Trial Outcomes & Findings for Trial To Evaluate the Efficacy of Oral Salsalate in the Treatment of Older Adults With Unexplained Anemia (NCT NCT01506726)

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

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

To assess whether oral salsalate reduces markers of inflammation including IL-6 and Tumor Necrosis Factor Receptor1 (TNF-R1) in UAE subjects. Change in the marker from prior to study drug to 6 months.

To assess whether oral salsalate improves serum biomarkers of erythropoiesis by increasing erythropoietin (Epo) in UAE subjects. Change in the Epo from prior to study drug to 6 months.

To compare the change in serum hepcidin levels between treatment groups and whether such a change is proportional to the decline in IL-6 levels. Change in the hepcidin from prior to study drug to 6 months. Positive changes represent increases in hepcidin levels and negative changes represent decreases.

To quantify the impact of anemia treatment by salsalate on cognitive outcomes based on the Trail Making Test (TMT) Part B as measured by subjects drawing a line from 25 circled numbers to letters in 300 seconds. The change in seconds per completed circle from baseline to month 6.

Subjective fatigue/exhaustion: If any of the following three criteria are met, the patient will be classified as frail for fatigue/exhaustion: 1. "In the past month, on average, have you been feeling unusually tired during the day?" is answered "yes" and indicated as "all of the time" or "most of the time." 2. "In the past month, on average, have you felt unusually weak?" is answered "yes" and indicated as "all of the time" or "most of the time." 3. Energy level on a scale of 0 (no energy) to 10 (most energy) reported as ≤ 3. If the subject answers YES to any of the above noted 3 questions, then they are classified as FRAIL. The change in frailty for fatigue/ exhaustion is defined as changing from frail at baseline to not frail at month 6 as reported by the subject.

To quantify the impact of anemia treatment by salsalate on cognitive outcomes based on speed of processing was derived using the z-scores of the following three tests: (1) TMT Part A seconds per completed circle, (2) simple reaction time from the CogState Detection Task, and (3) choice reaction time from the CogState Identification Task. The composite score for a subject at each time point was defined as the mean of the Z-scores for the three tests at the time point. For each subject, the Z-score for each test at time point was derived by subtracting the subject's score at the time point from the overall baseline mean of the test and then dividing by the overall baseline standard deviation of the test. Positive z-scores indicate a better performance compared to the baseline average.The change in the Z-score from baseline to month 6.

To quantify the impact of anemia treatment by salsalate on cognitive outcomes based on Complex attention/executive processing was derived using the z-scores of the following three tests: (1) TMT Part B seconds per completed circle, (2) time score from the CogState One Back Task, and (3) accuracy score from the CogState One Back Task. The composite score for a subject at each time point was defined as the mean of the Z-scores for the three tests at the time point. For each subject, the Z-score for each test at time point was derived by subtracting the overall baseline mean of the test from the subject's score at the time point (accuracy score) or by subtracting the subject's score at the time point from the overall baseline mean of the test (TMT and time score) and then dividing by the overall baseline standard deviation of the test. Positive z-scores indicate a better performance compared to the baseline average. The change in the Z-score from baseline to month 6.

To quantify the impact of anemia treatment by salsalate on cognitive outcomes based on Learning and memory was derived using the z-scores of the following three tests: (1) CogState ISL immediate recall score (total score from three learning trials), (2) CogState ISL immediate recall score from the first learning trial, and (3) CogState ISL delayed recall scores. The composite score for a subject at each time point was defined as the mean of the Z-scores for the three tests at the time point. For each subject, the Z-score for each test at time point was derived by subtracting the overall baseline mean of the test from the subject's score at the time point and then dividing by the overall baseline standard deviation of the test. Positive z-scores indicate a better performance compared to the baseline average. The change in the Z-score from baseline to month 6.

To quantify the impact of anemia treatment by salsalate on self-reported outcomes measures by change in SF36 physical component score. The SF-36 form identifies self-report physical function and global measure of quality of life and is a multi-purpose, short-form health survey consisting of 36 questions. The Physical Component Summary (PCS) is a subscale of the SF-36 that correlates with physical health domains of the SF-36 ( Physical Function, Role-Physical, and Bodily Pain). The change is calculated and compared from baseline to 6 months. The SF-36 PCS score is a norm based sore with a mean of 50 and standard deviation of 10 where results above and below 50 are above and below the average, respectively, in the 2009 general US population.

To quantify the impact of anemia treatment by salsalate on self -reported outcomes measures by subjects answering 47 questions for patients with anemia and or fatigue. This test detects self-report functional changes and QoL. Change from baseline to 6 months. Scores range from 0-188 with higher scores indicating better function.

To quantify the impact of anemia treatment by salsalate on change in the frailty as measured by change in self-reported activity level. Frailty for activity level is classified by subjects responses to 6physical activity questions on the short version of the Minnesota Leisure Time Activity Questionnaire , were related to walking for exercise, moderately strenuous outdoor chores, dancing, bowling, and regular exercise. The Women's Health And Aging Study (WHAS) scoring algorithm was used to define frailty for self-reported activity level. The answers to these questions were used to calculate kilocalories (Kcals) per week, using the WHAS algorithm, which is further satisfied by by gender. For men, Kcals \< 128 per week is frail. For women, Kcals \< 90 per week is frail. This is a categorical measurement of yes or no. The outcome is the number of participants who were classified as "frail" at baseline and changed to "not frail" at 6 months.

To quantify the impact of anemia treatment by salsalate on change in the frailty as measured by change in grip strength. Subjects squeeze the grip strength machine 3 times with each hand. For the frailty outcome the maximum grip strength from the dominant hand is used. (change from frail at baseline to not frail at 6 months). Grip strength is stratified by gender and BMI. For men with (BMI \<= 24 and a grip strength (GS) \<= 29) or (BMI 24.1-28 and grip strength \<= 30) or (BMI \>28 and a grip strength \<= 32) were classified as "frail". For women with (BMI \<= 23 and a grip strength of \<= 17) or (BMI 23.1-26 and a GS \<= 17.3) or (BMI 26.1-29 and a GS \<= 18) or (BMI \> 29 and a GS \<= 21) were classified as "frail".The outcome is the number of participants who were classified as "frail" at baseline and changed to "not frail" at 6 months.

To quantify the impact of anemia treatment by salsalate on change in the speed of the 4 meter walk speed. Subjects are asked to walk as fast as they can for 4 meters. Frailty was determined by the subject's speed. (change from frail at baseline to not frail at 6 months). 4 m walking speed is stratified by gender and height. For men, (height of \<= 173 cm and a walking speed of \<= 0.65 meter/sec) or a (height \> 173, \<= .76 meter/sec) were classified as "frail". For women, (height of \<= 159 cm and a walking speed of \<=.65 meter/sec) or (height \>159 cm \<= 0.76 meter/sec) were classified as "frail".The outcome is the number of participants who were classified as "frail" at baseline and changed to "not frail" at 6 months.

To assess whether oral salsalate reduces C-reactive protein (CRP) in UAE subjects. Change in the CRP from prior to study drug to 6 months.

To assess whether oral salsalate improves serum biomarkers of erythropoiesis by decreasing growth differentiation factor-15 (GDF-15) in UAE subjects. Change in the GDF-15 from prior to study drug to 6 months.

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.

To examine whether there is an association between change in hemoglobin and changes in markers of inflammation from prior to study drug 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.Correlation between change in the inflammatory markers and the change in HB from prior to study drug to 6 months.