STATEMENT-OF-WORK-AREDS2 - SAM.pdf

Statement of Work (SOW)

Office of Acquisitions.

Metabolomics Evaluation of the Age- Related Eye Disease Study 2 (AREDS2)

Statement of Work

TABLE OF CONTENTS

1.0 Introduction 2

1.1 Background 2

1.2 Scope 2

1.3 Objectives 2

2.0 Requirements 3

2.1 Tasks 3

2.2 Deliverables 3

2.3 Schedule 4

2.4 Assumptions 4

3.0 Government Furnished Property 4

4.0 Security Requirements 4

1.0 INTRODUCTION/OVERVIEW

The purpose of this study is to evaluate metabolites using non-targeted metabolomics platforms in the serum of 556 participants (with 2001 blood tubes) of men and women aged 55 and older who are enrolled in the randomized controlled clinical trial, the Age- Related Eye Disease Study 2 [AREDS2] 2006-2012) of oral supplements for treatment of age-related macular degeneration (AMD).

1.1 BACKGROUND

Age-related macular degeneration (AMD), a chronic neurodegenerative disease, is the leading cause of blindness in the United States and developing countries. The pathogenesis of AMD is not known. Researchers have focused on the genetics of AMD to provide information regarding the potential pathways involved in the mechanisms of disease. More recently, a few studies involving smaller sample sizes have evaluated the metabolomics of patients with AMD compared with controls in cross-sectional studies.

These studies help us understand the potential pathogenesis of AMD. This can lead to new targets for the treatment of AMD.

In 2001, the Age-Related Eye Disease Study demonstrated that a combination of antioxidant vitamins that included vitamins C, E, beta-carotene and zinc and copper reduced the risk of progression to vision-threatening late forms of AMD. A subsequent study, AREDS2 (2006 to 2012) enrolled persons aged 55 or older for a clinical trial that evaluated the role of adding lutein and zeaxanthin and/or omega 3 polyunsaturated fatty acids to the original AREDS supplements. Blood was collected in AREDS2 at baseline and every 2 years throughout the duration of the clinical trial. In this proposal, we have an opportunity to evaluate metabolomics of participants who were enrolled in a large clinical trial of oral supplements for the treatment of AMD and the advantage is that we can review the metabolites in a longitudinal study, providing repeated measures of the blood.

1.2 SCOPE

We will evaluate metabolites in a non-targeted manner on baseline and follow-up serum samples of AREDS2 participants. We have 556 AREDS2 participants who were followed over 5 years with 2001 AREDS serum samples available in total. The potential goals include identifying metabolites associated with and mediate AMD risk for a number of

1.3 OBJECTIVES

We will evaluate the baseline metabolites in a non-targeted manner and compare the metabolomic results between placebo and treatment. We have 556 AREDS2 participants who were followed over 5 years with 2001 AREDS serum samples available in total. We will also assess the differences in the metabolites in those who progressed vs. those who did not progressed to vision-threatening late AMD. In addition, we have whole genome sequencing on this cohort and will evaluate the relationship of the specific genes and genetic risk score with the metabolites, specifically pathways will be examined. The potential goals include identifying metabolites associated with and mediate AMD risk for the following sets of highly-influential SNPs: (1) in complement genes (CFH, C3, C2/CFB, CFI, C9), (2) in lipid metabolism genes (ABCA1, CETP, APOE, and LIPC), and

(3) in HTRA1/ARMS2. These identified metabolites can be useful as biomarkers, which in combination with genotypic information, can predict AMD status and prognose progression risk with high accuracy. Other pathways may include oxidative stress, mitochondrial dysfunction, etc

2.0 REQUIREMENTS

2.1 TASKS

This section defines the tasks that the contractor must complete during contract performance.

STUDY START UP (INITIATION PHASE)

1. The budget does not include an in-person or investigator meeting.

2. Provide a dedicated project manager and a backup project manager to coordinate startup activities and maintain study timelines.

3. Develop a plan to document study roles, responsibilities, workflow and evaluation questions

4. Contractor will build a relative concentration profile of all structurally named small-molecule entities (>1,000), which can include both endogenous compounds, xenobiotics, and their metabolites, extracted from the samples and detected using its integrated metabolomics platform.

5. Contractor will build a relative quantitation for reproducibly measured unnamed compounds with contractor specific identifiers.

STUDY MAINTENANCE (ONGOING PHASE)

1. Check-in and review of all sample submissions, which includes:

• Sufficient quantity (>150 uL) of serum/plasma in the cryotubes.

2. Conduct the measurements of the non-target metabolites within 4-5 months.

• Contractor will build a relative concentration profile of all structurally named small-molecule entities (>1,000), which can include both endogenous compounds, xenobiotics, and their metabolites, extracted from the samples and detected using its integrated metabolomics platform.

STUDY CLOSEOUT (COMPLETION PHASE)

1. Provide final data export as an excel spreadsheet to NEI/NIH and NCATS

2.2 DELIVERABLES

The data from the evaluation of the metabolites will be exported at the end of the study to NEI/NIH and

NCATS.

2.3 SCHEDULE

All changes to the scope will be submitted in writing to contractor.

12 months from award date.

2.4 ASSUMPTIONS

NEI owns the data rights for the study protocol, experimental record and the final study report.

3.0 GOVERNMENT FURNISHED PROPERTY

N/A

4.0 SECURITY REQUIREMENTS

N/A