Trial To Evaluate the Efficacy of Oral Salsalate in the Treatment of Older Adults With Unexplained Anemia

Anemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01506726
• Other study ID #: Pro00033852
• Secondary ID: U01AG034661
• Status: Terminated
• Phase: Phase 2
• First received: January 6, 2012
• Last updated: October 26, 2015
• Start date: March 2012
• Est. completion date: November 2014

Study information

• Verified date: October 2015
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: November 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia

Intervention

Drug:
• Salsalate
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
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

Locations

Country	Name	City	State
United States	Johns Hopkins University Geriatrics Center	Baltimore	Maryland
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of Illinois, Chicago	Chicago	Illinois
United States	Case Western Reserve University Medical Center	Cleveland	Ohio
United States	Clinical Research Solutions	Columbia	Tennessee
United States	Institute for Advanced Studies in Aging (IASIA)	Falls Church	Virginia
United States	Clinical Research Solutions	Franklin	Tennessee
United States	Central Kentucky Research Associates	Lexington	Kentucky
United States	University of Utah School of Medicine	Salt Lake City	Utah
United States	St Joseph's/Candler Health System	Savannah	Georgia
United States	Clinical Research Solutions	Smyrna	Tennessee
United States	Lakeview Medical Research	Summerfield	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Harvey Jay Cohen	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To Assess Whether Oral Salsalate Improves Performance in the 6 Minute Walk Test (6MWT)	To assess the impact of treatment of anemia with oral salsalate will improve 6 minute walk test (6MWT) distance from baseline to 6 months as measured in meters and centimeters.	6 months	No
Other	Change in Markers of Inflammation	To assess whether treatment of anemia with oral salsalate reduces markers of inflammation from baseline to 6 months. Inflammatory markers to be measured are iL-6, Tumor Necrosis Factor alpha Receptor1 (TNF-R1), and C-reactive protein (CRP) in anemia subjects	6 months	No
Primary	Change in Hemoglobin Level From Baseline to 6 Month Visit	To test whether the administration of oral salsalate to a subset of elderly subjects with unexplained anemia (UAE) and high interleukin (IL-6) levels will improve hemoglobin level	6 months	No
Secondary	Assessment in Inflammatory Proteins	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	6 months	No
Secondary	Assessment of Serum Biomarkers of Erthropoiesis	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	6 months	No
Secondary	Reduction in Serum Hepcidin Levels	To assess whether salsalate will reduce serum hepcidin levels and whether such a change is proportional to the decline in IL-6 levels	6 months	No
Secondary	Change in Cognitive Outcome Measures	To quantify the impact salsalate treatment on the following functional and self-report outcome measures as assessed by the geriatric evaluation panel (GEP) consisting of the following:Trail-Making Test and CogState cognitive tests; Short-Form 36 and physical component score (PCS) subscale; Functional Assessment in Chronic Illness Therapy-Anemia (FACIT-An).	6 months	No
Secondary	Change in Self Reported Outcomes Measures	To quantify the impact of anemia treatment with oral salsalate on self-reported outcomes measures by change in Short Form 36 (SF-36) 8 scale scores and the physical component score and FACIT-AN 5 subscale scores, a trial outcome index and a total score	6 months	No
Secondary	Change in Frailty Index	To quantify the impact of anemia treatment with oral salsalate on change in the frailty index as measured by change in self-reported exhaustion score, self-reported activity level score, Grip-strength (kgs) and 4 meter walk speed (meters/sec)	6 months	No

External Links

•   PACTTE Consortium Website