Trial To Evaluate the Efficacy of Oral Salsalate in the Treatment of Older Adults With Unexplained Anemia
This study is currently recruiting participants.
Verified December 2012 by Duke University
Sponsor:
Harvey Jay Cohen
Collaborator:
Information provided by (Responsible Party):
Harvey Jay Cohen, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01506726
First received: January 6, 2012
Last updated: December 12, 2012
Last verified: December 2012
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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 2014 |
| Estimated Primary Completion Date: | October 2014 (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:
|
|
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 70 years or older adults with unexplained anemia and a elevated serum iL-6 >2.5pg/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: | 70 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Understand and voluntarily sign an informed consent form
- Age 70 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 ≥ 2.5 pg/mL obtained during screening period (performed at central laboratory).
- Must be able to understand and speak in English
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
- Total bilirubin > 1.5 mg/dL
- Use of any other experimental drug or therapy within 28 days of initial screening visit
- History of tinnitus 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: Kerstin McHutchison, RN | 919 886 2825 | kerstin.newland@duke.edu |
| Contact: Carrie Elliott, M.Ed | 919 668 8021 | carrie.elliott@duke.edu |
Locations
| United States, California | |
| Stanford University Medical Center | Recruiting |
| Palo Alto, California, United States, 94305 | |
| Contact: Evelyn Castillo 650-736-1836 evelyn1@stanford.edu | |
| Principal Investigator: Michaela Liedtke, MD | |
| Sub-Investigator: Stanley Schrier, 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, MD | |
| United States, Maryland | |
| Johns Hopkins University Geriatrics Center | Not yet recruiting |
| Baltimore, Maryland, United States, 21224 | |
| Contact: Ora White 410-614-0740 owhite1@jhmi.edu | |
| Principal Investigator: Jeremy Walston, MD | |
| United States, Ohio | |
| Case Western Reserve University Medical Center | Recruiting |
| Cleveland, Ohio, United States, 44106 | |
| Contact: Nyesha Smith 216-286-6535 nyesha.smith@uhhospitals.org | |
| Principal Investigator: Nathan Berger, MD | |
| United States, Utah | |
| University of Utah School of Medicine | Not yet recruiting |
| Salt Lake City, Utah, United States, 84132 | |
| Contact: Jasmine Lee 801-581-3707 jasmine.lee@hsc.utah.edu | |
| Principal Investigator: Neeraj Agarwal, 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: | December 12, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Duke University:
|
anemia unexplained anemia elderly geriatric older adults UAE over 70 |
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 May 19, 2013