Efficacy Study of Condrosulf in the Treatment of Symptomatic OA of the Hand

Clinical Evaluation of Condrosulf 800 mg in the Treatment of Symptomatic OA of the Hand: a 6-month, Double-blind, Placebo Controlled Study

The goal of the present study is to investigate the effectiveness of Condrosulf® 800 mg tablets vs. placebo once a day for 6 months in the symptomatic treatment of finger joint osteoarthritis.

Primary endpoints of the study are the evaluation of global spontaneous pain (Huskisson's Visual Analogue Scale: VAS) and the score of Dreiser's algo-functional index (FIHOA) during the treatment with the tested product, Condrosulf®, versus placebo.

Study Overview

• Status: Completed
• Conditions: Osteoarthrosis
• Intervention / Treatment: Drug: Chondroitin 4&6 sulfate (Condrosulf); Other: Placebo

Detailed Description

The goal of the present study is to investigate the effectiveness of Condrosulf® 800 mg tablets vs. placebo once a day for 6 months in the symptomatic treatment of finger joint osteoarthritis in 160 randomised patients.

Primary endpoints:

Primary endpoints of the study are the evaluation of global spontaneous pain (Huskisson's Visual Analogue Scale: VAS) and the score of Dreiser's algo-functional index (FIHOA) during the treatment with the tested product, Condrosulf®, versus placebo.

Secondary endpoints are:

Efficacy evaluation: Global impression of efficacy expressed by the patient and the physician (VAS), Grip strength (measured manometrically); Morning stiffness duration; Consumption of Paracetamol; Tolerability (4-point verbal scale); Adverse Events occurring during the treatment period; Other parameters:Treatment compliance; Biological markers of arthritis

• Study Type: Interventional
• Enrollment (Actual): 163
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients of either sex
• Aged 40 and over
• Outpatients
• Patients fulfilling the American Congress of Rheumatology (ACR) criteria for the reporting of hand OA
• Patients showing X-ray features of hand OA on at least two joints (2 IP and/or 1 IP and 1 TMC) of the dominant hand on standard plain radiographs (< 6 month).
• Suffering from regular spontaneous pain on the dominant hand (VAS > or = 40 mm at inclusion time).
• Showing a FIHOA score > or = 6.
• Having had at least two painful flares in a finger joint during the previous 12 month.
• Patients who have signed the written informed consent for their participation in the study
• Patients able to understand and follow the protocol.
• Patients with a satisfying health and nutritional status.
• Female subjects of childbearing potential using, within three months prior to the inclusion in the study, a reliable form of contraception during the course of the study (oral contraceptive pill, intrauterine device or condoms) or female of non childbearing potential (hysterectomy, bilateral ovariectomy or tubal section/ligation).
• Female subjects of childbearing potential with a negative urinary pregnancy test before the inclusion in the study.

Exclusion Criteria:

• Inflammatory joint disease of other origin
• Septic arthritis
• Chronic inflammatory joint disease
• Previous articular fracture of the concerned articulations
• Use of analgesic therapy for other indications
• Receiving oral corticosteroids
• Mono-articular posttraumatic OA of the finger
• Planning surgery of the hands in the following 6 months

• Patients suffering or having suffered from secondary osteoarthritis after one of the following diseases:

