Plain English Summary
Background and study aims
Smouldering multiple myeloma (SMM) and monoclonal gammopathy of undetermined significance (MGUS) are premalignant plasma cell conditions that precede the cancer multiple myeloma. Treatment is not administered to SMM or MGUS due to uncertainties about the effectiveness and toxicity (side effects) of existing treatment options. Lifestyle interventions to delay progression, such as exercise, have not been tested and may be beneficial. Population data shows that risk of getting multiple myeloma is reduced by about 20% in those who lead a physically active lifestyle. It is thought that exercise does not stop the initiation of MGUS/SMM, but instead may delay the progression of MGUS/SMM to multiple myeloma. One case study has shown that SMM disease activity can be reversed with exercise. The aim of this study is to assess the feasibility and safety of a progressive, walking-based exercise programme for SMM and MGUS, and to assess the impact of exercise on SMM and MGUS disease activity.
Who can participate?
Patients aged over 18 who have SMM or MGUS
What does the study involve?
Participants’ disease activity, physical fitness and quality of life are assessed. Participants will receive a progressive exercise programme plus usual care for 16 weeks. The exercise programme is run at the Royal United Hospitals Bath NHS Foundation Trust and consists of two supervised group classes per week and one session at home. The exercise programme includes cardio, strengthening and balance exercises, and stretching, as recommended by World Health Organisation physical activity guidelines for older adults. Disease activity, physical fitness and quality of life are measured again at 17 weeks.
What are the possible benefits and risks of participating?
There are both benefits and risks to taking part in the study. Benefits include a free exercise programme, feedback on health and fitness measures, £100 cash payment for travel costs and exercise resources to keep after the study. The researchers have designed the project to have the least risk possible, although not all risk is avoidable, for example, participating in a bout of exercise temporarily increases the risk of having heart problems or getting injured. Overall however, the potential benefits of exercise outweigh the possible negative consequences of exercise.
Where is the study run from?
Royal United Hospitals Bath NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
October 2017 to December 2019
Who is funding the study?
University of Bath (UK)
Who is the main contact?
1. Dr John Campbell
J.Campbell@bath.ac.uk
2. Miss Annabelle Emery
A.R.Emery@bath.ac.uk
Study website
Contact information
Type
Scientific
Contact name
Miss Annabelle Emery
ORCID ID
http://orcid.org/0000-0001-9603-4931
Contact details
Office 4.113 1 West Building
Department for Health
University of Bath
Claverton Down
Bath
BA2 7AY
United Kingdom
+44 (0)1225 383655
a.r.emery@bath.ac.uk
Type
Scientific
Contact name
Dr John Campbell
ORCID ID
http://orcid.org/0000-0001-9989-6158
Contact details
Office 5.123 1 West Building
Department for Health
University of Bath
Claverton Down
Bath
BA2 7AY
United Kingdom
+44 (0)1225 385495
j.campbell@bath.ac.uk
Additional identifiers
EudraCT/CTIS number
IRAS number
238573
ClinicalTrials.gov number
Protocol/serial number
IRAS 238573
Study information
Scientific title
Feasibility of a progressive, walking-based exercise programme for monoclonal gammopathy of undetermined significance and smouldering multiple myeloma: a single-arm pilot trial.
Acronym
Study hypothesis
The primary aim of this trial is to evaluate the feasibility and safety of a 16-week progressive, walking-based exercise programme in patients with (i) smouldering multiple myeloma (SMM) and (ii) monoclonal gammopathy of undetermined significance (MGUS).
The secondary aim of this trial is to generate preliminary data on the effects of an exercise programme on (i) disease activity, (ii) fitness, and (iii) quality of life outcomes to inform a future, adequately powered, randomised-controlled trial.
People with SMM and MGUS are at risk of progressing to the cancer multiple myeloma in their lifetime, but care guidelines do not recommend active treatment until multiple myeloma develops. This research is investigating whether a progressive exercise programme can be used to reduce disease activity.
Ethics approval(s)
1. NHS Health Research Authority, 20/07/2018, 18/LO/1034
2. University of Bath Research Ethics Approval Committee for Health, 29/08/2018, EP 17/18 210
Study design
Pilot single-centre single-arm Phase I trial
Primary study design
Interventional
Secondary study design
Non randomised study
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Premalignant plasma cell conditions: smouldering multiple myeloma and monoclonal gammopathy of undetermined significance
Intervention
Current intervention as of 25/02/2019:
Treatment arm: 16-week progressive, walking-based exercise programme. The programme will be delivered as two supervised group classes at the Royal United Hospitals Bath NHS Foundation Trust (including treadmill walking, resistance exercise and stretching) and home-based exercises (including one moderate intensity walk and daily balance and stretching exercises) each week, plus usual care.
Previous intervention as of 13/09/2018:
Participants will be randomly allocated to either the treatment or control arm. Opaque envelopes containing group allocation will be sequenced using block randomisation into ‘Treatment Arm’ = 20 and ‘Control Arm’ = 20 (sealedenvelope.com).
Treatment arm: 16-week progressive, walking-based exercise programme. The programme will be delivered as two supervised group classes at the Royal United Hospitals Bath NHS Foundation Trust (including treadmill walking, resistance exercise and stretching) and home-based exercises (including one moderate intensity walk and daily balance and stretching exercises) each week, plus usual care.
Control arm: usual care and maintenance of baseline habitual exercise habits.
All participants will be measured at week 0 and 17.
Previous interventions:
Participants will be randomly allocated to either the treatment or control arm. Opaque envelopes containing group allocation will be sequenced using block randomisation into ‘Treatment Arm’ = 20 and ‘Control Arm’ = 20 (sealedenvelope.com).
