Clinical trial NCT00295490: Trial Evaluating Devil's Claw for the Treatment of Hip and Knee Osteoarthritis
Official title: A Randomized, Double-blind, Placebo-controlled, Dose-ranging Two- Centre Study to Evaluate the Efficacy and Safety of Devil's Claw in the Treatment of Knee and Hip Osteoarthritis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Osteoarthritis, Knee
Osteoarthritis, Hip
Keywords: double blind randomised controlled trial
phase II
Devil's Claw
osteoarthritis of the knee
osteoarthritis of the hip
Lead sponsor: University of Southampton
Sponsor class: OTHER
Collaborators: name: Pascoe Pharmazeutische Praeparate GmbH
First posted: 2006-02-23
Enrollment: 67
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Osteoarthritis of both the knee and hip joints are common conditions; knee osteoarthritis affects 6% of adults over 30 years of age and osteoarthritis of the hip affects between 3% and 6% of the Caucasian population. Both forms of osteoarthritis are associated with disability. Conventional treatment (analgesics and the use non-steroidal anti-inflammatory, NSAIDS) is prophylactic, aimed at decreasing pain and improving function. However long term use of NSAIDS is associated with a high incidence of adverse events (gastrointestinal tract symptoms). A safer alternative treatment would therefore be beneficial.

Both anecdotal evidence and recent studies have implicated the potential of the herbal remedy Devil's Claw (Harpagophytum procumbens) for the treatment of painful, chronic arthritic type conditions (Ernst and Chrubasik, 2000). Devil's Claw is an extract obtained from the root of the Harpagophytum procumbens plant, a member of the sesame family found in the Kalahari region in South Africa. It has been shown that this herbal remedy has anti-inflammatory and analgesic effects (Baghdikian et al, 1997). Currently Devil's Claw is marketed for use as a supportive treatment of degenerative arthrosis, is not a Medicines Control Agency licensed product and is freely available to the general public in health food stores and pharmacies.

The objectives of this study are to assess the efficacy, optimum dosage and safety of the herbal remedy Devil's Claw (Harpagophytum) in the treatment of osteoarthritis of the knee and/or hip. The primary objective of this study is to investigate the following three principal questions:

1. To compare the efficacy of Devil's Claw with placebo in the treatment of osteoarthritis of the knee and/or hip
2. To determine the optimum dose of Devil's Claw and
3. To evaluate the safety and tolerability of three doses of Devil's Claw in the treatment of osteoarthritis of the knee/hip and to compare them to placebo There are also a number of secondary research objectives that will also be addressed (see later).

These objectives are based on the following hypotheses :

Hypotheses

* Devil's Claw has anti-inflammatory properties (as assessed by the reduction in pain, stiffness and disability aspects on the WOMAC) in chronic osteoarthritis of the knee and/or hip after 16 weeks of treatment, as compared to placebo.
* A dose response effect exists in the treatment of osteoarthritis of the knee/hip by Devil's Claw.

Detailed description: STUDY DESIGN: Randomized, placebo-controlled, dose-ranging two-centre study PREPARATIONS FOR INVESTIGATION: Devil's Claw (Allya®)/placebo as tablets

STATISTICAL METHODS:

Analysis on an intention to treat basis.

The following tests will be performed and all statistical significance will be set at p \< 0.05:

Primary efficacy analysis: The primary outcome will be the reduction in WOMAC total score from baseline to week 16. The week 16 means for the four treatment groups will be compared using an analysis of covariance taking account of baseline assessments and any demographic differences, age, gender, etc, which are found to be significant. Multiple comparison tests will be used to examine specific differences of initially specified interest, such as the two highest doses of Devil's Claw versus placebo.

Secondary Efficacy Analysis: Similar analyses of covariance will be used to examine treatment group differences at week 16 compared with baseline for WOMAC subscales (pain, stiffness and physical function), and Quality of Life assessments (SF-36). Changes in the subject's well-being and overall global assessment will be compared using appropriate non-parametric tests, e.g. Mann-Whitney test or MacNemar's test. Changes in attitudes and health beliefs to CAM will be assessed using Chi-Squared tests.

Safety Evaluation: Group differences between adverse event reporting will be assessed by descriptive methods.

