Fatigue in Lupus Intervention Programmes (FLIP)

Official title

Fatigue in Lupus Intervention Programmes (FLIP): A Randomised Controlled Trial Investigating the Effectiveness of Fatigue Management in Systemic Lupus Erythematosus

Overview

Systemic Lupus Erythematosus (SLE) is an autoimmune rheumatic disease. Patients report that fatigue has a significant impact on their quality of life but is often not discussed in healthcare settings. Fatigue is more prevalent in SLE than other Rheumatic diseases. Management across the NHS is very variable ranging from a booklet to one to one appointments or, less often, a group intervention. Previous studies in other Rheumatic diseases have shown that a group cognitive behavioural approach can be effective in helping patients manage their fatigue. The COVID-19 pandemic changed the way healthcare is delivered in the NHS . Healthcare professionals had to find alternate solutions e.g. Virtual appointments. Our study aims to establish whether a virtual group Fatigue Management Programme and a fatigue booklet (Versus Arthritis and Lupus UK) is more effective at reducing the impact of fatigue in SLE participants than the fatigue booklet alone. The investigators will also compare a shortened 4-week to the standard 7-week programme to lessen the time commitment for participants and potentially reduce waiting times.The investigators will measure the effectiveness of the interventions through the use of Patient Reported Outcome Measures (PROMs) at several intervals whilst the participant is enrolled in the study.The pilot study will run in a single site in Edinburgh. The investigators aim to find a manageable, cost effective solution for the NHS and patients to address this frequently unmet need.

Detailed description

The FLIP study will recruit SLE patients to a single centre, three arm randomised controlled trial which will compare standard care ( fatigue booklets available in all Rheumatology departments in the UK or online ) with live online fatigue management groups for effectiveness at managing fatigue.

Lupus UK will advertise the study through their website, newsletter and social media. Participants can be identified and enrolled to the study in three ways:

1. The participant can be identified by any member of the Rheumatology department in NHS Lothian through participant routine Rheumatology appointment or local database. No patient records will be screened . 2. Participants can be identified through the Scottish Lupus Registry Database as they will have already consented to being contacted about research. 3. Participants can also self-enrol to the study through the link to the FLIP website from Lupus UK .

Posters, leaflets and LUPUS UK communications will have a link and QR code which will take interested participants to the patient information sheet to read about the study.They can contact the study team with any questions before proceeding to accessing the enrolment process in the REDCap secure server. The central study team or the participant themselves can confirm their eligibility by completing short screening questions.The study team can also help the patient with any questions regarding the online consent form if necessary. If the participant is eligible and wishes to proceed they will be asked to complete an online consent and be assigned a unique identification code number (UICN).

After the participant has consented online in REDCap and completed personal details/demographics and baseline PROMs questionnaires they will be randomised to either standard care, standard care plus 4 week programme or standard care plus 7 week programme. The ratio of randomisation will be 1.1.1 .

Participants will complete the same PROMS three more times after the baseline: on completion of the intervention, at 6 months and at 12 months.

The PROMs will be

1. Modified Fatigue Impact Score (MFIS) 2. SLE quality of life questionnaire (LupusQoL) 3. Pittsburgh Sleep quality Inventory ( PSQI) 4. Visual Analog scale of fatigue impact ( FI-VAS) 5. Participant health questionnaire -4 item (PHQ4) 6. Self -Efficacy for managing chronic disease 6 item scale (SEMCD-6) 7. Quick Systemic Lupus Activity Questionnaire (Q-SLAQ)

If a participant has access to a Systemic Lupus Erythematosus Disease Activity Index ( SLEDAI) score this may be included .

Participants will also be asked to complete a satisfaction questionnaire after the intervention completion.

The end of study is defined as the last data collection at 52 weeks from the last participant after group intervention or standard care whichever comes last.

The trial team will analyse the qualitative data from participants. A health economist will calculate the NHS utilisation / economic evaluation by mapping the LUPUSQoL to the Short Form 6 dimension (SF6D) to obtain quality adjusted life years (QALYs) .

A statistician will analyse the data from the PROMs with standard statistical software in R and report descriptive statistics such as means, medians, standard deviations and standard errors of the variables measured. Statistical significance will be measured for the aims of the study using unmatched and paired T- tests.

The primary outcome of our study, MFIS measurements, will be assessed using linear regression models including a random effect to account for grouping by centre. The investigators will assess whether the treatment outcome is maintained by analysing longitudinal data collected over 1 year using linear mixed-effect models with a suitable covariance structure. The secondary outcomes will be analysed in an analogous way. The investigators will also analyse how the secondary outcomes covary with the MFIS scores. The investigators will handle non-compliance by analysing the data according to intention-to-treat principles. In the unlikely event of unused data arising, the investigators will include these in suitable subgroup analyses. Spurious data will be followed up with patients and will only be excluded from the study as a measure of last resort. The investigators are not planning to carry out interim analyses nor to terminate the study early.

The results will be published in peer reviewed journals and by Lupus UK .

Interventions

• Behavioral Standard Care
  Participants receive fatigue booklets from two charitable organisations providing information on fatigue, sleep, energy conservation, exercise and stress to help manage fatigue.
• Behavioral 4 week FMP
  Participants attend 3 once weekly live online group interventions with a final intervention 8 weeks later.
• Behavioral 7 week FMP
  Participants attend 6 once weekly live online group interventions with a final intervention 8 weeks later.

