Efficacy of 3 Weekly Injections of Hyaluronate in Patients With Ankle Osteoarthritis

Hyaluronans in the Treatment of Ankle Osteoarthritis

The aim of this study was to investigate the efficacy and safety of three weekly intraarticular injections of Hyaluronate (HA) in patients with unilateral ankle Osteoarthritis (OA).

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: sodium hyaluronate

Detailed Description

Viscosupplementation with 3 to 5 weekly hyaluronate injections is a well-established treatment option in knee osteoarthritis. Previous studies reported that five weekly hyaluronate injections were safe and effective for the treatment of ankle osteoarthritis. However, the effect of three weekly injections has rarely been investigated. Besides, no study to date has assessed whether balance function would change after HA injections in patients with ankle OA. The purpose of this study was to evaluate the efficacy and safety of three weekly injections of sodium hyaluronate (Hyalgan) in patients with unilateral ankle osteoarthritis. Pain, physical function and balance will be assessed as parameters for the effectiveness.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung, Taiwan, 813
    • Department of Physical Medicine and Rehabilitation, Veterans General Hospital, Kaohsiung, Taiwan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• were 18 years of age or older, reported unilateral ankle pain for at least 6 months and had either reported no significant benefit from conservative treatment (rest, physical therapy, orthoses or pain medications etc.) or were unable to tolerate side effects of medications
• ankle radiographs taken within 6 months were equivalent to grade 2 or 3 according to the Kellgren-Lawrence grading system (grade 2, definite osteophytes and possible narrowing of joint space; grade 3, moderate multiple osteophytes, definite narrowing of joint space, some sclerosis and possible deformity of bone contour)22
• had a current total AOS score (described below) of > 3 and < 9 (possible range, 0-10)
• were normally active, not bedridden or confined to a wheelchair, and were able to walk 30 meters without the aid of a walker, crutches or cane
• were willing to discontinue all nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesic medication (except for rescue medication) for the duration of the study
• did not receive physical therapy or trial of shoe modifications or orthotics during the study period

Exclusion Criteria:

• pregnant and lactating women
• bilateral ankle OA requiring treatment of both ankles
• chronic ankle instability
• lower leg trauma other than within the ankle
• previous orthopedic surgery on the spine, hip or knee
• presence of active joint infections of foot or ankle
• previous surgery or arthroscopy on the ankle within 12 months
• intraarticular steroid or HA injection in the treated ankle within the past 6 months
• treatment with anticoagulants or immunosuppressives
• history of rheumatoid arthritis, gout, or any other inflammatory arthropathy
• history of avian protein allergy
• presence of other comorbidity (neoplasm, diabetes mellitus, paresis, recent trauma, etc) or poor health status that would interfere with the clinical assessments during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hyaluronate injection; All patients with unilateral ankle OA received 3 weekly intraarticular injections of 2 ml sodium hyaluronate (Hyalgan) into the ankle joints.	Drug: sodium hyaluronate; 3 weekly intraarticular injections of 2 ml sodium hyaluronate (Hyalgan) into the ankle joints.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Ankle Osteoarthritis Scale (AOS) Score at 6 Months	The AOS is a patient-rated, validated outcome measure that includes nine items on a pain subscale and nine items on a disability subscale. Using the AOS, a score of 0 represent no pain or disability and 10 represent worst pain or disability imaginable	baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The American Orthopedic Foot and Ankle Society (AOFAS) Ankle/Hindfoot Score	The American Orthopedic Foot and Ankle Society (AOFAS) ankle/hindfoot score is a 100-point scale that devotes 40 points to pain, 50 points to function and 10 points to alignment. The maximum score of 100 points denotes no pain and normal function and alignment	6 months
Ankle Sagittal Range of Motion	Ankle sagittal ROM is the sum of ankle dorsiflexion and plantar flexion angles.	6 months
Four Clinical Balance Tests	Single-leg stance test (SLS),The Functional Reach Test (FRT),Timed " Up-and-Go" test (TUG) ,Berg Balance Scale (BBS)	6 months
the Level of Global Satisfaction Based on a 7-point Categorical Scale	The rating was based on a 7-point categorical scale weighted from completely satisfied, satisfied, somewhat satisfied, no change, somewhat unsatisfied, unsatisfied to completely unsatisfied.	6 months
Systemic and Local Adverse Events Recording	he occurrence of systemic and local adverse events, defined as any unwanted events whether it was thought to be related to the study drugs or not, were recorded on a diary card	6 months
Rescue Acetaminophen Consumption	The use of all analgesic medication during the study period was recorded on a diary card by the patient.	6 months

Collaborators and Investigators

• Sponsor: Kaohsiung Veterans General Hospital.
• Collaborators: National Science Council, Taiwan
• Investigators: Principal Investigator: Shu-Fen Sun, MD, Veterans General Hospital, Kaohsiung, Taiwan

Publications and helpful links

General Publications

• Sun SF, Chou YJ, Hsu CW, Hwang CW, Hsu PT, Wang JL, Hsu YW, Chou MC. Efficacy of intra-articular hyaluronic acid in patients with osteoarthritis of the ankle: a prospective study. Osteoarthritis Cartilage. 2006 Sep;14(9):867-74. doi: 10.1016/j.joca.2006.03.003. Epub 2006 Apr 24.
• Salk RS, Chang TJ, D'Costa WF, Soomekh DJ, Grogan KA. Sodium hyaluronate in the treatment of osteoarthritis of the ankle: a controlled, randomized, double-blind pilot study. J Bone Joint Surg Am. 2006 Feb;88(2):295-302. doi: 10.2106/JBJS.E.00193.
• Cohen MM, Altman RD, Hollstrom R, Hollstrom C, Sun C, Gipson B. Safety and efficacy of intra-articular sodium hyaluronate (Hyalgan) in a randomized, double-blind study for osteoarthritis of the ankle. Foot Ankle Int. 2008 Jul;29(7):657-63. doi: 10.3113/FAI.2008.0657.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: March 16, 2009
• First Submitted That Met QC Criteria: April 24, 2009
• First Posted (Estimate): June 11, 2009

Study Record Updates

• Last Update Posted (Estimate): June 17, 2009
• Last Update Submitted That Met QC Criteria: June 11, 2009
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: Balance; Osteoarthritis; Hyaluronic acid; Ankle joint
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: NSC96-2314-B-075B-006