Glucosamine Unum In Die [Once A Day] Efficacy (GUIDE) Trial: Glucosamine Sulfate in Patients With Knee Osteoarthritis

September 18, 2006 updated by: Rottapharm

Efficacy and Safety of Glucosamine Sulfate Versus a Pure Analgesic (Acetaminophen/Paracetamol) and Placebo in Patients Suffering From Osteoarthritis of the Knee

The primary objective of this study is to evaluate the efficacy and safety of glucosamine sulfate versus placebo on the symptoms of knee osteoarthritis after 6 months of treatment, using acetaminophen as a reference symptomatic medication.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Osteoarthritis is a common degenerative joint disease, affecting a large proportion of the general population. Its severity is progressive and often requires long-term treatment courses.

Medications for osteoarthritis may affect symptoms (pain and function limitation) and/or modify joint structure.

Pharmacological agents usually employed to treat symptoms generally include unspecific drugs such as pure analgesics and non-steroidal antiinflammatory drugs (NSAIDs), as well as compounds that are possibly disease specific, since they probably interact with some of the osteoarthritis pathogenetic factors: glucosamine sulfate is one of these agents.

Glucosamine sulfate has recently attracted the attention of the scientific community and of patients, because two long-term (3 years) clinical trials in comparison with placebo, showed that this is the first agent able to retard the progression of anatomic joint structure changes in knee osteoarthritis, besides controlling the progression of symptoms.

Earlier studies had shown that glucosamine sulfate is effective in relieving the symptoms of osteoarthritis also over shorter treatment courses (few weeks or months), in comparison with placebo. In addition, glucosamine sulfate efficacy in short studies was at least comparable to that of unspecific symptomatic medications such as conventional NSAIDs, whilst being better tolerated. However, all practice guidelines for the treatment of osteoarthritis suggest acetaminophen (paracetamol) as the oral analgesic to try first and, if successful, the preferred long-term symptomatic medication.

This trial was therefore designed to confirm the efficacy of glucosamine sulfate in comparison with placebo and to assess its relative value compared with acetaminophen. In fact, superiority of a well tolerated drug such as glucosamine sulfate and with the long-term treatment potential shown in other trials, may represent a major therapeutic advantage.

The treatment has a duration of 6 months, that is believed to be the minimum length to assess the effects of a symptomatic medication in osteoarthritis.

The study is performed according to a multicenter, randomised, placebo- and reference-controlled, double-blind (double-dummy), parallel group, prospective design.

The sample size has been calculated on the basis of the expected efficacy of the test drug on the primary outcome (Lequesne index).

Following a screening visit and a short baseline period to check adherence to the inclusion/exclusion criteria, a total of at least 300 patients with knee osteoarthritis are randomised to receive either oral glucosamine sulfate soluble powder 1500 mg once-a-day, or acetaminophen tablets 1000 mg three times a day (total 3g/day, as recommended in Europe), or placebo, for 6 months. The rescue medication for flare episodes consists of the standardized use (according to specific instructions given to the patients) of ibuprofen 400 mg tablets, whose consumption is recorded in a patient daily diary.

The primary efficacy outcome measure is represented by the change in the Lequesne algo-functional index (assessed at clinic visits) after 6 months in the intention-to treat population, analysed by the General Linear Model (GLM) procedure for ANOVA, with Dunnet's pairwise comparisons versus placebo. Efficacy in patients completing treatment according to the protocol (per-protocol completers) will be also assessed. Secondary efficacy outcome measures include the changes in the WOMAC index and the calculation of the proportion of patients that can be defined responders to treatment according to the Osteoarthritis Research Society International (OARSI) criteria (2000). The use of the rescue medication is also assessed.

Safety is assessed by reporting of adverse events and by routine laboratory tests.

The glucosamine sulfate substance used in this trial (crystalline glucosamine sulfate) is a prescription drug in Europe and elsewhere, mostly used in its 1500 mg powder for oral solution formulation to be administered once daily. This is the substance/formulation that was effective and safe in the vast majority of glucosamine clinical trials, including the long-term, 3-year studies.

Differently than in Europe and other countries, glucosamine formulations are marketed in the United States as dietary supplements. They include glucosamine sulfate substances different than the original prescription preparation, other glucosamine salts (mainly glucosamine hydrochloride), and are administered according to different dosage schemes (mainly as oral solid formulations that provide a total 1500 mg dose, but divided in three daily intakes, t.i.d.). In clinical trials conducted so far, these formulations failed to show the same efficacy of the original glucosamine sulfate prescription preparation.

The present study uses therefore the original prescription crystalline glucosamine sulfate given once-a-day (unum-in-die, u.i.d.) and it is therefore named the Glucosamine Unum In Die Efficacy (GUIDE) Trial.

Study Type

Interventional

Enrollment

300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Portugal
      • Coimbra, Portugal
        • Hospital Universitário de Coimbra
      • Lisboa, Portugal
        • Hospital Egaz Moniz
      • Ponte de Lima, Portugal
        • Hospital Conde do Bertiandos
  • Spain
      • A Coruña, Spain
        • Complejo Hospitalario Juan Canalejo
      • Barcelona, Spain
        • Hospital Del Mar
      • Barcelona, Spain
        • Hospital Clinic
      • Ciudad Real, Spain
        • Completo Hospitalario de Ciudad Real
      • Madrid, Spain
        • Fundacion Jimenez Diaz
      • Madrid, Spain
        • Hospital Universitario La Paz
      • Madrid, Spain
        • Hospital de La Pricesa
      • San Sebastian, Spain
        • Hospital Donostia
      • Sevilla, Spain
        • Hospital Nuestra Senora de Valme
      • Valencia, Spain
        • Hospital Dr. Peset

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of knee osteoarthritis according to the clinical and radiological criteria of the American College of Rheumatology (ACR), with minimum symptom severity/characteristics

Exclusion Criteria:

  • Standard exclusions apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Lequesne Index

Secondary Outcome Measures

Outcome Measure
WOMAC Index
OARSI Responder Criteria

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rottapharm

Investigators

  • Study Director: Gabriel Herrero-Beaumont, MD, Fundacíón Jiménez Díaz - Madrid - Spain

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2000

Study Completion

December 1, 2002

Study Registration Dates

First Submitted

May 9, 2005

First Submitted That Met QC Criteria

May 9, 2005

First Posted (Estimate)

May 10, 2005

Study Record Updates

Last Update Posted (Estimate)

September 19, 2006

Last Update Submitted That Met QC Criteria

September 18, 2006

Last Verified

September 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JN151198

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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