Dose Escalation Study Of Chinese Herbs In Osteoarthritis Of The Knee

Study Overview
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Brief Summary
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The purpose of this study is to determine if the traditional Chinese herbal compound (Huo-Luo-Xiao-Ling Dan, or HLXL) is effective in treating OA of the knee in addition to participants current OA of the knee treatment(s) and also to determine the best dosage of HLXL that is safe and well tolerated.

Detailed Description
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The specific aims of this project are: To determine whether HLXL improves pain and/or function in patients with OA of the knee who continue to have symptoms despite receiving standard analgesic and/or anti-inflammatory treatment, To identify an optimal dosage of HLXL, among two dosages, as determined by pain relief and/or functional improvement, in a dose-escalation, placebo-controlled double-blind randomized phase II clinical trial, in conjunction with indicia of safety and tolerability in patients with OA of the knee who are receiving standard analgesic and/or anti-inflammatory treatment, To explore mechanisms of action of HLXL, correlating changes in biological markers of suppression of systemic inflammation with changes in clinical response

Official Title
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Dose Escalation Study Of Chinese Herbs In Osteoarthritis Of The Knee

Conditions
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Osteoarthritis of the Knee

Intervention / Treatment
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* Drug: HLXL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 40 years or above Diagnosis of OA of the knee of at least 6 months duration fulfilling American College of Rheumatology criteria Pain in at least one knee of at least moderate severity (Likert scale [none, mild, moderate, severe, extreme] or VAS pain score of at least 40 [0-100]) on most (at least 15) days of the previous 1 month Taking analgesic or nonsteroidal anti-inflammatory agents for control of pain Documented radiographic changes of osteoarthritis of the knee (Kellgren-Lawrence grade greater than or equal to 2 at the time of screening) Stable on arthritis medications for previous 1 month Willingness and ability, with help of a caregiver if necessary, to comply with treatment and follow-up procedures Use of effective contraception if woman of childbearing potential Signed consent statement Exclusion Criteria: Intra-articular (IA) corticosteroid injection of either knee within a 3 month interval immediately prior to baseline screening IA hyaluronates in either knee within the past 6 months Tidal lavage or arthroscopy of either knee within the past 12 months Medical condition, in the judgment of the examiner and/or study investigators, that may preclude safe participation in protocol or prevents completion of the study, such as: uncontrolled angina and/or congestive heart failure, severe chronic obstructive pulmonary disease, active treatment for cancer, major psychiatric disease, other severe systemic disease, or significant abnormalities on screening physical examination and laboratory tests that reveal clinically important abnormalities of hematological, cardiac, pulmonary, metabolic, renal, hepatic, gastrointestinal or other systems Use of any constituent herb in HLXL within the past 3 months Current use of Chinese herbs for arthritis Use of oral prednisone in the past 30 days Current use of anti-coagulants (coumadin, heparin, aspirin >325 mg per day). Use of any investigational drug within the past 30 days Inflammatory arthritis (e.g., rheumatoid or psoriatic arthritis) Currently participating in another intervention research study Unwilling to be randomized Plan to move residence away from the immediate area within the next 2 months Drug or alcohol abuse sufficient to hinder compliance with treatment or follow-up procedures Pregnant or lactating Exclusive use of a wheel chair Surgery in either knee in past one year

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Huo-Luo-Xiao-Ling<br>Active herb Huo-Luo-Xiao-Ling (HLXL) The subjects in the HLXL group received the medium dose of HLXL (10 capsules/day or 4,000mg/day) in the first 2 weeks to evaluate safety. If no adverse effects were observed, the dose was increased to 14 capsules per day (5,600 mg/day) for the subsequent 6 weeks. | Drug: HLXL<br>* Two daily dosages will be investigated. Huo-Luo-Xiao-Ling (HLXL) dose (10 capsules/day or 4,000mg/day) in the first 2 weeks to evaluate safety. If no adverse effects were observed, the dose was increased to 14 capsules per day (5,600 mg/ day) for the subsequent 6 weeks.<br>* Other names: Huo-Luo-Xiao-Ling (HLXL) Dan;|
| Placebo Comparator: Placebo<br>Placebo Huo-Luo-Xiao-Ling (HLXL): Subjects in the placebo group received an equal number of placebo capsule. | Drug: HLXL<br>* Two daily dosages will be investigated. Huo-Luo-Xiao-Ling (HLXL) dose (10 capsules/day or 4,000mg/day) in the first 2 weeks to evaluate safety. If no adverse effects were observed, the dose was increased to 14 capsules per day (5,600 mg/ day) for the subsequent 6 weeks.<br>* Other names: Huo-Luo-Xiao-Ling (HLXL) Dan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ‡Pain Normalized Score | ‡Pain normalized score and function normalized score are on a scale of 0-10, with 10 indicating extreme pain/difficulty related to knee arthritis and 0 indicating no pain/difficultly related to knee arthritis. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Function Normalized Score | Pain normalized score and function normalized score are on a scale of 0-10, with 10 indicating extreme pain/difficulty related to knee arthritis and 0 indicating no pain/difficultly related to knee arthritis. Overall normalized score is on a scale of 0-30, and is the sum of the pain, stiffness and function normalized scores (each on a scale of 0-10). | 8-Weeks | 
| Patient Global Assessment | §Patient Global Assessment is on a scale of 1-5, with 5 indicating excellent and 1 indicating poor (in response to the question Considering all the ways that your osteoarthritis of the knee affects you, how are you feeling today?) | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OA