Clinical trial NCT02543931: Curcuma Longa L in Rheumatoid Arthritis
Official title: Phase Ib Randomized, Double-Blind, Placebo-Controlled Study of Meriva in Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Keywords: turmeric
curcumin
curcuminoids
arthritis
methotrexate
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: Vanderbilt University
name: National Center for Complementary and Integrative Health (NCCIH)
name: National Institutes of Health (NIH)
First posted: 2015-09-07
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to find out whether turmeric dietary supplements that are available over the counter for general use in the United States are safe and useful when taken specifically for the treatment of rheumatoid arthritis (RA) and how the active principles in turmeric are broken down and metabolized by the body in individuals with RA.

Detailed description: A placebo-controlled, double-blind, three-arm Phase Ib clinical trial assessing two doses of a commercially available curcuminoid formulation with enhanced bioavailability vs. placebo in a rheumatoid arthritis (RA) population is proposed. The primary aim of this clinical planning study is to determine the dose-dependent tolerability of an enhanced bioavailability curcuminoid formulation in an RA population, including pharmacokinetic analyses, to inform the design of a future Phase II trial assessing the anti-inflammatory efficacy of curcuminoids in the treatment of RA. Secondarily, estimates of effect size for changes in known biomarkers of inflammation in RA will be determined.

Eligibility criteria: Inclusion Criteria:

* Inclusion Criteria

  * Diagnosis of RA (ACR 2010 criteria)
  * Age \> 18 years old
  * Active disease at screening visit as defined by:

    * Disease Activity Score \[DAS\]-28 (4)-erythrocyte sedimentation rate (ESR) \> 3.2, and
    * C reactive protein (CRP) \> 1.0 mg/dL or ESR \> 20.
  * Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Current treatment with any biologic agent (e.g. tumor necrosis factor (TNF) inhibitors: etanercept , infliximab, adalimumab; interleukin 1(IL-1) inhibitors: anakinra ; lymphocyte directed: abatacept, rituximab; and Janus kinase (JAK) inhibitors: tofacitinib).
* Past biologic use allowed if ended \> 3 months prior to randomization (\> 12 months for Rituximab)
* History of non-response to biologics.
* Disease-modifying anti-inflammatory agents (DMARDs), including methotrexate, hydroxychloroquine, sulfasalazine, and minocycline, will be allowed if stable for 1 month prior to randomization and unchanged throughout the study.
* Leflunomide, gold compounds, azathioprine, or cyclosporine will be exclusionary if used within the month prior to randomization.
* Oral Corticosteroid use \> 10 mg/d prednisolone or equivalent or parenteral corticosteroids of any dose will be exclusionary (1 month prior to randomization until final assessment visit).

  * Oral corticosteroids in low doses (\< 10 mg/d prednisone or equivalent) will be allowed if stable for 1 month prior to randomization and unchanged throughout the study).
  * Topical, inhaled, or intranasal steroids are not exclusionary
  * Past parenteral or oral (\> 10 mg/d prednisolone equivalent) corticosteroids allowed if not used within one month prior to randomization
* Non-steroidal anti-inflammatory drugs (NSAID) are exclusionary if used continuously or \> 3 doses in 7 days.

  o Enrollment will be allowed after a washout period of 1 week prior to randomization for use of \>3 doses In 7 days).
* Herbal supplements will be exclusionary.

  o Enrollment will be allowed after a washout period of 1 week prior to randomization). Patients will also be asked to minimize intake of curcuminoid-containing foods during the entire study period.
* History of positive skin test for tuberculosis (TB) without treatment.
* Systemic complications of RA (e.g. vasculitis).
* Recent surgery \< 1 month prior, or scheduled surgery \< 2 months after randomization
* History of malignancy, other than superficial basal or squamous cell carcinoma of the skin.
* History of, or concurrent, serious chronic infection.
* Women who are pre-menopausal (women with menses within the past 12-months) with an intact uterus must have a negative pregnancy test at screening and randomization, must be using a medically acceptable form of birth control, and may not be breast feeding.
* Worsening or uncontrolled end organ disease or intercurrent illness which, in the opinion of the investigator, may pose an added risk to the patient including, but not limited to, evidence of impaired renal function , hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or psychiatric disease.
* Acute or chronic liver disease, including Gilbert's syndrome.
* History of any atrioventricular (AV) nodal conduction defect or a P-R interval (interval between P wave QRS complex) and on ECG \> 0.2 sec.
* Use of illicit drugs or high alcohol consumption or current/recent (within past 5 years) history of drug or alcohol abuse.
* Treatment within 28 days of randomization with another investigational agent,
* Have a history of allergic reactions to turmeric, Meriva, or curcuminoids, including turmeric-containing foods such as curry or mustard.
* Inability or difficulty in swallowing oral medications, or any malabsorption condition.
* Inability to provide informed consent for any reason or to complete simple questionnaires.

Primary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: 1 week and 4 weeks
measure: Area under curve (AUC)
timeFrame: 0-24 h
measure: Cmax
timeFrame: 0-24h
measure: Tmax
timeFrame: 0-24h
measure: T1/2
timeFrame: 0-24h
measure: Cmax
timeFrame: 1 week and 4 week
Secondary outcomes:
measure: Changes in biomarkers of inflammation
timeFrame: 1 and 4 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona
state: Arizona
Study officials:
affiliation: The University of Arizona
name: Janet Funk, MD
role: PRINCIPAL_INVESTIGATOR
References: