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
Overview
- Phase
- Phase 2
- Intervention
- Devil Claw
- Conditions
- Osteoarthritis, Knee
- Sponsor
- University of Southampton
- Enrollment
- 67
- Locations
- 1
- Primary Endpoint
- Western Ontario and Mc Master University OA Index (WOMAC)
- Status
- Terminated
- Last Updated
- 14 years ago
Overview
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:
- To compare the efficacy of Devil's Claw with placebo in the treatment of osteoarthritis of the knee and/or hip
- To determine the optimum dose of Devil's Claw and
- 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
Investigators
Dr Sarah Brien
Senior Research Fellow
University of Southampton
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
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
Arms & Interventions
240mg Devil claw
Sub clinical dose if the 3 doses employed
Intervention: Devil Claw
960mg Devil Claw
Active dose
Intervention: Devil Claw
1920 mg Devil claw
Active dose
Intervention: Devil Claw
Placebo
Comparator for all active intervention arms
Intervention: Placebo
Outcomes
Primary Outcomes
Western Ontario and Mc Master University OA Index (WOMAC)
Time Frame: Baseline, week 8 and week 16
WOMAC is a disease specific outcome measure for osteoarthritis. It has three subscales assessing pain (5 questions), stiffness (2 questions) and function (15 questions). together the subscales give an overall total score ranging from 0 (worst) to 100 (best; an increase in total score indicates an improvement in health. THe outcome was measured at baseline, week 8 and week 16. In this study the primary outcome was the reduction in WOMAC total score from baseline to the end of treatment at week 16.
Secondary Outcomes
- Pain Subscale on Western Ontario and Mc Master University OA Index(Baseline, week 8 and week 16)
- Disability Subscale on The Western Ontario and Mc Master University OA Index(baseline, 8 and 16 weeks)
- Stiffness Subscale on the The Western Ontario and Mc Master University OA Index(Baseline, week 8 and week 16)
- Short Form-36 (SF-36)(Baseline, week 8 and week 16)
- Patient Global Assessment(Baseline, week 8 and week 16)
- Complementary and Alternative Medicine Beliefs Inventory(four monthly)
- Adverse Event Reporting(Baseline and weeks 2,4,6,8,12 and 16)