Oral Collagen for Rheumatoid Arthritis

Sponsor

University of Tennessee (Other)

Overall Status

Completed

CT.gov ID

NCT00000401

Collaborator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (NIH)

110

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Oral bovine type II collagen	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

110 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Open Label Multicenter Induction of CII Tolerance in Patients With Rheumatoid Arthritis

Study Start Date :

Jul 1, 1999

Actual Primary Completion Date :

Aug 1, 2005

Actual Study Completion Date :

Aug 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 The low dose group will receive CII 30 mcg daily for 10 weeks, then 50 mcg daily for 10 weeks, followed by 70 mcg daily for 10 more weeks.	Drug: Oral bovine type II collagen Drug can be interrupted or stopped for suspected adverse events. Other Names: CII
Experimental: 2 The high dose group will receive CII 90 mcg daily for 10 weeks, then 100 mcg daily for 10 weeks, followed by 130 mcg daily for 10 more weeks.	Drug: Oral bovine type II collagen Drug can be interrupted or stopped for suspected adverse events. Other Names: CII

Arm

Intervention/Treatment

Experimental: 1

The low dose group will receive CII 30 mcg daily for 10 weeks, then 50 mcg daily for 10 weeks, followed by 70 mcg daily for 10 more weeks.

Drug: Oral bovine type II collagen

Drug can be interrupted or stopped for suspected adverse events.

Other Names:

CII

Experimental: 2

The high dose group will receive CII 90 mcg daily for 10 weeks, then 100 mcg daily for 10 weeks, followed by 130 mcg daily for 10 more weeks.

Drug: Oral bovine type II collagen

Drug can be interrupted or stopped for suspected adverse events.

Other Names:

CII

Outcome Measures

Primary Outcome Measures

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%. [Before and after each 10-week treatment]

Secondary Outcome Measures

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. [Before and after each 10-week treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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