Coordinating Center Studies

Age Gene/Environment Susceptibility-Reykjavik-Bone Marrow Adiposity Study

This study is an ongoing population-based study of older men and women in Iceland. It was initiated to examine genetic susceptibility and gene/environment interaction as these contribute to phenotypes common in old age. AGES-Bone Marrow Adiposity Study is sponsored by NIAMS to determine the correlation of marrow adiposity with bone markers and other body composition parameters, such as bone density, body fat mass, visceral and subcutaneous adipose tissue, and fatty muscle infiltration.

Principal Investigator: Ann V. Schwartz, PhD, MPH
Project Director: Trisha F. Hue, PhD, MPH
Research Area: Bone, Adiposity
Status:
Ongoing

AFF

Atypical Femoral Fractures: A Population-Based Study of Risk Factors and Relationship to Bisphosphonate Exposure and Discontinuation)(AFF)

Dr. Doug Bauer, a UCSF General Internist and SFCC member for over 25 years, recently received an NIH grant to study the long-term effects of bisphosphonates, particularly the occurrence of atypical femoral fractures (AFF) which appear to be more common after prolonged bisphosphonate use. Along with UCSF Biostatistician Dennis Black and a Danish collaborator, he plans to analyse longitudinal pharmacy and fracture data from Denmark dating back to 1995. Dr. Bauer hopes to determine how the duration of bisphosphonate use and other risk factors, and discontinuation of bisphosphonates, relates to the risk of AFF in the Danish population.

Principal Investigator: Douglas C. Bauer, MD
Research Area: Bone
Status: Ongoing

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CALERIE

Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy

This study is a multi-center, parallel-group, randomized, controlled trial that's overall aim is to test the hypothesis that two years of sustained caloric restriction will slow aging and protect against age-related disease processes. UCSF is providing DXA Quality Assurance. BMD at the hip, spine and wrist, as well as composition of the total body are measured for the study, and UCSF is centrally analyzing and archiving all scans.

Principal Investigator: Ann V. Schwartz, PhD, MPH
Research Area: Aging/Longevity, Bone
Status: Completed

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CARGO

Comprehensive Evaluation of Aging-Related Clinical Outcomes and Geroproteins(CARGO)

Our study harnesses the comprehensive data and statistical power of the Cardiovascular Health Study (CHS) and Dynamics of Health and Body Composition Study (Health ABC) to analyze whether proteins discovered to delay or accelerate aging in the brain, heart, and skeletal muscle are associated with important clinical outcomes: dementia, heart failure, and mobility disability. Data and specimens from the Baltimore Longitudinal Study of Aging (BLSA) will enable us to understand how these proteins vary with age and influence the brain,heart and muscle across the life span. This study will provide a comprehensive picture of the potential of these proteins to give rise to new treatments for major causes of aging-related disability and mortality.

Principal Investigator: Steven R.Cummings, MD
Project Director: Robin Collins, MPH
Research Area: Aging/Longevity
Status: Ongoing

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Creatine Dilution

Determination of Skeletal Muscle Mass by Creatine Dilution

A novel measure of total body skeletal muscle mass is the creatine dilution method. Briefly, the total creatine pool size, and thus total body skeletal muscle mass, can be estimated by orally dosing individuals with deuterated creatine (d3-creatine) and then subsequently measuring labeled creatinine (d3-creatinine) in a single urine sample. We posit that total body skeletal muscle mass as measured by this method is related to strength and physical performance, and that individuals with decreased total body skeletal muscle mass will have an increased risk of falls, fractures and functional impairments. We use traditional methods such as receiver-operator curves, and newer approaches including the net reclassification index and predictiveness curves, to investigate whether total body skeletal muscle mass as determined by the creatine dilution method is superior to appendicular lean mass (from DXA), age, BMI and strength in predicting the risk of falls, fractures, mortality and mobility limitationin older men. We plan to efficiently test these hypotheses via an ancillary study to the ongoing Osteoporotic Fractures in Men (MrOS) study - a large, well-characterized, prospective, multicenter study. We propose to add this measure to the already funded study Visit 4. Should our hypotheses prove correct, the creatine dilution method for assessing total body skeletal muscle mass would become a critical research tool used to elucidate the pathophysiology of sarcopenia. By providing a highly precise method to monitor response, the creatine dilution method will aid the development of novel agents for reversing age-related muscle loss. This simple test could be used clinically as an alternative to DXA to identify men at risk of physical decline and to refine sarcopenia definitions.