  • Infectious arthritis - Acromegaly
  • Ochronosis - Hemachromatosis
  • Gout - Wilson's disease
  • Chondrocalcinosis - Paget's disease
  • Osteochondrosis - Mutation of collagen
  • Genetic problems (for ex. hypermobility) - Previous joint fracture
  • Arthropathies of different aetiologies - Algodystrophy (M. Sudeck)
• Congenital abnormalities
• Recurrent pseudogout
• Major dysplasias
• Intra-articular injection in a hand joint from less than 3 months
• Basic treatment of arthritis with symptom-modifying agents (chondroitin sulfate, glucosamine sulfate, diacerhein, hyaluronic acid) in the last 3 months
• Articular lavage in the last 3 months
• Treatment with corticoids, by any administration route during the last month
• Patient suffering from frequent asthma crises
• Physiotherapy, re-education, alternative medicine (mesotherapy, acupuncture) on the hands foreseeable in the next year
• Serious organic diseases: heart failure, renal or hepatic insufficiency, blood dyscrasia, serious infection
• Participation in other clinical trials in the two months preceding the study
• Known or ascertained hypersensitivity to the active ingredient of the tested drug.
• Patients refusing to sign the written informed consent form
• Patients who do not co-operate, not respecting the protocol requirements
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Other: Placebo; 800 mg placebo/day for 6 months
Active Comparator: Chondroitin 4&6 sulfate (Condrosulf)	Drug: Chondroitin 4&6 sulfate (Condrosulf); 800 mg/day for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Global Spontaneous Pain Intensity of Target Hand	Intensity of global spontaneous pain is evaluated by the patient himself on a Huskisson's visual analogue scale (VAS) of 100 mm. 0=no pain 100=max pain Change calculated as difference between Month 6 value and baseline value target hand is defined as the patient's most symptomatic hand or, when both hands were equally painful, the patient's dominant hand.	6 months
Change in Functional Index for Hand Osteoarthritis Dreiser's Score (FIHOA) in the Target Hand	Functional Index for Hand Osteoarthritis (Dreiser's Index). Range 0-30 Patients reported the severity of their symptoms by answering a set of 10 questions. Severity was rated on a numerical scale (0 = possible without difficulty, 1 = possible with slight difficulty, 2 =possible with great difficulty, and 3 = impossible), being 30 points the worst possible pain score. Change calculated as difference between the month 6 value and baseline value Target hand defined as the patient's most symptomatic hand or, when both hands were equally painful, the patient's dominant hand	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator Global Evaluation on Efficacy	Global impression of the efficacy judged by the Investigators at month 6 by means of a visual analogue scale from 0 (no efficacy) to 100 mm (very good efficacy)	6 months
Change in Grip Strength	Grip strength determined on both hands using a Jamar dynamometer.Patients were required to grip the dynamometer handle and squeeze as hard as possible according to their individual pain limits. The right hand grip was measured first, then the left; this procedure was performed 3 times. The mean value of these 3 measurements was recorded. Change calculated as difference between the month 6 value and baseline value	6 months
Change in Morning Stiffness Duration	Change in morning stiffness duration calculated as the difference between the month 6 value and the baseline value	6 months
Consumption of Paracetamol	Total consumption (between ^baseline and month 6) of paracetamol (500 mg tablets) reported by the patients on a daily diary	6 months

Collaborators and Investigators

• Sponsor: IBSA Institut Biochimique SA
• Investigators: Principal Investigator: Cem Gabay, Prof. Dr., HUG Hôpitaux Universitaires de Gèneve

