Clinical trial NCT01506726: Trial To Evaluate the Efficacy of Oral Salsalate in the Treatment of Older Adults With Unexplained Anemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Anemia
Keywords: anemia
unexplained anemia
elderly
geriatric
older adults
UAE
over 65
salsalate
PACTTE
pactee
aging
aged
old
older
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2012-01-10
Enrollment: 11
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: There is well-defined morbidity and mortality associated with anemia in the elderly and the increasing proportion of elderly adults underscores the population's attributable risk of anemia. As a potentially modifiable factor, an urgent need exists to delineate the impact of anemia correction in the elderly. The Partnership for Anemia: Clinical and Translational Trials in the Elderly (PACTTE) consortium has been created to focus on treatment strategies for anemia in elderly patients. The data presented in this protocol provides a compelling rationale to evaluate the impact of an anti-inflammatory (Salsalate) in older anemic adults with elevated serum iL-6 levels.

Subjects will be 65 years or older adults with unexplained anemia and a elevated serum iL-6 ≥ 1.0 pg/mL.

Subjects will receive 750mg of salsalate or matching placebo (one pill) twice a day (am and pm) for one month. After one month the dose will be increased to 1500mg (2 pills) twice a day (am and pm) if the 750mg dose was tolerated for a further 5 months (for a total of 6 months)

The primary endpoint is to assess whether salsalate improves hemoglobin levels from baseline to 6 month visit.

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

Primary outcomes:
measure: Change in Hemoglobin Level From Baseline to 6 Month Visit
timeFrame: baseline; 6 months
Secondary outcomes:
measure: Change in Markers of Inflammation
timeFrame: prior to study drug; 6 months
measure: Assessment of Serum Biomarkers of Erthropoiesis
timeFrame: prior to study drug; 6 months
measure: Change in Serum Hepcidin Levels
timeFrame: prior to study drug; 6 months
measure: Change in Cognitive Outcome Measures-Trail Making Test Part B
timeFrame: baseline; 6 months
measure: Change in Frailty Component Related to Fatigue/ Exhaustion
timeFrame: baseline; 6 months
measure: Change in Cognitive Outcome Measures as Determined by Speed of Processing
timeFrame: baseline; 6 months
measure: Change in Cognitive Outcome Measures as Determined by Composite Complex Attention/Executive Processing
timeFrame: baseline; 6 months
measure: Change in Cognitive Outcome Measures as Determined by Composite Learning and Memory
timeFrame: baseline; 6 months
measure: Change in Self Reported Outcomes Measures as Reported by Short Form-36 (SF-36) Physical Component Score (PCS)
timeFrame: baseline; 6 months
measure: Change in Self Reported Outcomes Measures as Reported by FACIT-AN Total Score
timeFrame: baseline; 6 months
measure: Change in the Frailty Component as Determined by Self-reported Activity Level
timeFrame: baseline; 6 months
measure: Change in Frailty Component as Determined by Grip Strength
timeFrame: baseline; 6 months
measure: Change in Frailty Component as Determined by the 4 Meter Walk Speed
timeFrame: baseline; 6 months
measure: Change in Markers of Inflammation
timeFrame: prior to study drug; 6 months
measure: Assessment of Serum Biomarkers of Erthropoiesis
timeFrame: prior to study drug; 6 months
Other outcomes:
measure: Change in the 6 Minute Walk Test (6MWT) Distance.
timeFrame: baseline; 6 months
measure: Association Between Change in Hemoglobin and Change in Markers of Inflammation.
timeFrame: prior to study drug; 6 months
Locations:
city: Summerfield
country: United States
facility: Lakeview Medical Research
state: Florida
city: Savannah
country: United States
facility: St Joseph's/Candler Health System
state: Georgia
city: Chicago
country: United States
facility: University of Illinois, Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Lexington
country: United States
facility: Central Kentucky Research Associates
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University Geriatrics Center
state: Maryland
city: Cleveland
country: United States
facility: Case Western Reserve University Medical Center
state: Ohio
city: Columbia
country: United States
facility: Clinical Research Solutions
state: Tennessee
city: Franklin
country: United States
facility: Clinical Research Solutions
state: Tennessee
city: Smyrna
country: United States
facility: Clinical Research Solutions
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah School of Medicine
state: Utah
city: Falls Church
country: United States
facility: Institute for Advanced Studies in Aging (IASIA)
state: Virginia
Study officials:
affiliation: Institute for Advanced Studies in Aging (IASIA)
name: William Ershler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Stanley Schrier, MD
role: STUDY_CHAIR
affiliation: Johns Hopkins University
name: Jeremy Walston, MD
role: PRINCIPAL_INVESTIGATOR
References: