0.49).In the chronic migraine population, botulinum toxin reduces the number of headache days per month by 1.9 days (95% CI ‐2.7 to ‐1.0, 2 trials, 1384 participants, high‐quality evidence). We did not find evidence of a difference in the number of migraine attacks for both chronic and episodic migraine participants (6 trials, N = 2004, P = 0.30, low‐quality evidence). For the population of both chronic and episodic migraine participants a reduction in severity of migraine rated during clinical visits, on a 10 cm visual analogue scale (VAS) of 3.3 cm (95% CI ‐4.2 to ‐2.5, very low‐quality evidence) in favour of botulinum toxin treatment came from four small trials (N = 209); better reporting of this outcome measure from the additional eight trials that recorded it may have improved our confidence in the pooled estimate. Global assessment and quality‐of‐life measures were poorly reported and it was not possible to carry out statistical analysis of these outcome measures. Analysis of adverse events showed an increase in the risk ratio with treatment with botulinum toxin over placebo 30% (RR 1.28, 95% CI 1.12 to 1.47, moderate‐quality evidence). For every 100 participants 60 experienced an adverse event in the botulinum toxin group compared with 47 in the placebo group.Botulinum toxin versus other prophylactic agentThree trials studied comparisons with alternative oral prophylactic medications. Meta‐analyses were not possible for number of migraine days, number of headache days or number of migraine attacks due to insufficient data, but individually trials reported no differences between groups for a variety of efficacy measures in the population of both chronic and episodic migraine participants. The global impression of disease measured using Migraine Disability Assessment (MIDAS) scores were reported from two trials that showed no difference between groups. Compared with oral treatments, botulinum toxin showed no between‐group difference in the risk of adverse events (2 trials, N = 114, very low‐quality evidence). The relative risk reduction (RRR) for withdrawing from botulinum toxin due to adverse events compared with the alternative prophylactic agent was 72% (P = 0.02, 2 trials, N = 119).Dosing trialsThere were insufficient data available for the comparison of different doses.Quality of the evidenceThe quality of the evidence assessed using GRADE methods was varied but mostly very low; the quality of the evidence for the placebo and active control comparisons was low and very low, respectively for the primary outcome measure. Small trial size, high risk of bias and unexplained heterogeneity were common reasons for downgrading the quality of the evidence.Authors' conclusionsIn chronic migraine, botulinum toxin type A may reduce the number of migraine days per month by 2 days compared with placebo treatment. Non‐serious adverse events were probably experienced by 60/100 participants in the treated group compared with 47/100 in the placebo group. For people with episodic migraine, we remain uncertain whether or not this treatment is effective because the quality of this limited evidence is very low. Better reporting of outcome measures in published trials would provide a more complete evidence base on which to draw conclusions

Practice nurse-supported weight self-management delivered within the national child immunisation programme for postnatal women:a feasibility cluster RCT

Background: Pregnancy is a high-risk time for excessive weight gain. The rising prevalence of obesity in women, combined with excess weight gain during pregnancy, means that there are more women with obesity in the postnatal period. This can have adverse health consequences for women in later life and increases the health risks during subsequent pregnancies. Objective: The primary aim was to produce evidence of whether or not a Phase III trial of a brief weight management intervention, in which postnatal women are encouraged by practice nurses as part of the national child immunisation programme to self-monitor their weight and use an online weight management programme, is feasible and acceptable. Design: The research involved a cluster randomised controlled feasibility trial and two semistructured interview studies with intervention participants and practice nurses who delivered the intervention. Trial data were collected at baseline and 3 months later. The interview studies took place after trial follow-up. Setting: The trial took place in Birmingham, UK. Participants: Twenty-eight postnatal women who were overweight/obese were recruited via Birmingham Women’s Hospital or general practices. Nine intervention participants and seven nurses were interviewed. Interventions: The intervention was delivered in the context of the national child immunisation programme. The intervention group were offered brief support that encouraged self-management of weight when they attended their practice to have their child immunised at 2, 3 and 4 months of age. The intervention involved the provision of motivation and support by nurses to encourage participants to make healthier lifestyle choices through self-monitoring of weight and signposting to an online weight management programme. The role of the nurse was to provide regular external accountability for weight loss. Women were asked to weigh themselves weekly and record this on a record card in their child’s health record (‘red book’) or using the online programme. The behavioural goal was for women to lose 0.5-1 kg per week. The usual-care group received a healthy lifestyle leaflet. Main outcome measures: The primary outcome was the feasibility of a Phase III trial to test the effectiveness of the intervention, as assessed against three traffic-light stop-go criteria (recruitment, adherence to regular self-weighing and registration with an online weight management programme). Results: The traffic-light criteria results were red for recruitment (28/80, 35% of target), amber for registration with the online weight loss programme (9/16, 56%) and green for adherence to weekly self-weighing (10/16, 63%). Nurses delivered the intervention with high fidelity. In the qualitative studies, participants indicated that the intervention was acceptable to them and they welcomed receiving support to lose weight at their child immunisation appointments. Although nurses raised some caveats to implementation, they felt that the intervention was easy to deliver and that it would motivate postnatal women to lose weight. Limitations: Fewer participants were recruited than planned. Conclusions: Although women and practice nurses responded well to the intervention and adherence to self-weighing was high, recruitment was challenging and there is scope to improve engagement with the intervention.Future work: Future research should focus on investigating other methods of recruitment and, thereafter, testing the effectiveness of the intervention.Trial registration: Current Controlled Trials ISRCTN12209332.Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 49. See the NIHR Journals Library website for further project information.</p

Treatment of fatigue with physical activity and behavioural change support in vasculitis: Study protocol for an open-label randomised controlled feasibility study

© 2018 Author(s) (or their employer(s)). Introduction Fatigue is a major cause of morbidity, limiting quality of life, in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The aetiology of fatigue is multifactorial; biological and psychosocial mediators, such as sleep deprivation, pain and anxiety and depression, are important and may be improved by increasing physical activity. Current self-management advice is based on expert opinion and is poorly adhered to. This study aims to investigate the feasibility of increasing physical activity using a programme of direct contact and telephone support, to provide patient education, encourage behaviour self-monitoring and the development of an individual change plan with defined goals and feedback to treat fatigue compared with standard of care to inform the design of a large randomised controlled trial to test the efficacy and cost effectiveness of this programme. Methods and analysis Patients with AAV and significant levels of fatigue (patient self-report using multidimensional fatigue index score questionnaire ≥14) will be randomised in a 1:1 ratio to the physical activity programme supported by behavioural change techniques or standard of care. The intervention programme will consist of 8 visits of supervised activity sessions and 12 telephone support calls over 12 weeks with the aim of increasing physical activity to the level advised by government guidelines. Assessment visits will be performed at baseline, 12, 24 and 52 weeks. The study will assess the feasibility of recruitment, retention, the acceptability, adherence and safety of the intervention, and collect data on various assessment tools to inform the design of a large definitive trial. A nested qualitative study will explore patient experience of the trial through focus groups or interviews. Ethics and dissemination All required ethical and regulatory approvals have been obtained. Findings will be disseminated through conference presentations, patient networks and academic publications

Short course daily prednisolone therapy during an upper respiratory tract infection in children with relapsing steroid-sensitive nephrotic syndrome (PREDNOS 2):protocol for a randomised controlled trial

BACKGROUND: Relapses of childhood steroid-sensitive nephrotic syndrome (SSNS) are treated with a 4- to 8-week course of high-dose oral prednisolone, which may be associated with significant adverse effects. There is a clear association between upper respiratory tract infection (URTI) and relapse development. Previous studies in developing nations have suggested that introducing a 5- to 7-day course of daily prednisolone during an URTI may prevent a relapse developing and the need for a treatment course of high-dose prednisolone. The aim of PREDNOS 2 is to evaluate the effectiveness of a 6-day course of daily prednisolone therapy during an URTI in reducing the development of a subsequent relapse in a developed nation.METHODS/DESIGN: The subjects will be 300 children with relapsing SSNS (≥2 relapses in preceding year), who will be randomised to receive either a 6-day course of daily prednisolone or no change to their current therapy (with the use of placebo to double blind) each time they develop an URTI over 12 months. A strict definition for URTI will be used. Subjects will be reviewed at 3, 6, 9 and 12 months to capture data regarding relapse history, ongoing therapy and adverse effect profile, including behavioural problems and quality of life. A formal health economic analysis will also be performed. The primary end point of the study will be the incidence of URTI-related relapse (3 days of Albustix +++) following the first infection during the 12-month follow-up period. DNA and RNA samples will be collected to identify a potential genetic cause for the disease. Subjects will be recruited from over 100 UK centres with the assistance of the Medicines for Children Research Network. PREDNOS 2 is funded by the National Institute for Health Research Health Technology Assessment Programme (11/129/261).DISCUSSION: We propose that PREDNOS 2 will be a pivotal study that will inform the future standard of care for children with SSNS. If it is possible to reduce the disease relapse rate effectively and safely, this will reduce the morbidity and cost associated with drug treatment, notwithstanding hospital admission and parental absence from employment.TRIAL REGISTRATION: Current Controlled Trials (ISRCTN10900733).</p

Use of an electronic patient-reported outcome measure in the management of patients with advanced chronic kidney disease:the RePROM pilot trial protocol

INTRODUCTION Chronic kidney disease (CKD) affects up to 16% of adults in the UK. Patient quality of life is particularly reduced in end-stage renal disease and is strongly associated with increased hospitalisation and mortality. Thus, accurate and responsive healthcare is a key priority. Electronic patient-reported outcome measures (ePROMs) are online questionnaires which ask patients to self-rate their health status. Evidence in oncology suggests that the use of ePROM data within routine care, alongside clinical information, may enhance symptom management and improve patient outcomes. However, National Health Service (NHS)-based ePROM research in CKD is lacking. This pilot trial will assess the feasibility of undertaking a full-scale randomised controlled trial (RCT) in patients with CKD within the NHS. METHODS AND ANALYSIS The renal ePROM pilot trial is an investigator-led single-centre, open-label, two-arm randomised controlled pilot trial of 66 participants ≥18 years with advanced CKD. Participants will be randomised to receive either usual care or usual care supplemented with an ePROM intervention. Participants within the intervention arm will be asked to submit monthly self-reports of their health status using the ePROM system. The system will provide tailored information to patients in response to each report and notify the clinical team of patient deterioration. The renal clinical team will monitor for ePROM notifications and will respond with appropriate action, in line with standard clinical practice. Measures of study feasibility, participant quality of life and CKD severity will be completed at 3 monthly intervals. Health economic outcomes will be assessed. Clinicians will record treatment decision-making. Acceptability and feasibility of the protocol will be assessed alongside outcome measure and intervention compliance rates. Qualitative process evaluation will be conducted. ETHICS AND DISSEMINATION The findings will inform the design of a full-scale RCT and the results will be submitted for publication in peer-reviewed journals. The study has ethical approval. TRIAL REGISTRATION NUMBERS ISRCTN12669006; Pre-results

Sixteen-week versus standard eight-week prednisolone therapy for childhood nephrotic syndrome: the PREDNOS RCT.

BackgroundThe optimal corticosteroid regimen for treating the presenting episode of steroid-sensitive nephrotic syndrome (SSNS) remains uncertain. Most UK centres use an 8-week regimen, despite previous systematic reviews indicating that longer regimens reduce the risk of relapse and frequently relapsing nephrotic syndrome (FRNS).ObjectivesThe primary objective was to determine whether or not an extended 16-week course of prednisolone increases the time to first relapse. The secondary objectives were to compare the relapse rate, FRNS and steroid-dependent nephrotic syndrome (SDNS) rates, requirement for alternative immunosuppressive agents and corticosteroid-related adverse events (AEs), including adverse behaviour and costs.DesignRandomised double-blind parallel-group placebo-controlled trial, including a cost-effectiveness analysis.SettingOne hundred and twenty-five UK paediatric departments.ParticipantsTwo hundred and thirty-seven children presenting with a first episode of SSNS. Participants aged between 1 and 15 years were randomised (1 : 1) according to a minimisation algorithm to ensure balance of ethnicity (South Asian, white or other) and age (≤ 5 or ≥ 6 years).InterventionsThe control group (n = 118) received standard course (SC) prednisolone therapy: 60 mg/m2/day of prednisolone in weeks 1-4, 40 mg/m2 of prednisolone on alternate days in weeks 5-8 and matching placebo on alternate days in weeks 9-18 (total 2240 mg/m2). The intervention group (n = 119) received extended course (EC) prednisolone therapy: 60 mg/m2/day of prednisolone in weeks 1-4; started at 60 mg/m2 of prednisolone on alternate days in weeks 5-16, tapering by 10 mg/m2 every 2 weeks (total 3150 mg/m2).Main outcome measuresThe primary outcome measure was time to first relapse [Albustix® (Siemens Healthcare Limited, Frimley, UK)-positive proteinuria +++ or greater for 3 consecutive days or the presence of generalised oedema plus +++ proteinuria]. The secondary outcome measures were relapse rate, incidence of FRNS and SDNS, other immunosuppressive therapy use, rates of serious adverse events (SAEs) and AEs and the incidence of behavioural change [using Achenbach Child Behaviour Checklist (ACBC)]. A comprehensive cost-effectiveness analysis was performed. The analysis was by intention to treat. Participants were followed for a minimum of 24 months.ResultsThere was no significant difference in time to first relapse between the SC and EC groups (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17; log-rank p = 0.3). There were also no differences in the incidence of FRNS (SC 50% vs. EC 53%; p = 0.7), SDNS (44% vs. 42%; p = 0.8) or requirement for other immunosuppressive therapy (56% vs. 54%; p = 0.8). The total prednisolone dose received following completion of study medication was 5475 mg vs. 6674 mg (p = 0.07). SAE rates were not significantly different (25% vs. 17%; p = 0.1) and neither were AEs, except poor behaviour (yes/no), which was less frequent with EC treatment. There were no differences in ACBC scores. EC therapy was associated with a mean increase in generic health benefit [0.0162 additional quality-adjusted life-years (QALYs)] and cost savings (£4369 vs. £2696).LimitationsStudy drug formulation may have prevented some younger children who were unable to swallow whole or crushed tablets from participating.ConclusionsThis trial has not shown any clinical benefit for EC prednisolone therapy in UK children. The cost-effectiveness analysis suggested that EC therapy may be cheaper, with the possibility of a small QALY benefit.Future workStudies investigating EC versus SC therapy in younger children and further cost-effectiveness analyses are warranted.Trial registrationCurrent Controlled Trials ISRCTN16645249 and EudraCT 2010-022489-29.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 26. See the NIHR Journals Library website for further project information

Resuscitation with pre-hospital blood products in adults with trauma-related haemorrhagic shock:the RePHILL RCT

Background: The treatment of traumatic haemorrhagic shock has been transformed through better haemorrhage control, use of tranexamic acid and use of blood products. The improved survival seen from these strategies has stimulated an interest in pre-hospital transfusion.Objectives: To determine if the clinical effectiveness of resuscitation with red blood cells and lyophilised plasma was superior to 0.9% saline for improving tissue perfusion and reducing mortality in adults with haemorrhagic shock following major trauma.Design: A multi-centre, allocation concealed, open-label, parallel group, randomised controlled trial (with internal pilot).Setting: The trial was conducted in four civilian pre-hospital critical care services who operated within the National Health Service (NHS) England Major Trauma Networks.Participants: Adults (aged ≥16 years) who had sustained traumatic injuries, were attended by a pre-hospital emergency medical team and were hypotensive (systolic blood pressure &lt;90 mmHg or absence of radial pulse) as a consequence of traumatic haemorrhage were eligible for inclusion. The exclusion criteria were known or apparently &lt;16 years, blood administered on scene prior to the arrival of the RePHILL team, traumatic cardiac arrest where (1) the arrest occurred prior to arrival of the team and/or (2) the primary cause is not hypovolaemia, refusal of blood product administration, known Jehovah’s Witness, pregnancy, isolated head injury without evidence of external haemorrhage, prisoners in the custody of HM Prison and Probation Service.Interventions: Participants were randomised to receive up to either two units each of red blood cells and lyophilised plasma or up to 1 L 0.9% saline. Treatment was administered through the intravenous or intraosseous route.Main outcome measures: The primary outcome was a composite of episode mortality and/or impaired lactate clearance. The secondary outcomes included the individual components of the primary outcome.Results: From 6 December 2016 to 2 January 2021, pre-hospital medical teams randomised 432 participants to red blood cell/lyophilised plasma (n = 209) or 0.9% saline (n = 223) out of a target sample size of 490. Most participants were white (62%), males (82%), median age 38 (interquartile range 26 to 58), involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, interquartile range 25 to 50). Prior to randomisation participants had received on average 430 ml crystalloid fluids and tranexamic acid (90%). The primary outcome occurred in 128/199 (64.3%) of participants randomised to red blood cell/lyophilised plasma and 136/210 (64.8%) randomised to 0.9% saline [adjusted risk difference –0.025% (95% confidence interval –9.0% to 9.0%), p = 0.996]. The event rates for the individual components of the primary outcome, episode mortality and lactate clearance were not statistically different between groups [adjusted average differences −3% (−12% to 7%); p = 0.57 and −5% (−14% to 5%), p = 0.33, respectively].Limitations: Recruitment stopped prematurely due to disruption caused by the COVID-19 pandemic.Future work: Identify the characteristics of patients who may benefit from pre-hospital blood products and whether alternative transfusion regimens are superior to standard care.Conclusions: The trial did not demonstrate that pre-hospital red blood cell/lyophilised plasma resuscitation was superior to 0.9% saline for trauma-related haemorrhagic shock.Trial registration: This trial is registered as ISRCTN62326938.Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 14/152/14) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 2. See the NIHR Funding and Awards website for further award information.<br/

Bilateral Remote Ischemic Conditioning in Children:a two-center, double-blind, randomized controlled trial in young children undergoing cardiac surgery

Objective: The study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis.Methods: We performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants.Results: Between October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 μg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 μg/L/h, n = 58) (mean difference, 13.2 μg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups.Conclusions: Bilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery

Challenges and considerations of applying nature-based solutions in low- and middle-income countries in Southeast and East Asia

Low- and middle-income countries in Southeast and East Asia face a range of challenges related to the rapid pace of urbanisation in the region, the scale of pollution, climate change, loss of ecosystem services and associated difficulties for ecological restoration. Possible pathways towards a more sustainable future lie in the applications of nature-based solutions (NBS). However, there is relatively little literature on the application of NBS in the region, particularly Southeast Asia. In this paper we address this gap by assessing the socio-ecological challenges to the application of NBS in the region – one of the most globally biodiverse. We first provide an overview and background on NBS and its underpinnings in biodiversity and ecosystem services. We then present a typology describing five unique challenges for the application of NBS in the region: (1) Characteristics of urbanisation; (2) Biophysical environmental and climatic context; (3) Environmental risks and challenges for restoration; (4) Human nature relationships and conflicts; and (5) Policy and governance context. Exploiting the opportunities through South-South and North-South collaboration to address the challenges of NBS in Southeast and East Asia needs to be a priority for government, planners and academics.Peer reviewe

Snacktivity™ to promote physical activity and reduce future risk of disease in the population: protocol for a feasibility randomised controlled trial and nested qualitative study

Background: Many people do not regularly participate in physical activity, which may negatively impact their health. Current physical activity guidelines are focused on promoting weekly accumulation of at least 150 min of moderate to vigorous intensity physical activity (MVPA). Whilst revised guidance now recognises the importance of making small changes to physical activity behaviour, guidance still focuses on adults needing to achieve at least 150 min of MVPA per week. An alternative ‘whole day’ approach that could motivate the public to be more physically active, is a concept called Snacktivity™. Instead of focusing on achieving 150 min per week of physical activity, for example 30 min of MVPA over 5 days, Snacktivity™ encourages the public to achieve this through small, but frequent, 2–5 min ‘snacks’ of MVPA throughout the whole day. Methods: The primary aim is to undertake a feasibility trial with nested qualitative interviews to assess the feasibility and acceptability of the Snacktivity™ intervention to inform the design of a subsequent phase III randomised trial. A two-arm randomised controlled feasibility trial aiming to recruit 80 inactive adults will be conducted. Recruitment will be from health and community settings and social media. Participants will be individually randomised (1:1 ratio) to receive either the Snacktivity™ intervention or usual care. The intervention will last 12 weeks with assessment of outcomes completed before and after the intervention in all participants. We are interested in whether the Snacktivity™ trial is appealing to participants (assessed by the recruitment rate) and if the Snacktivity™ intervention and trial methods are acceptable to participants (assessed by Snacktivity™/physical activity adherence and retention rates). The intervention will be delivered by health care providers within health care consultations or by researchers. Participants’ experiences of the trial and intervention, and health care providers’ views of delivering the intervention within health consultations will be explored. Discussion: The development of physical activity interventions that can be delivered at scale are needed. The findings from this study will inform the viability and design of a phase III trial to assess the effectiveness and cost-effectiveness of Snacktivity™ to increase physical activity. Trial registration: ISRCTN: 64851242