Probiotics in Paget's disease
| ISRCTN | ISRCTN12180483 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12180483 |
| IRAS number | 303256 |
| Secondary identifying numbers | AC21099, IRAS 303256 |
- Submission date
- 25/01/2023
- Registration date
- 03/02/2023
- Last edited
- 05/12/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Musculoskeletal Diseases
Plain English Summary
Background and study aims
Epidemiological studies have shown that environmental factors influence the occurrence and severity of Paget’s disease of bone (PDB), but the identity of these factors is unclear. There is previous evidence that dietary calcium and vitamin D deficiency might predispose to PDB. The study will investigate the role of dietary calcium and vitamin D and of the microbiome as environmental factors which may modify the disease activity in PDB. The aim of this study will be to explore the effects of dietary calcium and vitamin D supplements and probiotic supplements on biochemical markers of metabolic activity in patients with mild PDB who are not considered to require treatment with bisphosphonate therapy and to study effects on pain and quality of life.
Who can participate?
Adult patients with PDB
What does the study involve?
The study involves three hospital visits at baseline, 3 months and 6 months. Participants will be allocated to a treatment group and will receive either probiotics, combined vitamin D and calcium supplements, or a placebo. Participants will give a blood sample and a stool sample at each visit and will answer questions related to their quality of life and the presence of pain.
What are the possible benefits and risks of participating?
There are no benefits to taking part in this study, but the results from this study might help to improve understanding of the causes of PDB and help in the search for new treatments. It is unlikely that taking the supplements will cause any side effects, but we will be monitoring all participants closely for any adverse effects that might occur.
Where is the study run from?
The Bone research group at the Institute of Genetics and Cancer, The University of Edinburgh (UK)
When is the study starting and how long is it expected to run for?
February 2022 to January 2026
Who is funding the study?
H2020 Excellent Science - European Research Council
Who is the main contact?
Kathryn Berg, kathryn.berg@ed.ac.uk
Contact information
Principal Investigator
Professor of Rheumatology
University of Edinburgh
Centre for Genomic and Experimental Medicine
Institute of Genetics and Molecular Medicine
Western General Hospital
Edinburgh
EH4 2XU
United Kingdom
 ORCID ID |
0000-0002-2804-7586 |
|---|---|
| Phone | +44 (0)1316518741 |
| stuart.ralston@ed.ac.uk |
Scientific
University of Edinburgh
Centre for Genomics and Experimental Medicine
Institute of Genetics and Cancer
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom
| ORCID ID |
0000-0002-5972-4009 |
|---|---|
| Phone | +44 (0)1316518755 |
| kathryn.berg@ed.ac.uk |
Public
University of Edinburgh
Centre for Genomics and Experimental Medicine
Institute of Genetics and Cancer
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom
| Phone | +44 (0)1316518755 |
|---|---|
| kathryn.berg@ed.ac.uk |
Study information
| Study design | Multicentre interventional blinded randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Home, Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Measuring the effect of probiotics or calcium/vitamin D supplements in patients with Paget's disease of bone |
| Study acronym | PRiP |
| Study hypothesis | A reduction of serum alkaline phosphatase will be observed in at least one of the active groups who are receiving a probiotic intervention plus calcium and vitamin D supplementation but not the control group who are receiving probiotics alone. |
| Ethics approval(s) | Approved 05/08/2022, West of Scotland Research Ethics Service (Ground Floor Ward 11, Dykebar Hospital, Grahamston Road, Paisley, PA2 7DE, UK; +44 (0)141 314 0212; WoSREC3@ggc.scot.nhs.uk), ref: 22/WS/0075 |
| Condition | Paget's disease of bone |
| Intervention | One arm of the study will receive a probiotic intervention. Probiotics have previously been evidenced to be beneficial to bone health. The probiotic intervention will consist of three lactobacillus strains in capsular form, to be taken once daily to provide 1 x 1010 PFU of lactobacillus per day. The preparation will be supplied by Probi (www.probi.com) and is identical to a supplement previously used in the prevention of postmenopausal bone loss in women. Participants will receive a three-month supply face-to-face at the baseline and 3-month visits and these will be dispensed by a qualified member of the local research team who will be familiar with the pharmacy manual. The probiotic capsules will be shipped by Probi under temperature-controlled conditions (4-8oc) to the coordinating centre where they will be stored in a dedicated temperature-controlled refrigerator. The product will be shipped from the co-ordinating centre to study centres on an intermittent basis under temperature-controlled conditions (4-8oc) and stored in local study centres in a temperature-controlled refrigerator. Another arm of the study will receive a combined vitamin D/calcium supplement. Both are commonly used in this patient group and are known to positively influence bone health. The supplement will be provided containing 500 mg of elemental calcium and 200 units of vitamin D taken twice daily in the form of supplements purchased from Simply Supplements. Participants will receive a three-month supply face-to-face at the baseline and 3-month visits and these will be dispensed by a qualified member of the local research team who will be familiar with the pharmacy manual. The supplements will be stored at the co-ordinating centre in a locked cabinet dedicated to the study and shipped at ambient temperature