Curcuma Longa L in Rheumatoid Arthritis

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.

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.

- On methotrexate (MTX) treatment:

- for at least 3 months prior to screening,

- with stable dose (10-25 mg/week) for at least 28 days prior to screening to
remain unchanged during study.

- 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.

- Non-MTX disease-modifying anti-inflammatory agents (DMARDs), including
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.