Dose Escalation Study Of Chinese Herbs In Osteoarthritis Of The Knee

NCT ID: NCT00755326

Last Updated: 2020-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2010-07-31

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

Conditions

Osteoarthritis of the Knee

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

HLXL

Intervention Type: DRUG

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.

Placebo

Placebo Huo-Luo-Xiao-Ling (HLXL): Subjects in the placebo group received an equal number of placebo capsule.

Group Type: PLACEBO_COMPARATOR

HLXL

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Huo-Luo-Xiao-Ling (HLXL) Dan

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Center for Complementary and Integrative Health (NCCIH)

NIH

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Brian Berman

Director, Center for Integrative Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Brian M. Berman, MD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Locations

University of Maryland Center for Integrative Medicine Kernan Hospital

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26099553 (View on PubMed)

Other Identifiers

U19AT003266-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HP-00040954

Identifier Type: -

Identifier Source: org_study_id