Osteoarthritis of the Knee
Conditions
Keywords
OA
Brief summary
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
The specific aims of this project are: 1. 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, 2. 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, 3. To explore mechanisms of action of HLXL, correlating changes in biological markers of suppression of systemic inflammation with changes in clinical response
Interventions
DRUGHLXL
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.
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ‡Pain Normalized Score | 8 weeks | ‡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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Function Normalized Score | 8-Weeks | 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). |
| Patient Global Assessment | 8 weeks | §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?) |
Countries
United States
Participant flow
Recruitment details
Recruitment began in April 2007 and ended June 2011.
Pre-assignment details
2-week run-in period of intermediate-dose: 4,000 mg HLXL If no serious adverse events reported after 2 weeks, the high dose (5,600 mg/day) given for 6 additional weeks. Placebo: 14 #0 size gelatin capsules per day, orally, for 8 weeks. Intermediate-dose placebo (2-week run-in) (10 capsules daily) Highest-dose placebo (14 capsules daily)
Participants by arm
| Arm | Count |
|---|---|
| HLXL Active herb
HLXL: Two daily dosages will be investigated. The lowest dosage condition will be 10 capsules (4000 mg) daily for the first two weeks to evaluate safety, followed by an escalation to the 14 capsule condition (5,600 mg). Participants will be treated for 8 weeks. | 47 |
| Placebo Placebo
Placebo: Subjects in the placebo group received an equal number of placebo capsule. | 45 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 3 |
Baseline characteristics
| Characteristic | HLXL | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 60 years STANDARD_DEVIATION 9 | 60 years STANDARD_DEVIATION 9 | 60 years STANDARD_DEVIATION 9 |
| Sex: Female, Male Female | 32 Participants | 32 Participants | 64 Participants |
| Sex: Female, Male Male | 15 Participants | 13 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 47 | 5 / 45 |
| serious Total, serious adverse events | 0 / 47 | 0 / 45 |
Outcome results
Primary
‡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.
Time frame: 8 weeks
Population: Same as baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HLXL | ‡Pain Normalized Score | 3.3 Units on a scale | Standard Deviation 1.9 |
| Placebo | ‡Pain Normalized Score | 2.7 Units on a scale | Standard Deviation 1.7 |
p-value: 0.05t-test, 2 sided
Secondary
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).
Time frame: 8-Weeks
Population: Same as baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HLXL | Function Normalized Score | 3.6 Units on a scale | Standard Deviation 2 |
| Placebo | Function Normalized Score | 2.7 Units on a scale | Standard Deviation 1.4 |
Secondary
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?)
Time frame: 8 weeks
Population: Same as baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HLXL | Patient Global Assessment | 2.7 Units on a scale | Standard Deviation 1 |
| Placebo | Patient Global Assessment | 2.7 Units on a scale | Standard Deviation 1 |