Principal Investigator: Peggy Cawthon, PhD
Research Area: Aging Muscle 
Status: Ongoing

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D3-creatine

Evaluating D3-creatine dilution estimates of muscle mass due to weight loss and exercise in older adults who have obesity

This study will evaluate the impact of weight loss resulting from caloric restriction (with or without exercise) on muscle mass in older adults with obesity. Muscle mass will be measured with the new D3Cr dilution method. We will also determine whether the change in muscle mass is related to the change in physical performance that accompanies weight change.

Principal Investigator: Peggy Cawthon, PhD
Research Area: Aging Muscle 
Status: Pending

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FLEX

FIT Long-Term Extension

This study assesses the effects of continuing alendronate beyond 5 years. Postmenopausal women (N=1,099) who had previously been randomized to alendronate in FIT (Fracture Intervention Trial) were randomized to 5 years of continued alendronate.

Principal Investigator: Dennis M. Black, PhD
Research Area: Osteoporosis
Status: Completed

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FREEDOM

Fracture Reduction and Evaluation of Denosumab in Osteoporosis every 6 Months

In this phase III trial, the Coordinating Center was responsible for adjudication of cardiovascular events and deaths and leadership and management of the Steering and Publication Committees. The trial involved over 7,000 participants at 350 sites.

Principal Investigator: Steven R. Cummings, MD
Project Director: Dana Kriesel, MPH
Research Area: Bone, Osteoporosis
Status: Completed

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HABC

Health, Aging, and Body Composition Study

This observational study looks at the onset of physical disability in relation to body composition change, particularly loss of muscle mass in old age. The study began in 1996, has two sites, and over 3,000 participants.

Principal Investigators: Steven R. Cummings, MD, Michael C. Nevitt, PhD, MPH
Project Director: Susan M. Rubin, MPH
Research Area: Aging/Longevity, Muscle
Status: Ongoing

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HORIZON-PFT/Extension

Health Outcomes & Reduced Incidence with Zoledronic Acid Trial

The initial study was a phase III, 3-year international, multi-center, randomized control trial of over 7,000 postmenopausal women in 27 countries for the treatment of osteoporosis and other health outcomes with yearly zolendronic acid versus placebo. Extension 1 is a 3-year extension to look at outcomes such as fracture, bone mineral density, and other adverse events after 6 years. Extension 2 is a 3-year extension of Extension 2 and includes continued treatment and monitoring of outcomes after 9 years.

Principal Investigator: Dennis M. Black, PhD
Project Director: Trisha F. Hue, PhD, MPH
Research Area: Bone, Osteoporosis
Status: Completed

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Longevity Consortium

The Coordinating Center has been a leading participant of this consortium of scientists interested in the genetics of aging and age-related traits. The consortium is funded by a 3-year grant from the National Institute on Aging.

Principal Investigators: Steven R. Cummings, MD, Gregory J. Tranah, PhD
Project Director: Dan Evans
Research Area: Aging/Longevity
Status: Ended

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Longevity Genomics

Integrative Resource to Develop Translational Strategies to Promote Longevity

Translation of genetic associations into insights that can lead to pharmacological interventions designed to promote healthy aging requires an approach and infrastructure that integrates many sources of information and scientific expertise. We propose the creation of an infrastructure and an integrated data system to enable our team of scientists to develop therapeutic research strategies based on causal connections between molecular traits and healthy aging, and chemicals that target the molecular traits. Therapeutics that can promote healthy aging can have a great impact on the elderly, a rapidly growing subgroup of our population

