Trial To Evaluate the Efficacy of Oral Salsalate in the Treatment of Older Adults With Unexplained Anemia
Condition: Anemia
MeSH terms: Anemia
Intervention: Salsalate; Placebo
Intervention description: Salsalate 750mg tablet 1 pill bid for one month followed by Salsalate 750mg tablets 2 pills (1500mg) twice a day for a further 5 months (total duration of treatment will be 6 months); Placebo tablet - one pill twice daily for one month, followed by 2 pills twice daily for a further 5 months. Total duration of treatment is 6 months
Intervention MeSH terms: Salicylic Acid; Salicylsalicylic acid; Salicylates
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 11.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: No
Keywords: anemia; unexplained anemia; elderly; geriatric; older adults; UAE; over 65; salsalate; PACTTE; pactee; aging; aged; old; older

Summary:

      The purpose of this study is to determine whether treatment of unexplained anemia in older
      adults and elevated inflammatory markers with oral salsalate can improve hemoglobin levels
      and improve physical activity and quality of life.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Understand and voluntarily sign an informed consent form

          -  Age 65 years and older, residing in the community or in an assisted-living facility

          -  Able to adhere to the study visit schedule and other protocol requirements

          -  Hemoglobin concentration ≥ 9.0 g/dL and < 11.5 g/dL for women and ≥ 9.0 to < 12.7 g/dL
             for men

          -  Unexplained anemia (See Appendix 2 for definitions of anemia diagnosis to determine
             anemia is unexplained)

          -  Serum IL-6 level ≥ 1.0 pg/mL obtained during screening period (performed at central
             laboratory).

          -  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:

          -  Red blood cell transfusions within the past 3 months

          -  Estimated glomerular filtration rate (eGFR) of < 30 ml/min (by abbreviated MDRD)

          -  Use of erythropoiesis stimulating agents (ESA) in the past 3 months

          -  Active infection defined as symptomatic, requiring active treatment (prophylaxis
             allowed) or hospitalized for > 24 hours primarily for infection within the past month

          -  Uncontrolled hypertension defined as diastolic blood pressure > 95 mm Hg or systolic
             blood pressure > 160 mm Hg on 2 separate occasions during screening period

          -  Distance on 6MWT above the median for age and sex adjusted population medians (see
             Table 4)

          -  Other primary uncorrected cause for anemia including:

               -  Known active inflammatory disease including auto-immune diseases (e.g., systemic
                  lupus erythematosis, rheumatoid arthritis, mixed connective tissue disease,
                  sarcoidosis, bronchiolitis obliterans, vasculitis, polymyalgia rheumatica,
                  temporal arteritis, inflammatory bowel disease or related diseases);

               -  Chronic active infection (e.g., HIV, viral hepatitis, tuberculosis,
                  osteomyelitis) or receiving therapy within the past 3 months for chronic
                  infection

               -  Acute infection within past 3 months (pneumonia, sepsis, bacteremia, prostatitis,
                  urosepsis, pyelonephritis, cholecystitis)

               -  Receipt of immunosuppressive therapy in the past 2 years including prednisone
                  except for topical therapy

               -  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.

               -  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

          -  Elevated AST or ALT ≥ 2x upper limit of normal

          -  Use of any other experimental drug or therapy within 28 days of initial screening
             visit

          -  History of moderate tinnitus affecting instrumental activities of daily activities in
             the past 3 months

          -  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.

          -  Elevated thyroid stimulating hormone (TSH), or other signs of hypothyroid condition.
             Patients on a stable dose of thyroid replacement are eligible, providing TSH is not
             elevated.

          -  Seizure disorder for which phenytoin is used for treatment.

          -  Hypersensitivity to salsalate, salicylic acid, or acetylsalicylic acid

          -  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

          -  Dementia defined as the inability to independently provide informed consent and a
             Montreal Cognitive Assessment (MoCA) score < 22