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

This study is currently recruiting participants.
Verified April 2014 by Duke University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Harvey Jay Cohen, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01506726
First received: January 6, 2012
Last updated: April 16, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Anemia
Unexplained Anemia
Drug: Salsalate
Drug: Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Improvement in hemoglobin level from baseline to 6 month visit [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine whether the administration of oral salsalate to older adults with unexplained anemia (UAE) and elevated inflammatory markers (iL-6) over a 6 month period leads to improvement in hemoglobin levels. The primary endpoint is change in hemoglobin level from baseline to 6 months.


Secondary Outcome Measures:
  • Improvement in 6 minute walk test [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.

  • Change in markers of inflammation [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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

  • Improvement in serum biomarkers of erythropoiesis [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To assess whether treatment of anemia with oral salsalate improves biomarkers of erythropoiesis by measuring erythropoietin levels and growth differentiation factor-15 (GDF-15) from baseline to 6 months

  • Examination of association between hemoglobin and reduced inflammatory profile [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To examine whether there is an association between hemoglobin levels and reduced inflammatory profile as measured by iL-6, TNF-R1, CRP levels

  • Reduction in serum hepcidin levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To assess whether treatment with oral salsalate will reduce serum hepcidin levels as measured from baseline to 6 months and whether this change is proportional to the decline in iL-6 levels

  • Change in cognitive outcome measures [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To quantify the impact of anemia treatment with oral salsalate on cognitive outcomes based on the Trail Making Test (TMT) Part A and B as measured by seconds per completed circle, and the Cogstate Research computerized testing system to yield 9 test scores that will be used in the analyses of the secondary cognitive outcomes

  • Change in self reported outcomes measures [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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

  • Change in frailty index [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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)


Estimated Enrollment: 60
Study Start Date: March 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active drug - oral salsalate
Subjects randomized to active drug arm will receive 750mg of salsalate (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 (if the 750mg dose was tolerated) for a further 5 months. Total treatment time is 6 months.
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)
Other Names:
  • salicylate
  • salicylate acid
Placebo Comparator: Placebo Arm
Subjects randomized to the placebo arm will receive a matching placebo pill (one pill) twice a day (am and pm) for one month. After one month the dose will be increased to 2 matching placebo pills twice a day (if the one pill dose was tolerated) for a further 5 months. Total treatment time is 6 months.
Drug: 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
Other Name: Placebo tablet

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

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01506726

Contacts
Contact: Sandra Tourt-Uhlig, RN, MSN 919 681 6757 sandra.tourtuhlig@duke.edu
Contact: Carrie Elliott, M.Ed., RN 919 668 8021 carrie.elliott@duke.edu

Locations
United States, California
Novo Research, Inc. Withdrawn
Modesto, California, United States, 95350
Stanford University Medical Center Withdrawn
Palo Alto, California, United States, 94305
United States, Florida
Lakeview Medical Research Recruiting
Summerfield, Florida, United States, 34491
Contact: Pamela Ervin    352-693-2354    pervin@lakeviewmedicalresearch.com   
Principal Investigator: Khai Chang, MD         
United States, Georgia
St Joseph's/Candler Health System Recruiting
Savannah, Georgia, United States, 31405
Contact: Barbara Lassiter    912-819-6386    lassiterb@sjchs.org   
Principal Investigator: Mohammad Masroor, MD         
United States, Illinois
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Contact: Peggy Green    773-702-0267    mgreen@medicine.bsd.uchicago.edu   
Principal Investigator: Andrew Artz, MD         
University of Illinois, Chicago Recruiting
Chicago, Illinois, United States, 60612
Contact: Lani Krauz    312-413-0242    lignacio@uic.edu   
Principal Investigator: Donald Juravich, DO         
United States, Kentucky
Central Kentucky Research Associates Recruiting
Lexington, Kentucky, United States, 40509
Contact: Crystal Reed    859-264-8999    creed@ckrainc.com   
Principal Investigator: James L Borders, MD         
United States, Maryland
Johns Hopkins University Geriatrics Center Recruiting
Baltimore, Maryland, United States, 21224
Contact: Ora White    410-550-9017    owhite1@jhmi.edu   
Principal Investigator: Jeremy Walston, MD         
United States, Ohio
Case Western Reserve University Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Jennifer Sustin, MS    216-286-6656    jennifer.sustin@uhhospitals.org   
Principal Investigator: Nathan Berger, MD         
United States, Tennessee
Clinical Research Solutions Recruiting
Columbia, Tennessee, United States, 38401
Contact: Beverly Harris    931-698-6699    bharris@crssites.com   
Principal Investigator: Shawn Gentry, MD         
Clinical Research Solutions Recruiting
Franklin, Tennessee, United States, 37064
Contact: William Adamson    615-577-4017    wadamson@crssites.com   
Principal Investigator: Alex Slandzicki, MD         
Clinical Research Solutions Recruiting
Smyrna, Tennessee, United States, 37167
Contact: Ashley Adamson, MA    615-216-4823    aadamson@crssites.com   
Principal Investigator: Sadia Dar, MD         
United States, Utah
University of Utah School of Medicine Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Brianne Glenn    801-587-7525    Brianne.Glenn@hsc.utah.edu   
Principal Investigator: Mark Supiano, MD         
United States, Virginia
Institute for Advanced Studies in Aging (IASIA) Recruiting
Falls Church, Virginia, United States, 22042
Contact: Irene Flores, RN    703-241-1010 ext 241    iflores@iasia.org   
Principal Investigator: William Ershler, MD         
Sponsors and Collaborators
Harvey Jay Cohen
Investigators
Principal Investigator: William Ershler, MD Institute for Advanced Studies in Aging (IASIA)
Study Chair: Stanley Schrier, MD Stanford University
Principal Investigator: Jeremy Walston, MD Johns Hopkins University
  More Information

Additional Information:
No publications provided

Responsible Party: Harvey Jay Cohen, Director, Professor and Chair, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01506726     History of Changes
Other Study ID Numbers: Pro00033852, U01AG034661
Study First Received: January 6, 2012
Last Updated: April 16, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Duke University:
anemia
unexplained anemia
elderly
geriatric
older adults
UAE
over 65
salsalate
PACTTE
pactee
aging
aged
old
older

Additional relevant MeSH terms:
Anemia
Hematologic Diseases
Salicylates
Sodium Salicylate
Salicylsalicylic acid
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 17, 2014