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

• ClinicalTrials.gov Identifier: NCT04115397
• Recruitment Status: Not yet recruiting
• First Posted: October 4, 2019
• Last Update Posted: October 4, 2019
• Sponsor: Karolinska Institutet
• Information provided by (Responsible Party): Anca Catrina, Karolinska Institutet

Study Description

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.

Study Design

• 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

Arms and Interventions

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; Placebo

Outcome Measures

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Anca Catrina, MD, PhD, Professor, Karolinska Institutet
• ClinicalTrials.gov Identifier: NCT04115397
• Other Study ID Numbers: 2018/682-31
• First Posted: October 4, 2019
• Last Update Posted: October 4, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

Zoledronic Acid; Bone Density Conservation Agents; Physiological Effects of Drugs