Principal Investigator: Steven R. Cummings, MD
Project Director: Dan Evans, PhD
Research Area: Aging/Longevity, Genetics
Status: Ongoing Website: http://www.longevitygenomics.org

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Look AHEAD

Action for Health in Diabetes

This study is a randomized controlled clinical trial that is designed to characterize the impact on several health outcomes of an intervention program designed to produce weight loss. The primary study objective is to determine whether such a program is effective in reducing the number of serious cardiovascular disease events in a cohort of overweight adults with type 2 diabetes. The Coordinating Center serves as the bone density quality assurance group for the study. Hip, spine, and whole body scans are sent to us for quality and technical review and central databasing.

Principal Investigator: Michael C. Nevitt, PhD, MPH
Project Director: Ann V. Schwartz, PhD, MPH
Research Area: Cardiovascular, Diabetes
Status: Ongoing

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MOST

Multi-center longitudinal, prospective observational cohort study of knee osteoporosis

This study looks at risk factors for the development and progression of knee osteoarthritis and knee pain. A cohort of more than 3,000 women and men, aged 50 and over are participating in follow-up visits to help investigators better understand how to prevent and treat knee osteoarthritis, one of the most common causes of disability in adults.

Principal Investigator: Michael C. Nevitt, PhD, MPH
Project Director: Jean Hietpas, MSW, OTR
Research Area: Osteoarthritis
Status: Ongoing Website: http://most.ucsf.edu

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MrOS

Osteoporotic Fractures in Men

This prospective cohort study is designed to examine the extent to which fracture risk is related to bone mass, bone geometry, lifestyle, anthropometric and neuromuscular measures, and fall propensity, as well as to determine how fractures affect quality of life in older men. A total of 5,995 from six US clinical centers were enrolled between March 2000 and April 2002. Participants have been followed since enrollment for incident fractures, falls, prostate cancers, and death. The MrOS study is funded by NIA and NIAMS, currently through June 2012.

Principal Investigators: Douglas C. Bauer, MD, Steven R. Cummings, MD
Project Director: Robin M. Fullman, MPH
Research Area: Bone, Osteoporosis
Status: Ongoing
Website: http://mrosdata.sfcc-cpmc.net

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MrOS Sleep

Outcomes of Sleep Disorders in Older Men

This study is an ancillary study to the MrOS study. From December 2003 through March 2005, 3,135 MrOS participants were enrolled. Comprehensive and objective assessments of sleep (including overnight in-home polysomnography[PSG], 5-day wrist actigraphy and self-reported measures of sleep quality), adjudication of incident cardiovascular (CVD) events, and other measures including neuromuscular function, bone mineral density, and cognitive function were added to the expansive dataset of the MrOS study. The MrOS Sleep Study is funded by NHLBI. Current funding is through April 2014.

Principal Investigator: Katie L. Stone, PhD
Project Director: Robin M. Fullman, MPH
Research Area: Aging/Longevity, Cardiovascular, Sleep
Status: Completed
Website: http://mrosdata.sfcc-cpmc.net

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OAI

Osteoarthritis Initiative

This study is a scientific evaluation of biomarkers for osteoarthritis as potential surrogate endpoints for disease onset and progression.

Principal Investigator: Michael C. Nevitt, PhD, MPH
Project Director: Susan M. Rubin, MPH
Research Area: Osteoarthritis
Status: Ongoing Website: http://oai.ucsf.edu

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PaTH/PaTH II

PTH and Alendronate in Combination for the Treatment of Osteoporosis

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Follow-up of PTH and Alendronate in Combination for the Treatment of Osteoporosis PaTH was a 2-year randomized controlled trial of 238 participants at 4 clinical sites to determine if 3 different combination treatments of PTH 1-84 with alendronate increased bone mineral density and bone turnover markers more than alendronate alone. PaTH II was a 1-year observational study designed for a 3rd year of follow-up in women originally randomized into PaTH to assess if MBD continues to increase or is maintained in those treated with PTH followed by a bisphophonate.

Principal Investigator: Dennis M. Black, PhD
Project Director: Trisha F. Hue, PhD, MPH
Research Area: Bone, Osteoporosis Status: Completed

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PICS

PTH and Ipandronate Combination Study

This is a randomized, placebo-controlled trial in which two combinations of PTH and oral ibandronate (Boniva®) are used to determine the effect on bone markers and bone mass. Forty-four post-menopausal women aged 55+ with low bone density as measured by densitometry were enrolled in this single-center pilot study. Participants will have 24 months of follow-up for clinical exams, imaging, and biomarker measurements. The study includes novel imaging methods including high resolution peripheral CT and MRI X-ray spectroscopy.

Principal Investigator: Dennis M. Black, PhD
Project Director: Jean Hietpas, MSW, OTR
Research Area: Bone, Osteoporosis Status: Completed

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ROSTERS

Randomized Order Safety Trial Evaluating Resident Schedules

Dr. Katie Stone is serving as the PI of the Data Coordinating Center (DCC) for the ROSTERS Trial (Randomized Order Safety Trial Evaluating Resident Schedules). ROSTERS is a multi-center randomized crossover trial in six pediatric ICUs staffed by PGY2 and PGY3 residents to compare the effectiveness and safety of a sleep and circadian science-based (SCS) intervention schedule with a traditional schedule that includes frequent shifts of 24 hours or longer. The primary outcome is resident-related preventable adverse events and near misses, and the secondary outcomes are ICU-wide preventable adverse events and near misses and resident neurobehavioral performance and predicted driving safety. The study aims to enroll 300 residents over the course of three years. The first wave of two sites began data collection on November 1, 2013.

Principal Investigator: Katie L. Stone, PhD
Project Director: Dana Kriesel, MPH
Research Area: Aging/Longevity, Cognitive function, Sleep
Status: Ongoing

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Sleep Cog

Changes in Sleep and Cognition in Older Women

This study is designed to look at the relationship between poor sleep quality and cognitive function and mortality. The study will also explore potential biochemical pathways that may mediate the inter-relationships between sleep conditions, cognition, and mortality.

Principal Investigator: Katie L. Stone, PhD
Project Director: Dana Kriesel, MPH
Research Area: Aging/Longevity, Cognitive function, Sleep
Status: Ongoing

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SOF

Studies of Osteoporotic Fractures

At the onset of this study 20 years ago, the main specific aims were to determine risk factors for hip and other osteoporotic fractures. Since then, the aims have expanded to include additional diseases and conditions common in older women, including breast cancer, osteoarthritis, stroke, cognition, vision, and sleep.

Principal Investigator: Steven R. Cummings, MD
Project Director: Dana Kriesel, MPH
Research Area: Bone, Osteoporosis
Status: Ended Website: http://sof.ucsf.edu

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SOMMA

The Study of Muscle Mobility and Aging

In the Study of Muscle Mobility and Aging (SOMMA), a prospective, longitudinal study of men and women age 70 to 90, our team of experts in clinical and laboratory sciences will use innovative and state-of-the-art technologies with rigorous quality control to test these hypotheses and discover new pathways for the loss of mobility with aging. We will measure quadriceps contractile volume by MRI and total muscle mass by d3 creatine dilution. We will use 31PMRS to assess the capacity of the quadriceps to generate ATP (ATPmax). In tissue form muscle biopsies quantify denervation and oxidative damage to contractile proteins. SOMMA will be the first to quantify autophagic flux to assess the role of autophagy in the loss of mobility with aging. We use respirometry on fresh tissue to quantify the contribution of mitochondria to ATPmax and mobility disability. These properties interact: for example, decreased autophagic flux promotes the accumulation of oxidative damage and denervation, and understanding these relationships will guide the analysis and interpretation of our results.  Furthermore, we will use unbiased RNA-sequencing (RNA-seq) to profile the entire transcriptome to discover new associations between clusters of genes and individual variation in rates of loss of fitness (peak VO2), muscle mass, and risk of mobility disability.

SOMMA may identify and prioritize targets for new therapeutics and tailored exercise regimens. We also will create a unique archive of tissue, blood, with longitudinal data about important clinical outcomes that the scientific community can use to efficiently test new hypotheses about muscle and loss of mobility with aging.

Principal Investigator: Steven R. Cummings, MD
Project Director: Robin Collins, MPH
Research Area: Aging Muscle, mobility
Status: Ongoing

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STRIVE

The STRIVE Study: Breast Cancer Screening Cohort for the Development of Assays for Early Cancer Detection

Detection of early stage cancer may be possible through analysis of circulating cell-free nucleic acids (cfNAs) shed into the blood by tumors. Using high-intensity sequencing (based on broad genomic coverage and deep sequencing) of cfNAs, combined with machine learning, to develop blood tests to detect cancer early. The purpose of this prospective, multi-center, observational cohort study is to train and validate an assay for the early detection of breast cancer. The study will collect blood samples from participants within 28 days of their screening mammogram. Additional blood samples will also be collected for a subset of participants. For participants who receive a cancer diagnosis during the study, tissue samples will be collected.

Principal Investigator: Steven R. Cummings, MD
Project Director: Dana Kriesel, MPH
Research Area: Breast Cancer
Status: Ongoing Website: http://www.joinstrive.com/

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TOLSURF

Trial of Late Surfactant in Premature Babies

This study is a randomized, multi-center, placebo-controlled trial of late surfactant treatment in infants at high risk of bronchopulmonary dysplasia (BPD). The primary aim of this nationwide trial, funded by NHBLI, is to assess the effect of late doses of surfactant on the occurrence and severity of BPD in ventilated, extremely low gestational age newborns (ELGAN) receiving inhaled nitric oxide (iNO). A cohort of 524 infants will be enrolled and followed for up to 24 months to help investigators better understand whether surfactant will decrease risk of chronic lung disease and improve pulmonary outcome in the ELGAN population. See also TOLSURF-Pilot.

Principal Investigator, Clinical Coordinating Center: Roberta Ballard, MD
Principal Investigator, Data Coordination Center: Dennis M. Black, PhD
Project Director: Jean Hietpas, MSW, OTR
Research Area: Neonatology Status: Completed

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VEST-PREDICTS

Vest prevention of Early Sudden death Trial (VEST); PREDiction of ICD Therapies Study (PREVENTS)

This study is a multi-center randomized controlled trial and observational follow-up study designed with the goal of improving clinical care for persons at risk of sudden death from heart arrhythmias. Participants include men and women aged 18 years and older with some heart dysfunction after a recent heart attack. The goal of VEST is to determine whether use of a wearable defibrillator vest reduces death in the first 2 months following the heart attack. In PREDICTS, extensive risk stratification testing will be performed and biological samples collected from each study participant with the goal of predicting which persons truly require implantation of a cardioverter-defibrillator device (ICD).

Principal Investigators: Stephen B. Hulley, MD, MPH, Mark J. Pletcher, MD, MPH
Project Director: Trisha F. Hue, PhD, MPH
Research Area: Cardiovascular Status: Ongoing

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Zolpidem and Cognitive Behavioral Therapy for Insomnia in Older Adults

Planning funding is provided for the development of a large multi-center randomized trial designed to test the comparative effectiveness of zolpidem versus cognitive behavioral therapy for insomnia in older adults. The trial will be powered to test key outcomes in older adults such as falls, cognitive and physical function, and cardiovascular risk factors.

Principal Investigator: Katie L. Stone, PhD
Project Director: Dana Kriesel, MPH
Research Area: Aging/Longevity, Sleep, Cognitive function Status: Completed

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