Curcuma Longa L in Rheumatoid Arthritis (CLaRA)

Phase Ib Randomized, Double-Blind, Placebo-Controlled Study of Meriva in Rheumatoid Arthritis

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.

Study Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: placebo; Drug: Meriva

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • The University of Arizona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will take 4 placebo capsules twice a day for one month	Drug: placebo; Placebo capsules containing inert ingredients; Other Names: inactive capsule
Experimental: Meriva, low dose; Participants will take 4 Meriva-250mg capsules twice a day for one month	Drug: Meriva; Meriva is an enhanced-bioavailability, curcuminoid-enriched turmeric dietary supplement that is sold over the counter in the United States and other countries.; Other Names: turmeric, enhanced bioavailability
Experimental: Meriva, high dose; Participants will take 4 Meriva-500mg capsules twice a day for one month	Drug: Meriva; Meriva is an enhanced-bioavailability, curcuminoid-enriched turmeric dietary supplement that is sold over the counter in the United States and other countries.; Other Names: turmeric, enhanced bioavailability

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability		1 week and 4 weeks
Area under curve (AUC)	Following first dose.	0-24 h
Cmax	Following first dose.	0-24h
Tmax	Following first dose.	0-24h
T1/2	Following first dose.	0-24h
Cmax	Plasma concentration after multiple daily dosings	1 week and 4 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in biomarkers of inflammation	Changes from baseline in blood levels of ESR and C reactive protein will be determined after 1 and 4 weeks of treatment	1 and 4 weeks

Collaborators and Investigators

• Sponsor: University of Arizona
• Collaborators: National Institutes of Health (NIH); Vanderbilt University; National Center for Complementary and Integrative Health (NCCIH)
• Investigators: Principal Investigator: Janet Funk, MD, The University of Arizona

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): September 1, 2017

Study Registration Dates

• First Submitted: August 6, 2015
• First Submitted That Met QC Criteria: September 3, 2015
• First Posted (Estimate): September 7, 2015

Study Record Updates

• Last Update Posted (Estimate): November 30, 2016
• Last Update Submitted That Met QC Criteria: November 28, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: methotrexate; arthritis; curcumin; turmeric; curcuminoids
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: 1501627690; R34AT007837 (U.S. NIH Grant/Contract)