Primary outcome measures

• Modified Fatigue Impact Score (MFIS) [Time frame: 12 months]

Secondary outcome measures (7)

• Lupus quality of life questionnaire (LupusQoL) [Time frame: 12 months]
• Pittsburgh Sleep quality Inventory ( PSQI) [Time frame: 12 months]
• Visual Analog scale of fatigue impact (FI-VAS) [Time frame: 12 months]
• Participant Health Questionnaire (PHQ4) [Time frame: 12 months]
• Self-Efficacy for Managing Chronic Diseases 6-item Scale [Time frame: 12 Months]
• Quick Systemic Lupus Erythematosus Activity Questionnaire (Q-SLAQ) [Time frame: 12 months]
• Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Have a confirmed SLE Diagnosis
• Be over 18 at time of consent
• Report fatigue to be a chronic problem in the last 4 weeks with a VAS fatigue impact ≥ 6, based on a scale of 1 ( no fatigue impact on quality of life ) to 10 (severe impact of fatigue on quality of life).\[20\]
• Agree to online consent, complete questionnaires and be randomised to standard care or group intervention programme via secure server (REDCap).
• Not have taken part in a group fatigue or pain management programme in the past 5 years.
• Have the ability to read and converse in English competently
• Have access to a computer/Smartphone/Tablet for internet and audio/video access.
• Be able to or willing to learn to use an NHS approved platform.
• Be willing to provide a telephone, postal address and email address for communication related to the FLIP trial.

Exclusion criteria

• They are unable to understand English sufficiently to attend a live online group programme. Facilitators and other group members will most likely only speak English.
• They are unable to provide confirmation of eligibility, complete online informed consent or questionnaires
• They are currently participating in an interventional trial

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United Kingdom · 1 center

• NHS Lothian — Edinburgh

Publications

• Ahn GE, Ramsey-Goldman R. Fatigue in systemic lupus erythematosus. Int J Clin Rheumtol. 2012 Apr 1;7(2):217-227. doi: 10.2217/IJR.12.4. PMID 22737181
• Azizoddin DR, Gandhi N, Weinberg S, Sengupta M, Nicassio PM, Jolly M. Fatigue in systemic lupus: the role of disease activity and its correlates. Lupus. 2019 Feb;28(2):163-173. doi: 10.1177/0961203318817826. Epub 2018 Dec 22. PMID 30580659
• Arnaud L, Gavand PE, Voll R, Schwarting A, Maurier F, Blaison G, Magy-Bertrand N, Pennaforte JL, Peter HH, Kieffer P, Bonnotte B, Poindron V, Fiehn C, Lorenz H, Amoura Z, Sibilia J, Martin T. Predictors of fatigue and severe fatigue in a large international cohort of patients with systemic lupus erythematosus and a systematic review of the literature. Rheumatology (Oxford). 2019 Jun 1;58(6):987-99 PMID 30597077
• Wang B, Gladman DD, Urowitz MB. Fatigue in lupus is not correlated with disease activity. J Rheumatol. 1998 May;25(5):892-5. PMID 9598886
• Nikiphorou E, Santos EJF, Marques A, Bohm P, Bijlsma JW, Daien CI, Esbensen BA, Ferreira RJO, Fragoulis GE, Holmes P, McBain H, Metsios GS, Moe RH, Stamm TA, de Thurah A, Zabalan C, Carmona L, Bosworth A. 2021 EULAR recommendations for the implementation of self-management strategies in patients with inflammatory arthritis. Ann Rheum Dis. 2021 Oct;80(10):1278-1285. doi: 10.1136/annrheumdis-2021-22 PMID 33962964
• Hewlett S, Almeida C, Ambler N, Blair PS, Choy E, Dures E, Hammond A, Hollingworth W, Kadir B, Kirwan J, Plummer Z, Rooke C, Thorn J, Turner N, Pollock J. Group cognitive-behavioural programme to reduce the impact of rheumatoid arthritis fatigue: the RAFT RCT with economic and qualitative evaluations. Health Technol Assess. 2019 Oct;23(57):1-130. doi: 10.3310/hta23570. PMID 31601357
• Hewlett S, Almeida C, Ambler N, Blair PS, Choy EH, Dures E, Hammond A, Hollingworth W, Kadir B, Kirwan JR, Plummer Z, Rooke C, Thorn J, Turner N, Pollock J; RAFT Study Group. Reducing arthritis fatigue impact: two-year randomised controlled trial of cognitive behavioural approaches by rheumatology teams (RAFT). Ann Rheum Dis. 2019 Apr;78(4):465-472. doi: 10.1136/annrheumdis-2018-214469. Epub 2019 PMID 30793700
• Martin KR, Bachmair EM, Aucott L, Dures E, Emsley R, Gray SR, Hewlett S, Kumar V, Lovell K, Macfarlane GJ, MacLennan G, McNamee P, Norrie J, Paul L, Ralston S, Siebert S, Wearden A, White PD, Basu N. Protocol for a multicentre randomised controlled parallel-group trial to compare the effectiveness of remotely delivered cognitive-behavioural and graded exercise interventions with usual care alone t PMID 30705244

Identifiers

NCT: NCT06308770 · AC21137

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