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Summary

for people ages 18 years and up (full criteria)
healthy people welcome
at San Francisco, California and other locations
study started
estimated completion:

Description

Summary

The purpose of this study is to determine if hydroxychloroquine (HCQ) is safe and effective for the prevention of future onset of rheumatoid arthritis (RA) in individuals who have elevations of an autoantibody, anti-cyclic citrullinated peptide (anti-CCP). The following recruitment strategies will be employed towards identifying healthy subjects with elevated anti-cyclic citrullinated peptide 3 (anti-CCP3) levels: -Pre-screening: - first degree relatives of patients with RA; - subjects at health-fairs; and - identification of subjects with elevated anti-CCP3 levels in the absence of inflammatory arthritis in rheumatology clinics.

Details

Rheumatoid arthritis (RA) affects an estimated 1% of the population. RA is a disease where the immune system attacks the joints, leading to joint inflammation and damage that is felt by someone with RA as joint pain, stiffness and swelling.

Recent studies have shown that there are markers in the blood called 'autoantibodies' that precede the onset of joint symptoms of RA. Antibodies are commonly made in the blood to fight infections. Sometimes, these antibodies attack one's own body. These are called autoantibodies.

Certain autoantibodies are specific for certain diseases. The autoantibody known as anti-CCP is specific for RA and can predict the development of RA in the future, especially if the level of anti-CCP is high. The investigators of this study believe that individuals with elevations of anti-CCP greater than 2 times the normal value have approximately a 50% chance of developing RA within 3 years.

Hydroxychloroquine (HCQ) is already used successfully and safely in the treatment of malaria, lupus and RA. The objective of this study is to determine whether treatment with HCQ in individuals with elevations of anti-CCP without joint inflammation may help prevent the future onset of RA. This will involve a 12-month course of HCQ in the prevention of the development of clinically apparent RA at 36 months in individuals at high-risk for future RA due to high titer elevations of anti-CCP3. This study will recruit for individuals without a history or clinical findings of inflammatory arthritis. Eligible subjects will be randomized in a 1:1 ratio to HCQ versus HCQ placebo.

Keywords

Healthy Participants Rheumatoid Arthritis (RA) Prevention RA prevention hydroxychloroquine (HCQ) anti-CCP Hydroxychloroquine

Eligibility

You can join if…

Open to people ages 18 years and up

Subjects who meet all of the following criteria are eligible for enrollment into the study:

  • Able and willing to give written informed consent and comply with requirements of the study;
  • Age ≥18 years-old at the Screening Visit; and
  • Elevation of autoantibody anti-cyclic citrullinated peptide (anti-CCP) defined by result of anti-CCP ≥40 units, at Screening.

You CAN'T join if...

Subjects who meet any of the following criteria are ineligible to participate in the study:

  • Evidence of significant retinal disease that, in the opinion of the examiner, would make identification of potential future retinal toxicity from hydroxychloroquine difficult to evaluate;
  • A medical history of inflammatory arthritis (IA) of any type and/or rheumatic disease and immunologic disease(s) that may be associated with IA. These diseases include but are not limited to:
  • RA;
  • systemic lupus erythematosus (SLE);
  • seronegative spondyloarthropathies;
  • inflammatory bowel disease;
  • Sjögren's syndrome;
  • polymyalgia rheumatic; and
  • vasculitis.

Subjects with crystalline arthropathies do not need to be excluded.

  • Prior or current systemic treatment with disease modifying anti-rheumatic agents,immunomodulatory agents, or glucocorticoids for IA, other rheumatic diseases, or other immunologic diseases;
  • Minocycline or systemic corticosteroid use for non-IA conditions taken 12 months prior to Screening Visit;
  • A history of a chronic condition that, in the opinion of the investigator, is highly likely to require therapy with systemic corticosteroids (oral or intravenous) within the study period, including but not limited to severe asthma and severe crystalline arthropathy;
  • Women who are pregnant, breastfeeding or desire to become pregnant and/or breast feed within the duration of the 12-month treatment phase of the study;
  • Women of childbearing potential who are not using or who do not agree to use adequate birth control measures (for example, total abstinence, oral contraceptives,intrauterine device, barrier method with spermicide, surgical sterilization,Depo-Provera, or hormonal implants) during the treatment phase of the study;
  • A medical history of:
  • congestive heart failure or functional status of New York Heart Association(NYHA) Class III or higher at the Screening Visit;
  • cardiomyopathy or significant cardiac conduction disorders;
  • cirrhosis;
  • psoriasis (due to potential for increased risk for flare of skin disease);
  • porphyria;
  • chronic infections including, but not limited to, human immunodeficiency virus(HIV), hepatitis B (HBV), or hepatitis C (HCV) at Screening Visit;
  • malignancy within the last 5 years, except for treated basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ cervical cancer Grade I;
  • alcohol or substance abuse within 1 year of treatment randomization;
  • An ideal or actual body weight ≤ 24.4 kg (e.g., ≤53 lbs) at Screening Visit;
  • Any of the following laboratory abnormalities at the Screening Visit:
  • Serum Creatinine Clearance < 50ml/min (as calculated by the Cockcroft-Gault formula: Creatinine clearance (CrCl)= (140-age) X (Weight in kg) X (0.85 if female) / (72 X Creatinine));
  • Alanine Aminotransferase (ALT) > 2 times the upper limit of normal (ULN);
  • Total white blood count (WBC) < 3.0 x 109/L;

  • Platelet count ≤ 150 x109/L;

  • Hemoglobin < 11.5g/dL;
  • Absolute Neutrophil Count (ANC) < 2.0 x 109/L;

  • Model for End-Stage Liver Disease (MELD) score ≥10;
  • Hepatitis C antibody positivity;
  • Hepatitis B surface antigen positivity;
  • That, in the opinion of the study physician, is not a good study candidate.

Locations

  • Cedars Sinai Medical Center: Division of Rheumatology accepting new patients
    Los Angeles, California, 90048, United States
  • UCLA Medical Center: Division of Rheumatology accepting new patients
    Los Angeles, California, 90095, United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Links
National Institute of Allergy and Infectious Diseases (NIAID)
Division of Allergy, Immunology, and Transplantation (DAIT)
Autoimmunity Centers of Excellence (ACE)
ID
NCT02603146
Phase
Phase 2
Lead Scientist
Jonathan Graf
Study Type
Interventional
Last Updated
July 1, 2017
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