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.  Must be able to understand and voluntarily sign an informed consent form, in the absence of dementia, defined as a Montreal Cognitive Assessment (MoCA) score ≥ 22 

2. Age 65 years and older, residing in the community or in an assisted-living facility 

3. Must be 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 

6. Serum IL-6 level ≥ 1.0 pg/mL obtained during screening period 

7. Must be able to understand and speak in English 

 

Exclusion Criteria

 

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 

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

9. Total bilirubin > 1.5 mg/dL

10. Use of any other experimental drug or therapy within 28 days of initial screening visit

11. History of tinnitus in the past 3 months

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 non steroidal 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