Glucosamine Unum In Die [Once A Day] Efficacy (GUIDE) Trial: Glucosamine Sulfate in Patients With Knee Osteoarthritis
Condition: Knee Osteoarthritis
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

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.
    

Intervention name(s): Glucosamine sulfate; Acetaminophen
Intervention type(s): Drug; Drug
Intervention MeSH terms: Acetaminophen
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Glucosamine sulfate; Osteoarthritis; Acetaminophen; Paracetamol; Clinical trial