Date: October 29, 2013
For many years, Naresh Punjabi has sought to determine whether sleep apnea causes metabolic abnormalities that can lead to type 2 diabetes and heart disease. New understanding of how these chronic illnesses develop in people with sleep apnea, he says, could improve the lives of millions.
Now the Johns Hopkins pulmonologist and sleep researcher is closing in on the answer with significant help from the Johns Hopkins Institute for Clinical and Translational Research (ICTR), a center established to speed up and improve the process of getting promising research from the lab into the clinic and eventually to the community. Punjabi says the ICTR has provided resources that dramatically lowered the cost of his study and eliminated many logistical hurdles.
Because of the ICTR, he has access to specially designed sleep rooms, monitoring equipment, nurses and nutritionists. These resources allow him to measure metabolic function in more than 100 healthy participants—both obese and of normal weight—who have sleep apnea, a sleep disorder characterized by pauses in breathing.
Punjabi’s study is one of 346 currently supported by the ICTR, which was created in 2007 with a $100 million grant from the National Institutes of Health. About 60 such centers now exist nationwide, instructed by NIH to “accelerate discoveries toward better health” and to collaborate with each other when possible, says institute director Daniel Ford, the school of medicine’s vice dean for clinical investigation. The ICTR also exemplifies Johns Hopkins Medicine’s strategic priority to advance biomedical discovery by using resources across the enterprise to expedite scientific collaborations.
Research supported by the ICTR ranges from a study of bladder stone risk for people with spina bifida to an analysis of food availability and nutrition in low-income neighborhoods, and includes investigations of HIV, asthma, allergies and kidney disease.
With clinical research units in The Johns Hopkins Hospital, Johns Hopkins Bayview Medical Center and Kennedy Krieger, the ICTR maintains a low profile, but its impact is enormous, says deputy director Charles Flexner, who oversees research taking place in the ICTR’s clinical research units. “The goal is to make clinical research easier,” he says. “We recognize there are already so many hurdles an investigator has to jump through for research involving human subjects.”
Punjabi, for example, conducts his research in the Institute’s Center for Interdisciplinary Sleep Research and Education in the 301 Building on the campus of Johns Hopkins Bayview Medical Center. With a multiyear grant of $1.6 million from the National Institutes of Health, he is working to untangle cause-and-effect relationships between obesity, sleep apnea and such metabolic abnormalities as diabetes.
In the study, participants age 21 to 75 spend one night in a room equipped with infrared cameras and other monitoring equipment. While they sleep, machines collect detailed data about their brain activity, eye movement, breathing, heart rate and body motion. Then, for the next two months while they sleep at home, subjects avert their apnea with a mask that provides CPAP—continuous positive airway pressure.
Finally, they return for an overnight stay, and follow-up measurements, in the Bayview sleep lab. The results will give Punjabi a clearer picture of the role sleep apnea may play in metabolic irregularities.
The ICTR sleep research center, says Punjabi, “provides a venue for shared resources for technically challenging research.” Used by about 15 sleep researchers at Johns Hopkins, it has eight sleep rooms, including several that feature small throughways that allow technicians to take blood samples without waking the subject. Other resources include highly skilled nurses, on-site nutritionists, an exercise room with a treadmill for stress tests, a DEXA scanner to measure body fat and bone density, and a control center for collecting and analyzing data.
Managing Multiple Collaborations
The ICTR, which replaced the General Clinical Research Centers, supports faculty research throughout the university, including the schools of medicine, engineering, nursing and public health. Its staff of roughly 60 includes research program managers, budget specialists, staff members who run training and education programs, nurses and nutritionists, says Gerry Stacy, ICTR administrative manager. Research navigators—“people who know how research works at Hopkins”—are available to work with investigators to help them develop and refine their ideas. First-timers, in particular, benefit from guidance on how to design clinical trials and leverage ICTR resources.
Also within the ICTR is the Clinical Research Network, established in 2009, which creates clinical research collaborations between Johns Hopkins and community hospitals, including the Greater Baltimore Medical Center, Anne Arundel Medical Center, Inova Health System in Northern Virginia, Peninsula Regional Medical Center on Maryland’s Eastern Shore, and Reading Hospital in Pennsylvania.
