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Bisphosphonates for the Treatment of Seropositive Musculoskeletal Complaints (PREVENT RA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04115397
Recruitment Status : Not yet recruiting
First Posted : October 4, 2019
Last Update Posted : October 4, 2019
Information provided by (Responsible Party):
Anca Catrina, Karolinska Institutet

Brief Summary:

Seropositive Rheumatoid arthritis (RA) is characterized by autoantibodies that develop prior to clinical onset, allowing identification of individuals at risk for disease development. In a unique program in Stockholm, seropositive individuals presenting with musculoskeletal complains are currently identified and followed-up in a dedicated outpatient clinical program. Despite significant disease burden and increased sick leave among these individuals, we lack today any therapeutic and preventive measures.

We aim to (1). establish a nation-wide health program, (2). develop an algorithm for disease risk estimation and (3). test a novel strategy to delay and/or prevent disease onset in seropositive at risk individuals with musculoskeletal complains. We will perform a multicentre randomised study to treat autoantibody-positive individuals at risk for developing RA presenting with pain (Population), by repurposing of bisphosphonates (Intervention) as compared to placebo (Control) to treat pain (primary Outcome) and delay/prevent RA development during 1-year follow-up (secondary Outcome)

Condition or disease Intervention/treatment Phase
Seropositive Muskuloskeletal Complaints Drug: Zoledronic Acid Drug: Placebo Phase 4

Detailed Description:

we have recently identified a novel disease-triggering pathogenic mechanism in autoantibody-positive individuals consisting in a bone-mediated induction of pain by autoantibodies. We hypothesize that specific targeting of this new mechanism, rather than using therapies developed for already established disease (where other mechanisms are active), will be able to treat pain with arthralgia and halt disease progression in seropositive at-risk individuals.

We will address this hypothesis by repurposing of bisphosphonates, currently used in clinical practice in both RA patients as well as in many individuals at risk for RA (mainly women in post-menopausal age). We will perform a multi centre, prospective, randomised, double-blind and placebo-controlled study with 2 parallel groups.

Patients will be randomised 1:1 to receive either one infusion aclasta (5 mg zolendronic acid, n=40) or placebo (n=40). The primary outcome is the VAS pain score and the study is powered to detect a 20% difference in the primary endpoint between the active and the control arm. The study is powered to detect a 20-percentage point difference in proportions between the control and the treated group. Subjects may withdraw from the trial at any time at their own or the investigators request for safety reasons.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Towards Efficient Prediction and Prevention of Rheumatoid Arthritis
Estimated Study Start Date : January 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Bisphophonate
Zolendronic acid, one infusion iv
Drug: Zoledronic Acid
Treating seropositive individuals with musculoskeletal symptoms with one infusion zolendronic acid as compared to placebo

Placebo Comparator: Placebo
Placebo, one infusion iv
Drug: Placebo

Primary Outcome Measures :
  1. VAS pain [ Time Frame: 3 months ]
    PAin on a visual analogue scale

Secondary Outcome Measures :
  1. HAQ [ Time Frame: 3 months ]
    Health assessment questionnaire

  2. MRI [ Time Frame: 6 months ]
    MRI investigation of the symptomatic joints in the hands

  3. Rheumatoid Arthritis (RA ) diagnosis [ Time Frame: 1 year ]
    Getting a diagnosis of RA

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Age older than 18 years Lack of arthritis as estimated by clinical and ultrasound examination of the joints ACPA positive Intermediate or high risk for RA (according to the algorithm described above) VAS score of at least 20 mm

Exclusion Criteria:

A previous diagnosis of arthritis Intolerance/contraindication to any of the study medications

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Responsible Party: Anca Catrina, MD, PhD, Professor, Karolinska Institutet Identifier: NCT04115397    
Other Study ID Numbers: 2018/682-31
First Posted: October 4, 2019    Key Record Dates
Last Update Posted: October 4, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Zoledronic Acid
Bone Density Conservation Agents
Physiological Effects of Drugs