Dose Escalation Study Of Chinese Herbs In Osteoarthritis Of The Knee (TCM-OAK)

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.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis of the Knee
• Intervention / Treatment: Drug: HLXL

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

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21207
      • University of Maryland Center for Integrative Medicine Kernan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Huo-Luo-Xiao-Ling; 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; 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.; Other Names: Huo-Luo-Xiao-Ling (HLXL) Dan
Placebo Comparator: Placebo; Placebo Huo-Luo-Xiao-Ling (HLXL): Subjects in the placebo group received an equal number of placebo capsule.	Drug: HLXL; 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.; Other Names: Huo-Luo-Xiao-Ling (HLXL) Dan

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: National Center for Complementary and Integrative Health (NCCIH)
• Investigators: Principal Investigator: Brian M. Berman, MD, University of Maryland, Baltimore

Publications and helpful links

General Publications

• Lao L, Hochberg M, Lee DYW, Gilpin AMK, Fong HHS, Langenberg P, Chen K, Li EK, Tam LS, Berman B. Huo-Luo-Xiao-Ling (HLXL)-Dan, a Traditional Chinese Medicine, for patients with osteoarthritis of the knee: a multi-site, randomized, double-blind, placebo-controlled phase II clinical trial. Osteoarthritis Cartilage. 2015 Dec;23(12):2102-2108. doi: 10.1016/j.joca.2015.06.007. Epub 2015 Jun 20.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: September 17, 2008
• First Submitted That Met QC Criteria: September 17, 2008
• First Posted (Estimate): September 18, 2008

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 6, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: OA
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: HP-00040954; U19AT003266-01 (U.S. NIH Grant/Contract)