ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): study methodology, recruitment, and baseline demographic and disease characteristics

Abstract

Abstract In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods utilize an extensive structured telephone interview ascertaining environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3-6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Three hundred and fifty-five patients were recruited. Subjects were enrolled over a 36-month period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Results showed that demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, the only difference being type of health insurance among enrolled patients. Sites were divided into three groups by the number of enrolled subjects. Comparing these three groups, the Columbia site had fewer 'definite ALS' diagnoses. This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and has been accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized.

Keywords: ALS; disease progression; epidemiology; oxidative stress; survival.

Figure 1

This is a multicenter design consisting of 16 ALS clinic study sites. The distribution of sites is fairly evenly dispersed throughout the Unites States.

Figure 2

The overall enrollment performance is demonstrated. The anticipated target was 350 patients (broken line). The Columbia University Coordinating Center enrolled 67 live patients from an earlier study, who agreed to participate in this study, and also began recruiting patients before other sites. Actual enrollment (solid line) showed a clear slowdown in the middle of the enrollment period, to 4.5 patients per month. Although the ceftriaxone clinical trial continued their enrollment throughout most of the COSMOS study, other clinical trials enrolled in the middle of the COSMOS study, perhaps one of the reasons why enrollment slowed down. TL: talampanel, NP: NP9001, DX: dexpramipexole, CK: CK2017357

Figure 3

The Columbia site had two patient populations composed of C1, an earlier MDA study (67 patients), and C2, usual recruitment based on the current NIH ALS COSMOS study.

Figure 4

Mean age for males was 59.7 ± 10.8 years (median=60.3 years) and 63.2 ± 9.2 years (median=64.3 years) for females.