Ostearthritis Biomarkers and Rehabilitation

Summary

Osteoarthritis (OA) is the most common type of degenerative joint disease. Furthermore, despite its incidence being amongst the highest in chronic diseases, effective biomarkers, diagnostic aids and imaging technology are not available to assist in the management of OA. Mounting evidence suggests that non-pharmacological treatment such as exercise/physical therapy may lower the risk for onset or progression of OA by mitigating inflammation. However, the mechanical unloading and overloading, as seen in disuse and overuse, lead to upregulation of several proinflammatory molecules and enhance tissue degradation, whereas, dynamic moderate mechanical loading exerts anti-inflammatory and anti-catabolic effects on articular cartilage by suppressing mediators of inflammation. However, the lack of robust biomarkers to measure the effectiveness of physical therapies, represent a critical gap in biotechnology, obliterating the progress in the optimal application of these therapies. Our central hypothesis is that the circulating levels of specific molecules could serve as robust biomarkers for quantitative measures of OA burden, prognosis, progression or treatment efficacy. The objective of this project is to identify and evaluate mediators that serve as biomarkers of OA progression and treatment. Recently, high mobility group box chromosomal protein 1 (HMGB-1) has been suggested to be markedly upregulated in OA. However, presently there are no inhibitors of HMGB1 that could be used therapeutically. Previous results showed that that gentle exercise is the only tool that can mitigate HMGB1 production by local and systemic macrophages, and thus inflammation. Serum concentration of HMGB1 will be evaluate as a biomarker in OA patients and relate it to the functional capacity of knee joints in OA patients after rehabilitation protocol (RP). The RP will consist of three rehabilitation session/week during eight weeks. The efficacy of a RP will be evaluated by functional scale Western Ontario \& McMaster Universities Osteoarthritis (WOMAC), Scale for the measurement of health related quality of life using EuroQol five dimensions questionnaire (EuroQOL), Visual Analog Scale (VAS), and physical function tests. Besides all clinical assessment, serum levels of classical pro-inflammatory cytokines, hyaluronan and HMGB1 will be evaluated. A correlation of physical improvement after RP and serum biomarkers will be performed.

Conditions

• Osteoarthritis

Interventions

OTHER

Rehabilitation

Protocol will consist of three exercise/week for eight weeks. Each session will begin with the evaluation of pain by the volunteer. Starting with a warm up exercise in a cycle ergometer (CEE), for 5 minutes at free cadence, then the intensity will be set at 90% of the intensity obtained during the incremental test and maintained for 10 min. Afterward, four sets of three different resistance exercises (RE) will be performed at 70% of the load correspondent to 1RM test with one minute interval between sets and exercises. During CEE Borg scale will be taken every two minutes and during RE the OMNI scale taken at the end of every set to monitor the intensity. At the end of the session, cool down global stretching exercises for inferior members will be performed and the VAS evaluated.

Sponsors & Collaborators

• Ohio State University

  collaborator OTHER

• Federal University of São Paulo

  collaborator OTHER

• Hospital Israelita Albert Einstein

  lead OTHER

Principal Investigators

• Mario Ferretti, PhD · Hospital Israelita Albert Einstein

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

45 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-07-02

Primary Completion

2019-08-30

Completion

2019-12-30

Countries

• Brazil

Study Locations