Alendronate in ankylosing spondylitis trial
| ISRCTN | ISRCTN12308164 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12308164 |
| Secondary identifying numbers | BSR / Arthritis Research UK project grant (14585) |
- Submission date
- 02/12/2015
- Registration date
- 15/12/2015
- Last edited
- 13/01/2017
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Plain English summary of protocol
Background and study aims
Ankylosing spondylitis (AS) is a long-term condition in which the spine becomes inflamed. It is usually treated with anti-inflammatory drugs, but they do not reduce the rate of disease progression. Patients with AS have reduced bone density of the spine and hip and are at increased risk of fractures of the spine. Such microfractures may be responsible for pain in AS. Studies using a drug called pamidronate, which belongs to a group of drugs know as bisphosphonates, given into a vein have suggested these drugs may improve the clinical features of AS. An oral form of a bisphosphonate, called alendronate, is used to treat osteoporosis. The aim of this study is to see if alendronate improves outcomes in patients with AS over a 2 year period when compared to a placebo (dummy drug).
Who can participate?
Patients aged over 21 with AS.
What does the study involve?
Participants are randomly allocated to be treated weekly with either oral alendronate or a placebo (dummy drug). We then study the disease outcome and the effects on bone density.
What are the possible benefits and risks of participating?
Alendronate may improve disease activity in AS. The risks are possible upper gastrointestinal (digestive system) side effects, arthralgia (joint pain), and rare complications of osteonecrosis (bone disease) of the jaw.
Where is the study run from?
Royal National Hospital for Rheumatic Diseases (UK).
When is the study starting and how long is it expected to run for?
May 2004 to August 2010.
Who is funding the study?
Arthritis Research UK and the National Ankylosing Spondylitis Society.
Who is the main contact?
Dr Ashok Bhalla
Contact information
Scientific
Royal National Hospital for Rheumatic Diseases
Bath
BA1 1RL
United Kingdom
 ORCID ID |
0000-0003-2723-9321 |
|---|
Study information
| Study design | Double-blind randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Clinical efficacy of oral alendronate in ankylosing spondylitis: a randomised placebo-controlled trial |
| Study acronym | BIAS (Bisphosphonates in Anklyosing Spondylitis) |
| Study objectives | To investigate the potential disease modifying properties of alendronate in a population of ankylosing spondylitis (AS) patients with a spectrum of mild to severe disease activity, reflecting routine clinical practice. |
| Ethics approval(s) | 1. Trent MREC, 10/05/2004, REC ref: 04/4/023 2. Site-specific approval was obtained from the all UK recruiting centres |
| Health condition(s) or problem(s) studied | Ankylosing spondylitis |
| Intervention | Oral alendronate 70 mg weekly or placebo The total duration of treatment was 2 years and follow-up for all treatment arms was 2 years from enrolment. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Alendronic acid |
| Primary outcome measure | Bath Ankylosing Spondylitis Global score (BAS-G), assessing overall change in patient’s symptoms and general health over the preceding month. Scored at baseline, 3, 6, 12, 18 and 24 months |
| Secondary outcome measures | 1. Disease activity (Bath AS Disease Activity Index (BASDAI) scored at baseline, 3, 6, 12, 18 and 24 months 2. Physical function (Bath AS Functional Index (BASFI) scored at baseline, 3, 6, 12, 18 and 24 months 3. Mobility (Bath AS Metrology Index (BASMI) measured at baseline and 24 months 4. Laboratory measurements: 4.1. At baseline and 6 months blood was taken for measurement of cytokines and metalloproteinases 4.2. The inflammation marker, CRP, was measured at baseline, 3, 6, 12 and 24 months 5. Radiographic features were assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and Bath AS Radiology Index (BASRI) at 0 and 24 months 6. Assessment in SpondyloArthritis international Society (ASAS) 20 and ASAS40 at 0 and 24 months |
| Overall study start date | 01/05/2004 |
| Completion date | 30/08/2010 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | The study was powered to detect a minimal clinically important difference of 1.5 in the primary outcome measure (BAS-G). With 95% power to reach 5% level of significance this required a total sample size of 140 (70 in each group). Assuming a 20% dropout rate, 90 patients were required in each group to obtain a sample size of 70. |
| Key inclusion criteria | 1. Patients had to meet the modified New York criteria for the diagnosis of AS, which we refined to allow for MRI diagnosis of sacroiliitis, and a requirement for a minimum pre-defined movement restriction 2. Fulfil ASAS criteria for axial SpA 3. Aged over 21 years 4. If taking NSAID, have been on a stable dose for at least 4 weeks 5. There was no minimal level of disease activity required for entry to the study |
| Key exclusion criteria | 1. Any intervention or underlying disease with the potential to effect disease activity or bone density, including treatment with anti-TNF 2. Patients with bilateral hip replacements or previous back surgery that would prevent accurate bone density measurement by dual x-ray absorptiometry (DXA) |
| Date of first enrolment | 01/05/2005 |
| Date of final enrolment | 28/02/2009 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Bath
BA1 1RL
United Kingdom
Sponsor information
Hospital/treatment centre
Upper Borough Walls
Bath
BA1 1RL
England
United Kingdom
"ROR" |
https://ror.org/05va5gy74 |
|---|
Funders
Funder type
Charity
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The plans were to present results at national meeting of the British Society for Rheumatology (BSR) and publish in peer-reviewed journal. |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/05/2017 | Yes | No |
Editorial Notes
13/01/2017: Publication reference added.