Publications and helpful links

General Publications

• Michel BA, Stucki G, Frey D, De Vathaire F, Vignon E, Bruehlmann P, Uebelhart D. Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: a randomized, controlled trial. Arthritis Rheum. 2005 Mar;52(3):779-86. doi: 10.1002/art.20867.
• Morreale P, Manopulo R, Galati M, Boccanera L, Saponati G, Bocchi L. Comparison of the antiinflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis. J Rheumatol. 1996 Aug;23(8):1385-91.
• Uebelhart D, Malaise M, Marcolongo R, de Vathaire F, Piperno M, Mailleux E, Fioravanti A, Matoso L, Vignon E. Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo. Osteoarthritis Cartilage. 2004 Apr;12(4):269-76. doi: 10.1016/j.joca.2004.01.004. Erratum In: Osteoarthritis Cartilage. 2007 Aug;15(8):979. DeVathaire, Florent [corrected to de Vathaire, Florent].
• Altman R, Alarcon G, Appelrouth D, Bloch D, Borenstein D, Brandt K, Brown C, Cooke TD, Daniel W, Gray R, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand. Arthritis Rheum. 1990 Nov;33(11):1601-10. doi: 10.1002/art.1780331101.
• Lequesne M. [Symptomatic slow-action anti-arthritic agents: a new therapeutic concept?]. Rev Rhum Ed Fr. 1994 Feb;61(2):75-9. No abstract available. French.
• Cicuttini FM, Spector TD. Osteoarthritis in the aged. Epidemiological issues and optimal management. Drugs Aging. 1995 May;6(5):409-20. doi: 10.2165/00002512-199506050-00007.
• Howell DS, Altman RD. Cartilage repair and conservation in osteoarthritis. A brief review of some experimental approaches to chondroprotection. Rheum Dis Clin North Am. 1993 Aug;19(3):713-24.
• Volpi N. Oral bioavailability of chondroitin sulfate (Condrosulf) and its constituents in healthy male volunteers. Osteoarthritis Cartilage. 2002 Oct;10(10):768-77. doi: 10.1053/joca.2002.0824.
• Conte A, de Bernardi M, Palmieri L, Lualdi P, Mautone G, Ronca G. Metabolic fate of exogenous chondroitin sulfate in man. Arzneimittelforschung. 1991 Jul;41(7):768-72.
• Ronca F, Palmieri L, Panicucci P, Ronca G. Anti-inflammatory activity of chondroitin sulfate. Osteoarthritis Cartilage. 1998 May;6 Suppl A:14-21. doi: 10.1016/s1063-4584(98)80006-x.
• Uebelhart D, Thonar EJ, Zhang J, Williams JM. Protective effect of exogenous chondroitin 4,6-sulfate in the acute degradation of articular cartilage in the rabbit. Osteoarthritis Cartilage. 1998 May;6 Suppl A:6-13. doi: 10.1016/s1063-4584(98)80005-8.
• Bourgeois P, Chales G, Dehais J, Delcambre B, Kuntz JL, Rozenberg S. Efficacy and tolerability of chondroitin sulfate 1200 mg/day vs chondroitin sulfate 3 x 400 mg/day vs placebo. Osteoarthritis Cartilage. 1998 May;6 Suppl A:25-30. doi: 10.1016/s1063-4584(98)80008-3.
• Mazieres B, Loyau G, Menkes CJ, Valat JP, Dreiser RL, Charlot J, Masounabe-Puyanne A. [Chondroitin sulfate in the treatment of gonarthrosis and coxarthrosis. 5-months result of a multicenter double-blind controlled prospective study using placebo]. Rev Rhum Mal Osteoartic. 1992 Jul-Sep;59(7-8):466-72. French.
• Bucsi L, Poor G. Efficacy and tolerability of oral chondroitin sulfate as a symptomatic slow-acting drug for osteoarthritis (SYSADOA) in the treatment of knee osteoarthritis. Osteoarthritis Cartilage. 1998 May;6 Suppl A:31-6. doi: 10.1016/s1063-4584(98)80009-5.
• Uebelhart D, Thonar EJ, Delmas PD, Chantraine A, Vignon E. Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study. Osteoarthritis Cartilage. 1998 May;6 Suppl A:39-46. doi: 10.1016/s1063-4584(98)80011-3.
• Verbruggen G, Goemaere S, Veys EM. Chondroitin sulfate: S/DMOAD (structure/disease modifying anti-osteoarthritis drug) in the treatment of finger joint OA. Osteoarthritis Cartilage. 1998 May;6 Suppl A:37-8. doi: 10.1016/s1063-4584(98)80010-1.
• Verbruggen G, Goemaere S, Veys EM. Systems to assess the progression of finger joint osteoarthritis and the effects of disease modifying osteoarthritis drugs. Clin Rheumatol. 2002 Jun;21(3):231-43. doi: 10.1007/s10067-002-8290-7.
• Dreiser RL, Maheu E, Guillou GB, Caspard H, Grouin JM. Validation of an algofunctional index for osteoarthritis of the hand. Rev Rhum Engl Ed. 1995 Jun;62(6 Suppl 1):43S-53S.
• Gabay C, Medinger-Sadowski C, Gascon D, Kolo F, Finckh A. Symptomatic effects of chondroitin 4 and chondroitin 6 sulfate on hand osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial at a single center. Arthritis Rheum. 2011 Nov;63(11):3383-91. doi: 10.1002/art.30574.

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: February 13, 2006
• First Submitted That Met QC Criteria: February 13, 2006
• First Posted (Estimate): February 14, 2006

Study Record Updates

• Last Update Posted (Actual): March 4, 2021
• Last Update Submitted That Met QC Criteria: February 11, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: symptomatic OA of the hand
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: 03CH/Ct06