Plain English Summary
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
Trial website
Contact information
Type
Scientific
Primary contact
Dr Ashok Bhalla
ORCID ID
http://orcid.org/0000-0003-2723-9321
Contact details
Royal National Hospital for Rheumatic Diseases
Bath
BA1 1RL
United Kingdom
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
BSR / Arthritis Research UK project grant (14585)
Study information
Scientific title
Clinical efficacy of oral alendronate in ankylosing spondylitis: a randomised placebo-controlled trial
Acronym
BIAS (Bisphosphonates in Anklyosing Spondylitis)
Study hypothesis
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
1. Trent MREC, 10/05/2004, REC ref: 04/4/023
2. Site-specific approval was obtained from the all UK recruiting centres
Study design
Double-blind randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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
Phase
Phase I
Drug names
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 trial start date
01/05/2004
Overall trial end date
30/08/2010
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
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.
Participant 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)
Recruitment start date
01/05/2005
Recruitment end date
28/02/2009
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Royal National Hospital for Rheumatic Diseases
Upper Borough Walls
Bath
BA1 1RL
United Kingdom
Funders
Funder type
Charity
Funder name
Arthritis Research UK (BSR/Arthritis Research UK Project Grant (14585))
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Funder name
National Ankylosing Spondylitis Society
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
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.
Intention to publish date
Participant level data
Available on request
Basic results (scientific)
Publication list
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28079501