Clinical trial NCT00000435: dnaJ Peptide for Relieving Rheumatoid Arthritis
Official title: A Clinical Trial of Shared Epitope Peptides in Rheumatoid Arthritis (RA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: RA
Immune Modulation
Oral Tolerance
Peptide
dnaJ
Lead sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Sponsor class: NIH
First posted: 2000-01-24
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A small protein called dnaJ peptide may help people with rheumatoid arthritis (RA) by preventing their immune system cells from attacking their own tissues. The purpose of this study is to determine if small amounts of dnaJ peptide can "re-educate" immune cells in people with RA so that the cells stop attacking joint tissues.

Detailed description: Immune modulation is a promising new approach for the treatment of RA. Studies have shown that immune cells in the joints of people in the early stages of RA react strongly against dnaJ peptides from bacteria. These immune cells may also cross-react with human dnaJ peptides in the joints to cause inflammation. dnaJ may help RA by "re-educating" the immune system and dampening the abnormal inflammatory immune response in RA.

This study will last 7 months. Participants will be randomly assigned to receive either dnaJ or placebo by mouth. At screening, participants will have medical history, physical, and medication assessment. At screening, at 6 study visits every month after the start of treatment, and at 1 month follow-up, participants will have a joint exam, blood and urine collection, and will fill out a questionnaire about their condition.

Eligibility criteria: Inclusion Criteria:

* Active rheumatoid arthritis as defined by the revised American College of Rheumatology (ACR) 1987 criteria. Evidence of active disease will be based on at least six swollen or nine tender joints.
* Diagnosis of rheumatoid arthritis of less than 5 years
* Reactivity to dnaJ
* Agree to use acceptable methods of contraception
* Able to understand and sign informed consent

Exclusion Criteria:

* Patients taking more 7.5 mg of prednisone or disease modifying agents other than hydrochloroquine or sulfasalazine (i.e., gold, penicillamine, azathioprine, cyclophosphamide, methotrexate, cyclosporine, or anti-TNF agents)
* Serum creatinine greater than 1.5 mg/dl
* SGOT less than SGPT
* Alkaline phosphatase greater than 2 times age/sex adjusted normal values
* Hematocrit of less than 30
* Platelets less than 130,000
* History of lymphoma
* Any active malignancy or cancer requiring treatment in the last 5 years, except for nonmelanoma skin cancers and carcinoma of the cervix in situ
* Medical or psychiatric condition or active serious infection
* Pregnant or breastfeeding

Primary outcomes:
measure: Area under the curve or 'AUC' obtained by adding 0 for no response and 1 for an ACR 20 response for visits on Day 112, 140, and 168
timeFrame: time points 112, 140 and 168 of the 6-month trial
Secondary outcomes:
measure: Day 112 ACR 20 score
timeFrame: Visit day 112 of the 6-month trial
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Health Sciences Center
state: Arizona
city: Orange
country: United States
facility: University of California, Irvine Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: Denver Arthritis Center
state: Colorado
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Sayre
country: United States
facility: Guthrie Clinic
state: Pennsylvania
city: Seattle
country: United States
facility: Virginia Mason Research Center
state: Washington
Study officials:
affiliation: University of California, San Diego
name: Salvatore Albani, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Prakken BJ, Samodal R, Le TD, Giannoni F, Yung GP, Scavulli J, Amox D, Roord S, de Kleer I, Bonnin D, Lanza P, Berry C, Massa M, Billetta R, Albani S. Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4228-33. doi: 10.1073/pnas.0400061101. Epub 2004 Mar 15.
citation: Koffeman EC, Genovese M, Amox D, Keogh E, Santana E, Matteson EL, Kavanaugh A, Molitor JA, Schiff MH, Posever JO, Bathon JM, Kivitz AJ, Samodal R, Belardi F, Dennehey C, van den Broek T, van Wijk F, Zhang X, Zieseniss P, Le T, Prakken BA, Cutter GC, Albani S. Epitope-specific immunotherapy of rheumatoid arthritis: clinical responsiveness occurs with immune deviation and relies on the expression of a cluster of molecules associated with T cell tolerance in a double-blind, placebo-controlled, pilot phase II trial. Arthritis Rheum. 2009 Nov;60(11):3207-16. doi: 10.1002/art.24916.