Condition category
Musculoskeletal Diseases
Date applied
02/12/2015
Date assigned
15/12/2015
Last edited
15/12/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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 measures

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

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

Sponsor information

Organisation

Royal National Hospital for Rheumatic Diseases (UK)

Sponsor details

Upper Borough Walls
Bath
BA1 1RL
United Kingdom

Sponsor type

Hospital/treatment centre

Website

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes