Clinical trial NCT02313727: Combined Treatment With TNF Inhibitor and Pamidronate in AS Patients: Effect on the Radiographic Progression
Official title: Combined Treatment With TNF (Tumor Necrosis Factor) Inhibitor and Pamidronate in AS Patients: Effect on the Radiographic Progression
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Ankylosing Spondylitis
Lead sponsor: Bnai Zion Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: Janssen-Cilag Ltd.
First posted: 2014-12-10
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: It will be a pilot, 2 year, prospective, randomized, double-blind, placebo-controlled (for pamidronate) study. All patients with AS will receive treatment with TNF inhibitor, while randomization will be performed for pamidronate versus placebo group. Primary outcome will be the rate of radiographic progression of AS, calculated after 24 months of combined treatment.

Detailed description: It will be a pilot, 2 year, prospective, randomized, double-blind, placebo-controlled (for pamidronate) study. All patients with AS will receive treatment with tumor necrosis factor (TNF) inhibitor, as indicated by local guidelines. Randomization will be performed for pamidronate vs placebo group. Pamidronate will be prescribed as monthly intravenous infusion in the dose of 60 mg/month for the first 6 consecutive months of every study year. Primary outcome will be the rate of radiographic progression of ankylosing spondylitis (AS), calculated after 24 months of combined treatment. Clinical and laboratory disease parameters will serve as secondary outcomes. These outcomes as well as safety assessments will be performed on a monthly basis up to 24 months.

Eligibility criteria: Inclusion Criteria:

* presence of spinal syndesmophytes
* normal renal and liver function
* eligibility to receive anti-TNF treatment according to local guidelines

Exclusion Criteria:

* unwilling to sigh the informed consent
* presence of significant systemic or organ-limited disorders, other than AS
* any contraindication for anti-TNF or pamidronate treatment
* presence of acute dental/periodontal disease

Primary outcomes:
measure: modified stock ankylosing spondylitis spine (mSASS) score
timeFrame: 24 months
measure: Bath ankylosing spondylitis radiographic index (BASRI)
timeFrame: 24 months
Secondary outcomes:
measure: Bath ankylosing spondylitis disease activity index (BASDAI)
timeFrame: monthly from the date of randomization up to 24 months
measure: Ankylosing spondylitis disease activity index (ASDAS)
timeFrame: monthly from the date of randomization up to 24 months
measure: Bath ankylosing spondylitis functional index (BASFI)
timeFrame: monthly from the date of randomization up to 24 months
measure: Bath ankylosing spondylitis metrology index (BASMI)
timeFrame: monthly from the date of randomization up to 24 months
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
Study officials:
References:
citation: Slobodin G, Rosner I, Feld J, Rimar D, Rozenbaum M, Boulman N, Odeh M. Pamidronate treatment in rheumatology practice: a comprehensive review. Clin Rheumatol. 2009 Dec;28(12):1359-64. doi: 10.1007/s10067-009-1256-2. Epub 2009 Aug 19.
citation: Slobodin G, Rosner I, Rimar D, Boulman N, Rozenbaum M, Odeh M. The synergistic efficacy of adalimumab and pamidronate in a patient with ankylosing spondylitis. Clin Rheumatol. 2010 Jul;29(7):793-4. doi: 10.1007/s10067-010-1378-6. Epub 2010 Jan 29.
citation: Pederson L, Ruan M, Westendorf JJ, Khosla S, Oursler MJ. Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate. Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20764-9. doi: 10.1073/pnas.0805133106. Epub 2008 Dec 15.