NUMBER OF PATIENTS:

264 (50 patients in each group, with an expected total of 64 drop-outs) NUMBER OF SITES: 2

TIME SCHEDULE:

Study Start: April 2004 Study End: March 2007 Observation period/patient: 20 weeks

Eligibility criteria: Inclusion Criteria:

* Patients with either a pragmatic diagnosis of osteoarthritis of the knee, with no other known rheumatological condition and who report the following clinical features (based on the ACR classification for knee OA1):

  * knee pain on most days of the previous month
  * morning stiffness of less than 30 minutes duration
  * "stiffness" in resting the joint and and are aged over 40 years
* osteoarthritis of the hip, with no other known rheumatological condition and who report the following clinical features (based on the ACR classification for hip OA2):

  * hip pain on most days of the previous month and at least two of the following 3 features:
  * ESR \< 20mm/hour
  * Radiographic femoral or acetabular osteophytes
  * Radiographic joint space narrowing (superior, axial and/or medial)
  * And are aged over 45 years of age
* The diagnosis of osteoarthritis will be confirmed by X-ray. Only patients who have grade 2 to 4 of the Kellgren and Lawrence scale will be recruited. (The Kellgren and Lawrence scale ranges from grade 0 to grade 4 where grades 0 and 1 represent doubtful osteoarthritic changes and therefore a doubtful diagnosis.)
* Patients who have been on stable medication (conventional or complementary, including nutritional medicine) for the past three months, but are still getting symptoms (incomplete responders)
* Only those patients who record baseline pain scores on the WOMAC scale of at least 20 mm on the VAS for a minimum of 6 out of 7 days monitored during the period from Clinic Visit 1 (screening) and Clinic Visit 2 (baseline)
* Ability to comply with the requirements of the study and to give informed consent
* For women of child-bearing potential: negative pregnancy test

Exclusion Criteria:

* Participation in an investigational trial within 30 days prior to enrollment
* Previous treatment with Devil' s Claw within 90 days prior to enrollment
* Patients awaiting a replacement knee or hip joint
* Patients with other conditions that cause pain
* Patients with congenital dislocation of the hip
* Patients who have had operations on their hip due to previous trauma
* Patients with severe co-morbidities - including severe cardiac or pulmonary disease and cancer
* Dementia, psychoses, or other significant impairment of mental status that would prohibit sufficient comprehension, provision of informed consent and to allow undertaking of the necessary self-care or toxicity reporting
* Patients taking corticosteroid medication
* Known allergies against any of the ingredients of the treatments
* Patients who would be unable to complete the self assessment forms, or to attend for X-ray and clinical examination
* Patients with other known rheumatic disease such as rheumatoid arthritis
* Patients with the diagnosis gout
* Patients who report a red or hot swollen joint (which is unlikely to be due to OA), and would require further rheumatological assessment
* Patients with conditions known to be contraindicated to the study medication i.e. patients with gastric or duodenal ulcers; gallstones; patients taking drugs for arrhythmias; patients with heart failure
* Patients who are pregnant, trying to become pregnant or breastfeeding

Primary outcomes:
measure: Western Ontario and Mc Master University OA Index (WOMAC)
timeFrame: Baseline, week 8 and week 16
Secondary outcomes:
measure: Pain Subscale on Western Ontario and Mc Master University OA Index
timeFrame: Baseline, week 8 and week 16
measure: Disability Subscale on The Western Ontario and Mc Master University OA Index
timeFrame: baseline, 8 and 16 weeks
measure: Stiffness Subscale on the The Western Ontario and Mc Master University OA Index
timeFrame: Baseline, week 8 and week 16
measure: Short Form-36 (SF-36)
timeFrame: Baseline, week 8 and week 16
measure: Patient Global Assessment
timeFrame: Baseline, week 8 and week 16
measure: Complementary and Alternative Medicine Beliefs Inventory
timeFrame: four monthly
measure: Adverse Event Reporting
timeFrame: Baseline and weeks 2,4,6,8,12 and 16
Other outcomes:
Locations:
city: Southampton
country: United Kingdom
facility: Wellcome Trust Clinical Research Facility, Southampton General Hospital
state: Hants
Study officials:
affiliation: University of Southampton
name: George Lewith, MA MD FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Southampton
name: Sarah Brien, Bsc Msc PhD
role: PRINCIPAL_INVESTIGATOR
References: