Determining Disease Activity Biomarkers in Individuals With Polyarteritis Nodosa

Longitudinal Protocol of Polyarteritis Nodosa

Polyarteritis nodosa (PAN) is a rare immune system disorder that causes swelling and damage to small- and medium-sized blood vessels in the body. In order to properly treat this disease, it is critical that the level of disease activity can be determined over the course of the disease. The purpose of this study is to determine new biological markers, or biomarkers, that may be used to assess the severity of disease in people with PAN.

Study Overview

• Status: Completed
• Conditions: Polyarteritis Nodosa

Detailed Description

PAN, also known as systemic necrotic vasculitis, was the first recognized form of primary systemic vasculitis. PAN causes the inflammation of small- to medium-sized blood vessels, especially those supplying the nerves, skin, kidneys, gastrointestinal tract, heart, eye, and genitals. Unlike another form of vasculitis called microscopic polyangiitis, PAN does not usually cause glomerulonephritis, a type of kidney disease, or vasculitis in the very smallest blood vessels (arterioles, capillaries, and venules). There are no radiographic or serologic tests that can reliably measure disease activity in PAN. Currently, clinicians must rely on patients' symptoms, signs, laboratory tests, and imaging to guide treatment decisions, but such data are rarely consistently reliable in determining PAN disease activity. This study will use new scientific methods to discover new biomarkers that can be used to monitor disease activity in PAN patients. These biomarkers may be used to help direct clinical care for PAN patients and assist in future drug development.

Study visits will occur monthly for the first year, then every 3 months thereafter for the remainder of the study. Blood and urine collection will occur at every visit. A physical exam and medical and medication history will occur every 3 months; also, participants will be asked to complete several questionnaires to assess disease activity, health status, and tobacco, alcohol, and drug use. Participants may have additional study visits if a disease flare or disease-related complications occur during the study.

• Study Type: Observational
• Enrollment (Actual): 107

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada
      • St. Joseph's Healthcare
    • Toronto, Ontario, Canada, M5T 3L9
      • Mount Sinai Hospital
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02118
      • Boston University School of Medicine
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic College of Medicine
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15260
      • University of Pittsburgh
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Individuals with polyarteritis nodosa. Enrollment will be sequential and participants will have disease in various stages and of different duration.

Description

Inclusion Criteria:

• Parent or guardian willing to provide informed consent, if applicable
• Diagnosis of vasculitis
• Diagnosis of PAN, meeting at least 1 major criterion and 1 minor criterion OR 2 major criteria of the following adapted American College of Rheumatology (ACR) criteria that fall under the diagnosis of PAN and that are not explained by other causes:

MAJOR CRITERIA

1. Arteriographic abnormality
2. Presence of granulocyte or mixed leukocyte infiltrate in an arterial wall on biopsy
3. Mononeuropathy or polyneuropathy

MINOR CRITERIA

1. Weight loss of more than 4 kg (8.8 lbs)
2. Livedo reticularis, cutaneous ulcerations, or skin nodules
3. Testicular pain or tenderness
4. Myalgias
5. Diastolic blood pressure greater than 90 mm Hg
6. Elevated blood urea nitrogen (BUN) or serum creatinine levels
7. Ischemic abdominal pain

Exclusion Criteria:

• Microscopic polyangiitis
• Granulomatosis with polyangiitis(Wegener's)
• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
• Takayasu's arteritis
• Giant cell arteritis
• Cogan's syndrome
• Behcet's disease
• Sarcoidosis
• Kawasaki disease
• Cryoglobulinemic vasculitis
• Systemic lupus erythematosus
• Rheumatoid arthritis
• Mixed connective tissue disease or any overlap autoimmune syndrome
• Presence of antiproteinase 3 or antimyeloperoxidase antineutrophil cytoplasmic antibodies (ANCA)
• Glomeronephritis
• Alveolar hemorrhage
• Hepatitis B, hepatitis C, or HIV infection
• Any other infectious form of medium vessel vasculitis
• Isolated cutaneous PAN

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Discover biomarkers in PAN capable of measuring disease activity and response to treatment.	Study completion

Secondary Outcome Measures

Outcome Measure	Time Frame
Measure the predictive value of biomarkers for clinical outcome in PAN.	Study completion.

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Rare Diseases Clinical Research Network; Office of Rare Diseases (ORD)

Publications and helpful links

General Publications

• Bonsib SM. Polyarteritis nodosa. Semin Diagn Pathol. 2001 Feb;18(1):14-23.
• Said G, Lacroix C. Primary and secondary vasculitic neuropathy. J Neurol. 2005 Jun;252(6):633-41. doi: 10.1007/s00415-005-0833-9. Epub 2005 Apr 5.

Helpful Links

• Vasculitis Clinical Research Consortium
• Rare Diseases Clinical Research Network

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2006
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: April 14, 2006
• First Submitted That Met QC Criteria: April 14, 2006
• First Posted (Estimate): April 18, 2006

Study Record Updates

• Last Update Posted (Actual): July 12, 2022
• Last Update Submitted That Met QC Criteria: July 11, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: PAN; Periarteritis Nodosa
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Vasculitis; Skin Diseases, Vascular; Systemic Vasculitis; Arteritis; Polyarteritis Nodosa
• Other Study ID Numbers: VCRC5504; U54AR057319 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No