The Value of ICTR Support
Kathryn Wagner, an associate professor of neurology and neuroscience at the school of medicine, is conducting research that could slow the progression of Duchenne muscular dystrophy (DMD), which afflicts one in 5,000 boys worldwide. As it progresses, the condition robs them of their ability to walk, to breathe normally and, finally, to live past early adulthood.
In June, she and research partner Stanley Froehner of the University of Washington won a three-year, $7.3 million grant to develop a novel drug for DMD. The project will culminate in a randomized, placebo-controlled phase 2 trial in boys age 7 to 13 who have DMD.
Wagner also directs the Center for Genetic Muscle Disorders at the Kennedy Krieger Institute. She believes she won the grant from the National Center for Advancing Translational Sciences (NCATS) in part because of support from the ICTR, which is providing space in the pediatric clinical trials unit as well as consultations with a biostatistician. Earlier, she won a pilot grant from the ICTR’s Accelerated Translational Incubator Program (ATIP). She also credits the ICTR’s Science of Clinical Investigation series with helping her learn, early in her career, how to plan an ethical and effective clinical trial and to analyze the data.
“I’ve actually been really impressed over the years with how much I’ve used ICTR,” she says. “I’m a frequent flyer.”
In late September, the ICTR learned that it would receive a second five-year NIH grant, this one for $72 million. The funding trim of about 20 percent “isn’t going to change our mission,” Stacy says, though it may mean finding more ways to share costs with investigators.
The ICTR is expected to establish three Translational Research Communities that will focus on developing drugs and vaccines; biomarkers and diagnostic tests; and devising interventions to help change behaviors like smoking through collaborations across departments.
Also new will be the ICTR Research Studio, which will allow investigators to meet with many experts at one time to share ideas and discuss clinical trial logistics in half-hour or hour-long sessions. Stacy says the changes respond to the NIH’s call to make translational science more collaborative, effective and efficient. “This is our way of saying, ‘This is how we can do it at Hopkins.’”
A Sampling of Studies
The ICTR currently supports 346 studies, a number that’s “way higher than it’s been in the past,” says Administrative Manager Gerry Stacy. The studies at right show the range of research.
Monitoring Recovery from an Episode of Severe Mental Illness
A Prospective Cohort Study of Immune Mechanisms, Genetic Factors, Clinical and Environmental Characteristics Associated with the Occurrence and Clinical Outcome of Peanut Allergy
Oral Glucose Tolerance Test for Alzheimer’s Disease Biomarker Development
Development of a Pediatric Asthma Control and Communication Instrument
The Improving Patient Outcomes with Respect and Trust (IMPORT) Study
Whole Blood Assay for Testing New Drug Combinations against Tuberculosis
A Randomized Study of Human-Milk-Based versus Bovine-Based Nutrition for Very
Low Birth Weight Preterm Infants
Potassium Intake in Patients with Chronic Kidney Disease
SPACE AND SUPPORT: How the ICTR Helps Researchers
- Physical space: Investigators can use five clinical research units—an adult outpatient research clinic and an adult inpatient research unit at The Johns Hopkins Hospital, a combined pediatric inpatient and outpatient unit at JHH, a combined adult inpatient and outpatient unit at Bayview, and a clinical research unit at Kennedy Krieger for developmentally disabled trial participants.
- Education: A predoctoral training program accepts 10 medical students annually, who postpone their medical studies for a year to pursue training in clinical investigation. Another program for clinical research scholars provides two years of protected time for fellows and junior faculty pursuing an M.H.S. or Ph.D. in clinical investigation.
- Pilot grants: The ICTR has awarded 50 Accelerated Translational Incubator Program (ATIP) grants of up to $100,000 to fund researchers who need resources to move their discoveries more rapidly along the path to widespread clinical use.
- Experts: Help from biostatisticians, nutritionists and others.
Assistance recruiting and screening subjects, securing grants and ensuring that the research meets high standards of ethics and safety.