to the study centres on an intermittent basis where they will be stored at ambient temperature. The placebo arm will receive capsules containing excipients alone (maize starch) which will also be supplied by Probi and will be taken once daily. Participants will receive a three-month supply face-to-face at the baseline and 3-month visits and these will be dispensed by a qualified member of the local research team who will be familiar with the pharmacy manual. The placebo intervention will be shipped by Probi under temperature-controlled conditions (4-8oc) to the co-ordinating centre where it will be stored in a dedicated temperature-controlled refrigerator. The product will be shipped from the co-ordinating centre to study centres on an intermittent basis under temperature-controlled conditions (4-8oc) and stored in local study centres in a temperature-controlled refrigerator. Participants will be randomised using the randomisation function on REDCap which has been programmed to allocate participants to each treatment arm to ensure an even spread of interventions within each centre. |
| Intervention type | Supplement |
| Primary outcome measure | Metabolic activity of Paget's disease of the bone assessed by serum concentrations of total alkaline phosphatase measured using an alkaline phosphatase test at 6 months |
| Secondary outcome measures | 1. Biochemical markers of bone metabolism levels, including PINP, CTX, PTH and 25(OH)D, measured using blood samples collected at baseline, 3 and 6 months 2. Health-related quality of life measured using the 36-Item Short Form Survey (SF-36) at 6 months 3. Presence and severity of pain at sites affected by Paget's disease of the bone measured using a Visual Analogue Scale at baseline, 3 and 6 months 4. Microbiome measured using 16S sequence analysis of stool samples at 3 and 6 months |
| Overall study start date | 01/02/2022 |
| Overall study end date | 31/01/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 75 |
| Participant inclusion criteria | 1. Aged 18 years old and over 2. Clinical diagnosis of Paget's disease of the bone confirmed by characteristic appearances on radionuclide bone scan and /or x-ray 3. Serum total alkaline phosphatase elevated above the upper limit of normal or within the upper half of the local reference range 4. Willing and able to give informed consent |
| Participant exclusion criteria | 1. Unable or unwilling to give informed consent 2. Bisphosphonate therapy thought to be indicated for the treatment of Paget's disease of the bone on clinical grounds 3. Currently being treated with bisphosphonates, denosumab or calcitonin for any reason 4. Currently being treated with combined calcium and vitamin D supplements 5. Treatment with oral or intravenous bisphosphonates during the previous 24 months 6. Treatment with denosumab during the past 12 months 7. Treatment with calcitonin during the previous 3 months. 8. Treatment with combined calcium and vitamin D supplements during the past 4 weeks 9. Receiving probiotics during the previous 3 months |
| Recruitment start date | 16/02/2024 |
| Recruitment end date | 31/07/2025 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Edinburgh
Lothian
EH4 2XU
United Kingdom
Glasgow
G51 4TF
United Kingdom
Llandough
Penarth
CF64 2XX
United Kingdom
Prescot Street
Liverpool
L7 8XP
United Kingdom
Middlesbrough
TS4 3BW
United Kingdom
Leicester
LE1 5WW
United Kingdom
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Eccles
Salford
M6 8HD
United Kingdom
Nottingham
NG5 1PB
United Kingdom
Stanmore
HA7 4LP
United Kingdom
Sponsor information
University/education
47 Little France Crescent
Edinburgh
EH16 4TJ
Scotland
United Kingdom
| Phone | +44 (0)131 242 3330 |
|---|---|
| resgov@accord.scot | |
| Website | http://accord.scot/ |
"ROR" |
https://ror.org/01x6s1m65 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- H2020 Excellent Science - European Research Council, European Research Council, H2020 Wissenschaftsexzellenz - Für das Einzelziel 'Europäischer Forschungsrat (ERC)', H2020 Ciencia Excelente - Consejo Europeo de Investigación (CEI), H2020 Excellence Scientifique - Conseil européen de la recherche (CER), H2020 Eccellenza Scientifica - Consiglio europeo della ricerca (CER), H2020 Doskonała Baza Naukowa - Europejska Rada ds. Badań Naukowych (ERBN), EXCELLENT SCIENCE - European Research Council, WISSENSCHAFTSEXZELLENZ - Für das Einzelziel 'Europäischer Forschungsrat, CIENCIA EXCELENTE - Consejo Europeo de Investigación, EXCELLENCE SCIENTIFIQUE - Conseil européen de la recherche, ECCELLENZA SCIENTIFICA - Consiglio europeo della ricerca, DOSKONAŁA BAZA NAUKOWA - Europejska Rada ds. Badań Naukowych, ERC, CEI, CER, ERBN
Results and Publications
| Intention to publish date | 01/12/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to the rare nature of this disease and therefore the risk that a participant could be identified. Participant-level data will be held on secure servers at the Institute of Genetics and Cancer at the University of Edinburgh and will not be shared. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol file | version 6 | 12/03/2024 | 15/04/2024 | No | No |
Additional files
Editorial Notes
05/12/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 31/12/2024 to 31/07/2025.
2. The overall study end date was changed from 30/06/2025 to 31/01/2026.
3. The intention to publish date was changed from 01/12/2025 to 01/12/2026.
15/04/2024: The following changes were made to the study record:
1. Protocol uploaded.
2. The recruitment start date was changed from 01/03/2023 to 16/02/2024.
3. The recruitment end date was changed from 30/06/2024 to 31/12/2024.
4. The overall study end date was changed from 31/12/2024 to 30/06/2025.
5. The intention to publish date was changed from 01/06/2025 to 01/12/2025.
03/02/2023: Trial's existence confirmed by the West of Scotland Research Ethics Service (UK).
