Efficacy and Safety of Risedronate (Actonel), a Third Generation Bisphosphonate in Patients With Ankylosing Spondylitis: a Phase 2 Pilot Study

Study Overview
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Brief Summary
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Randomized, controlled, double-blind, multicenter phase II study comparing risedronate 35mg (ActonelR 35mg weekly tablet) versus placebo in patients with active ankylosing spondylitis (AS) treated with standard first and second-line therapies. Primary efficacy endpoint: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The time schedule for performing the BASDAI was at screening, upon inclusion (T0), then after 3, 6 and 12 months or at the time of premature withdrawal in case of drop-out. secondary endpoints: Clinical endpoints: The secondary efficacy measures were the following: Bath Ankylosing Spondylitis Functional Index (BASFI) , Bath Ankylosing Spondylitis Metrology Index (BASMI), ASAS (Assessments in Ankylosing Spondylitis) Working Group core set of domains, Spinal pain VAS, ESR, CRP and the percentage of patients achieving 20% or greater decrease in each of these parameters. These parameters were determined at T0, T3, T6, T12 or at the time of premature withdrawal in case of drop-out. The spinal pain assessed by VAS was also done at screening. DEXA: Dual Energy X-Ray-Absorptiometry (DEXA) measurements were performed in all patients upon inclusion (T0) and at the end of the study (T12). Biochemical markers: selected biochemical markers of bone metabolism were measured at T0, T3, T6 and T12 or at the time of premature withdrawal in case of drop-out using commercially available kits. Bone formation was assessed by serum bone-specific alkaline phosphatase (BAP) and osteocalcin (OC) levels using commercially available kits. Bone resorption was assessed in serum by the C-terminal telopeptide of type I collagen degradation (Crosslaps R) and urinary N-terminal telopeptide of type I collagen degradation (Osteomark R). Trial with medicinal product

Conditions
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Ankylosing Spondylitis

Intervention / Treatment
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* Drug: drug treatment


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: •Male or non-pregnant women (only women who are post menopausal, surgically sterile or practicing a reliable method of contraception may be included) aged 20 years or more Meeting the Modified New York diagnostic criteria for AS (Van der Linden S et al., 1984) Symptoms of active AS for more than 6 months prior to study entry Treated by first-line therapy (NSAIDs) for more than 6 months prior to study entry Bath AS Disease Activity Index (BASDAI) score of 4 or greater (Garrett S et al, 1994) and Spinal pain of 4 or greater on a 10-cm visual analogue scale despite maximum recommended or tolerated doses of NSAIDs given for a minimum of 1 month prior to study entry Exclusion criteria: •End-stage AS with diffuse involvement of the spine (complete ankylosis) Intraarticular corticosteroid injections or IV infusion with methylprednisolone within the past 2 months prior to study entry. Patients with IA corticosteroid injections of the sacroiliac joints within the past 9 months prior to study entry. Severe renal insufficiency: serum creatinine > 25% above the upper limit of normal (>177 umol/l) Hypocalcemia Major surgery within the past 3 months prior to study entry or planned in the ensuing 12 months Orthopaedic surgery within the last 12 months Severe infections or comorbidities, or active peptic ulcer disease Patients who received bisphosphonates in the past 12 months prior to study entry or patients having known allergies to bisphosphonates. Patients treated with anti-osteoporotic drugs (except: Calcium and Vit. D) in the past 12 months prior to study entry. Patients unable to remain in an upright position (sitting or standing) during a minimum of 30 minutes No written informed consent obtained or inability to collaborate to the study design.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: drug treatment|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BASDAI |  |  |