A Randomized, Double Blind, Placebo Controlled Pilot Trial of Oral Salsalate in the Treatment of the Subset of Unexplained Anemia in Elderly Patients with Elevated Interleukin-6

Overview

Status: Recruiting
Keywords: Salsalate , Anemia , Elderly
IRB Number: 00056709
Specialty: Geriatrics
Sub Specialties:

Brief Summary

 

To test whether the administration of oral salsalate to a subset of elderly subjects with unexplained anemia (UAE) and high interleukin-6 (IL-6) levels will improve hemoglobin level.

Detailed Description

• To assess whether oral salsalate improves performance in the 6 minute walk test (6MWT) • To assess whether oral salsalate reduces markers of inflammation including IL-6, Tumor Necrosis Factor  Receptor1 (TNF-R1), and C-reactive protein (CRP) in UAE subjects • To assess whether oral salsalate improves serum biomarkers of erythropoiesis by increasing erythropoietin (Epo) and decreasing growth differentiation factor-15 (GDF-15) in UAE subjects • To examine whether there is an association between improved hemoglobin level and reduced inflammatory profile in subjects with UAE treated with salsalate • To assess whether salsalate will reduce serum hepcidin levels and whether such a change is proportional to the decline in IL-6 levels • To quantify the impact of salsalate treatment on the following functional and self-report outcome measures as assessed by the geriatric evaluation panel (GEP) consisting of the following: o Trail-Making Test and CogState cognitive tests o Short-Form 36 and physical component score (PCS) subscale o Functional Assessment in Chronic Illness Therapy-Anemia (FACIT-An) o Four components of the frailty index: • Grip strength • 4 meter walk speed • Self-reported exhaustion • Self-reported activity level

Principal Investigator: Mark Supiano
Department: Geriatrics
Co Investigator:

Contact Information

Name:Joshua Shimizu
Phone: 801-587-7759
Email: joshua.shimizu@hsc.utah.edu

Inclusion Criteria

 

1. Understand and voluntarily sign an informed consent form
2. Age 65 years and older, residing in the community or in an assisted-living facility
3. Able to adhere to the study visit schedule and other protocol requirements
4. Hemoglobin concentration ≥ 9.0 g/dL and < 11.5 g/dL for women and ≥ 9.0 to < 12.7 g/dL for men
5. Unexplained anemia (See Appendix 2 for definitions of anemia diagnosis to determine anemia is unexplained)
6. Serum IL-6 level ≥ 1.0 pg/mL obtained during screening period (performed at central laboratory).
7. Must be able to understand and speak in English; or Spanish speaking subjects who do not speak English may be enrolled per local IRB process and approval, provided the
site has appropriate bilingual study staff.

Exclusion Criteria

1. Red blood cell transfusions within the past 3 months
2. Estimated glomerular filtration rate (eGFR) of < 30 ml/min (by abbreviated MDRD)
3. Use of erythropoiesis stimulating agents (ESA) in the past 3 months
4. Active infection defined as symptomatic, requiring active treatment (prophylaxis allowed) or hospitalized for > 24 hours primarily for infection within the past month
5. Uncontrolled hypertension defined as diastolic blood pressure > 95 mm Hg or systolic blood pressure > 160 mm Hg on 2 separate occasions during screening period
6. Distance on 6MWT above the median for age and sex adjusted population medians (see Table 4)
7. Other primary uncorrected cause for anemia including:
a. Known active inflammatory disease including autoimmune diseases (e.g., systemic lupus erythematosis,
rheumatoid arthritis, mixed connective tissue disease, sarcoidoisis, bronchiolitis obliterans, vasculitis,
polymyalgia rheumatica, temporal arteritis, inflammatory bowel disease or related diseases);
b. Chronic active infection (e.g., HIV, viral hepatitis, tuberculosis, osteomylelitis) or receiving therapy within
the past 3 months for chronic infection
c. Acute infection within past 3 months (pneumonia, sepsis, bacteremia, prostatitis, urosepsis, pyelonephritis, cholecystitis)
d. Receipt of immunosuppressive therapy in the past 2 years including prednisone except for topical therapy
e. Any cancer (aside from non-melanoma skin cancer) in
the past 2 years or on therapy for cancer. In addition,
prostate cancer will be excluded if patients have
metastatic disease, have had prostatectomy within the
prior 6 months, have ever received external beam
radiation therapy or brachytherapy, or have received
androgen deprivation therapy in the prior 24
months. Subjects with a history of any other form of
cancer will likewise be excluded if they have received
any radiation or chemotherapy in the prior 24 months.
f. Fecal Occult Blood Test positivity in the past 3 years,
Gastrointestinal bleeding in past 3 years and history of
peptic ulcer w/ evidence of bleeding
8. Elevated AST or ALT ≥ 2x upper limit of normal
10. Use of any other experimental drug or therapy within 28 days
of initial screening visit
11. History of moderate tinnitus affecting instrumental activities of
daily activities in the past 3 months (i.e., grade 2 or more by
Common Toxicity Criteria for Adverse Events)
12. Current use of acetylsalicylic acid (aspirin) in doses greater
than 82 mg/day in the past 3 months. Subjects will also be
ineligible if they consume or are expected to consume nonsteroidal
anti-inflammatory drugs (NSAIDs), corticosteroids,
methotrexate, furosemide or anticoagulants during the course
of this study.
13. Elevated TSH, or other signs of hypothyroid condition.
Patients on a stable dose of thyroid replacement are eligible,
providing TSH is not elevated.
14. Seizure disorder for which phenytoin is used for treatment.
15. Hypersensitivity to salsalate, salicylic acid, or acetylsalicylic
acid
16. History of transient ischemic attacks (TIA), cerebral vascular
accident, a clinical diagnosis of angina or myocardial
infarction, any coronary interventions (PCI, Bypass, Stent
placement) within the prior 12 months to reduce the risk of
subject requiring aspirin therapy during the trial
17. Dementia defined as the inability to independently provide
informed consent and a Montreal Cognitive Assessment
(MoCA) score < 22