Treatment arm: 16-week progressive, walking-based exercise programme. The programme will be delivered as two supervised group classes at the Royal United Hospitals Bath NHS Foundation Trust (including treadmill walking, resistance exercise and stretching) and home-based exercises (including one moderate intensity walk and daily balance and stretching exercises) each week, plus usual care.
Control arm: usual care and maintenance of baseline habitual exercise habits, with the option to undertake the exercise programme for 16 weeks after completing their trial period in the control group.
All participants will be measured at week 0 and 17.
Intervention type
Behavioural
Primary outcome measure
1. Uptake, measured at week 0 prior to trial period:
1.1. Recruitment rate - the proportion of patients approached who are screened
1.2. Screen-pass rate - the proportion of patients who attend screening that are deemed eligible
1.3. Randomisation rate - the proportion of patients that are randomised
2. Adherence: the proportion of prescribed sessions that are performed, measured in weeks 1-16 in the treatment arm only
3. Compliance: the exercise prescribed vs. exercise completed, measured at weeks 1-16 in the treatment arm only
4. Retention: the proportion of participants who complete both baseline and follow-up measures, measured in week 17
5. Safety: the incidence and severity of adverse events, measured at weeks 0-17
Secondary outcome measures
1. Disease activity of SMM and MGUS, measured in week 0 and week 17
2. Physical fitness, measured by cardiopulmonary exercise test in week 0 and week 17
3. Physical activity level, measured by armband activity monitor in week 0 and week 16
4. Body composition, measured by dual-energy x-ray absorptiometry in week 0 and week 17
5. Quality of life, measured by questionnaires (quality of life, sleep, fatigue, frailty) in week 0 and week 17
6. Resting heart rate and blood pressure, measured in week 0 and week 17
7. CRAB indices (calcium, renal function, anaemia, bone health), measured in week 0 and week 17
8. Mechanistic measures (immune, inflammatory and metabolic biomarkers), measured in blood, saliva and urine sampled in week 0 and week 17
Overall study start date
02/10/2017
Overall study end date
02/03/2020
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Diagnostic criteria:
1.1. SMM. Defined by IMWG criteria as absence of MM defining events or amyloidosis, AND either: (i) serum monoclonal protein (IgG or IgA) >30 g/L OR urinary monoclonal protein >500 mg per 24 h, AND/OR (ii) clonal bone marrow plasma cells 10-60%. People with SMM, given their higher risk of progressing to MM, will initially be prioritised for enrollment into the trial, followed by people with MGUS, described next
OR
1.2. MGUS. Defined by IMWG criteria as absence of end-organ damage attributable to the plasma cell proliferative disorder (such as hypercalcaemia, renal insufficiency, anaemia, and bone lesions [CRAB]), or amyloidosis AND BMPC <10% AND serum M-protein <30 g/L
2. Age >18 years (adults and seniors)
Participant type(s)
Patient
Age group
Other
Lower age limit
18 Years
Sex
Both
Target number of participants
20
Total final enrolment
20
Participant exclusion criteria
1. World Health Organisation (WHO) performance status >1
2. Pregnancy
3. Deemed unsafe to exercise according to the Physical Activity Readiness Questionnaire
4. Any comorbidity that is likely to progress or be exacerbated over the course of the trial period
5. Cognitive impairment deemed a risk by the healthcare team for participation in the trial
6. Unable to understand explanations and/or provide informed consent
7. Any condition and/or behaviour that would pose undue personal risk or introduce bias into the trial
Recruitment start date
10/09/2018
Recruitment end date
15/11/2019
Locations
Countries of recruitment
England, United Kingdom
Study participating centre
Royal United Hospitals Bath NHS Foundation Trust
Combe Park
Bath
BA1 3NG
United Kingdom
Sponsor information
Organisation
University of Bath
Sponsor details
Vice-Chancellor's Office
University of Bath
Claverton Down
Bath
BA2 7AY
England
United Kingdom
Sponsor type
University/education
Website
ROR
Funders
Funder type
University/education
Funder name
University of Bath
Alternative name(s)
UniofBath
Funding Body Type
private sector organisation
Funding Body Subtype
Universities (academic only)
Location
United Kingdom
Results and Publications
Publication and dissemination plan
The trial protocol has now been made available online via the University Research Portal (https://researchportal.bath.ac.uk/en/projects/feasibility-of-a-progressive-walking-based-exercise-programme-for). A protocol paper will also be published in an academic journal (aiming for BMJ Open), estimated timeline is 6-12 months following the start of data collection. The results of the trial will be disseminated in relevant clinical, academic and patient conferences and meetings. The results will also be written up as paper publications and submitted to scientific, peer-reviewed journals.
Intention to publish date
31/07/2022
Individual participant data (IPD) sharing plan
De-identified individual participant data will be made available after publication to those who submit a research proposal that is approved by the Chief Investigator, Dr John Campbell (J.Campbell@bath.ac.uk). Data underlying the publication will be made available from the date of publication for 10 years, at which point it will be destroyed as stated in the University of Bath research data policy. The data will be held in the University of Bath Data Archive.
IPD sharing plan summary
Available on request
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 01/07/2021 | 01/07/2021 | No | No | |
| Protocol file | version 3.1 | 19/12/2018 | 18/08/2022 | No | No |
| HRA research summary | 26/07/2023 | No | No | ||
| Results article | 05/02/2024 | 06/02/2024 | Yes | No |
Additional files
- ISRCTN65527208_BasicResults_01July21.pdf Uploaded 01/07/2021
- 35215 protocol_19Dec18_v3.1.pdf