Clinical trial NCT00000401: Oral Collagen for Rheumatoid Arthritis
Official title: Open Label Multicenter Induction of CII Tolerance in Patients With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: NSAIDs
Oral Tolerance
Drug Interaction
Oral Administration
Interleukin 10
Collagen
Chemotherapy
Human Therapy Evaluation
DMARDs
RA
IL-10
Lead sponsor: University of Tennessee
Sponsor class: OTHER
Collaborators: name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 1999-11-04
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Rheumatoid arthritis (RA) is an autoimmune disease characterized by swelling and inflammation of the joints. In RA, the immune system attacks a person's own cells inside joints, eventually leading to joint damage and disability. This study will determine if oral bovine type II collagen (bovine CII) will lead to decreased joint inflammation in RA patients.

Detailed description: RA is an inflammatory disease that causes pain, swelling, stiffness, and loss of function in the joints. The study will evaluate the effects of using oral bovine CII on RA patients by assessing the levels of inflammation markers such as interferon gamma (IFN-gamma), interleukin-10 (IL-10), and transforming growth factor beta (TGF-beta). This study is a multicenter clinical trial to be conducted at the University of Tennessee, Memphis (the lead center) and the West Tennessee Medical Specialty Clinic (a collaborating site).

Patients enrolled will be allowed to continue a constant dose of disease-modifying anti-rheumatic drugs (DMARDs) and prednisone less than or equal to 7.5 mg/day. Patients will be randomly assigned to one of two groups. The low dose group will receive 30 mcg daily for 10 weeks, then 50 mcg daily for 10 weeks, followed by 70 mcg daily for 10 more weeks; the high dose group will receive 90 mcg daily for 10 weeks, then 100 mcg daily for 10 weeks, followed by 130 mcg daily for 10 more weeks. Blood will be collected at screening and at Weeks 10, 20, and 30. Blood will be analyzed for indicators of inflammation.

Note: this trial is no longer being conducted as an intervention trial. Accrual has been discontinued, although patients previously enrolled are still being followed.

Eligibility criteria: Note: accrual into this trial has been discontinued, but patients previously enrolled are still being followed.

Inclusion Criteria:

* Clinically stable RA and unlikely to require adjustment of doses of DMARDs, NSAIDs, prednisone, or anti-TNFα therapies for the treatment phase of the study
* Meets American College of Rheumatology (ACR) 1988 revised criteria for RA
* Onset of disease at age 16 or older
* Onset of disease at least 3 months prior to enrollment
* PBMC - IFNγ - α1(II)/PBS stimulation index greater than or equal to 1.5 in 6 months prior to baseline visit
* Agree to discontinue herbal remedies described in this protocol
* Agree to use acceptable forms of contraception

Exclusion Criteria:

* Participation in another clinical research study involving the evaluation of another investigational drug within 90 days prior to study entry
* Currently taking greater than 7.5 mg prednisone daily
* Intra-articular corticosteroid injections within 30 days prior to study entry
* Concurrent serious medical condition which, in the opinion of the investigator, makes the patient inappropriate for the study
* Pregnancy
* Beef allergy
* Use of fish oil within 4 weeks of study entry
* Previous use of auranofin or cyclophosphamide (all other DMARDs are allowed)
* Previous autologous or heterologous stem cell transplantation
* Active malignancy or past treatment consisting of antineoplastic drugs or total lymphoid irradiation
* Intolerance to citrus juices or colorless carbonated beverages

Primary outcomes:
measure: Repeated measures analysis of variance with contrasts to determine if the change in the PBMC-IFN gamma-alpha 1(II)/PBS stimulation index is significantly at the 0.05 level and/or greater than or equal to 30%.
timeFrame: Before and after each 10-week treatment
Secondary outcomes:
measure: A Pearson correlation coefficient will be calculated for the change in the PBMC-INF gamma-alpha1(II)/PBS stimulation index and the change in the reactivity to RA CII epitope alpha 1 (II) CB11 for each dose.
timeFrame: Before and after each 10-week treatment
Other outcomes:
Locations:
city: Jackson
country: United States
facility: The Arthritis Clinic of Jackson, PLLC
state: Tennessee
city: Memphis
country: United States
facility: University of Tennessee, Memphis
state: Tennessee
Study officials:
affiliation: University of Tennessee at Memphis Department of Medicine
name: Arnold E. Postlethwaite, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Postlethwaite AE. Can we induce tolerance in rheumatoid arthritis? Curr Rheumatol Rep. 2001 Feb;3(1):64-9. doi: 10.1007/s11926-001-0052-z.
citation: Carbone LD, McKown K, Pugazhenthi M, Barrow KD, Warrington K, Somes G, Postlethwaite AE. Dosage effects of orally administered bovine type I collagen on immune function in patients with systemic sclerosis. Arthritis Rheum. 2004 Aug;50(8):2713-5. doi: 10.1002/art.20361. No abstract available.