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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 11
- 试验地点
- 10
- 主要终点
- Change in Hemoglobin Level From Baseline to 6 Month Visit
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Salsalate (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Hemoglobin Level From Baseline to 6 Month Visit
时间窗: baseline; 6 months
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
次要结局
- Change in Self Reported Outcomes Measures as Reported by Short Form-36 (SF-36) Physical Component Score (PCS)(baseline; 6 months)
- Change in Markers of Inflammation(prior to study drug; 6 months)
- Change in Frailty Component Related to Fatigue/ Exhaustion(baseline; 6 months)
- Change in Self Reported Outcomes Measures as Reported by FACIT-AN Total Score(baseline; 6 months)
- Change in Frailty Component as Determined by the 4 Meter Walk Speed(baseline; 6 months)
- Assessment of Serum Biomarkers of Erthropoiesis(prior to study drug; 6 months)
- Change in Cognitive Outcome Measures-Trail Making Test Part B(baseline; 6 months)
- Change in Serum Hepcidin Levels(prior to study drug; 6 months)
- Change in Cognitive Outcome Measures as Determined by Speed of Processing(baseline; 6 months)
- Change in the Frailty Component as Determined by Self-reported Activity Level(baseline; 6 months)
- Change in Frailty Component as Determined by Grip Strength(baseline; 6 months)
- Change in Cognitive Outcome Measures as Determined by Composite Complex Attention/Executive Processing(baseline; 6 months)
- Change in Cognitive Outcome Measures as Determined by Composite Learning and Memory(baseline; 6 months)
研究者
Harvey Jay Cohen
Director, Professor and Chair
Duke University