It's 9 a.m. in the Clinical and Translational Study Unit (CTSU) at Children's Hospital Boston. Ron McElman, the unit's administrative assistant, sits at the front desk taking phone calls and checking in arriving families. Down the hall, a child with autism hollers while nurses, aided by a Child Life Specialist, attempt to prepare him for a blood draw. In another room, laughter erupts as a team of technicians test a child's muscle strength. Across from Ron's desk, a worker hangs a picture; it was donated by the mother of a child receiving an experimental treatment for Hutchinson-Gilford progeria, a rare disorder that predisposes children to premature aging.
Patients come to this floor of the hospital's inpatient building not for check-ups or treatment, but to take part in clinical research. The unit, which also includes eight inpatient beds, houses more than 100 ongoing studies, from those investigating the presence and impact of allergens in inner-city schools to clinical trials testing new medications for early heart disease.
"Part of Children's mission is to take findings generated in its laboratories and translate them to the bedside, and the CTSU provides the space and resources to make that possible," says Catherine Gordon, MD, MSc, director of the Bone Health Program at Children's. Gordon uses the unit's Dexa bone scanner to monitor bone loss in patients with anorexia and deteremine whether hormone therapy can curb the loss. The CTSU's resources include not only specialized, high-end equipment, but statisticians, bioinformatics experts and clinical staff highly trained in gathering precise measurements.
"Nowhere else in the hospital has the same mission, where medical procedures are done only for research," says Ellis Neufeld, MD, PhD, associate chief of Children's Division of Hematology/Oncology. Neufeld, who studies genetic blood disorders, is the Site Implementation Director at Children's for Harvard Catalyst, the NIH-funded, Harvard-wide program of which the CTSU is part. "If the clinical studies were diluted all over the hospital, we would lose that core expertise that is so critical to running a successful trial."
Some studies in the unit, which is directed by Richard Grand, MD, hold promise for developing better care, treatment or even a cure. Others simply help doctors and scientists understand the disease better.
"Lots of trials say right in the consent form that the study won't help their own child," McElman says. "But the parents hope that other kids with this condition will benefit."
Healthy children, who serve as controls for the studies, also come to the unit—and are often the most difficult to recruit since their families' motives are mainly altruistic. For both patients and controls, modest incentives such as gift certificates are offered to compensate for their trouble.
Eleven-year-old Brett Nasuti reclines, smiling, in La-Z-Boy, wearing a "Got Milk?" t-shirt. It's 10 a.m., and he's just consumed one and a half ounces of milk, an impressive feat for a boy with a life-threatening milk allergy. "When I was little, I got hives in the shape of my mom's lips when she kissed me after drinking coffee with just a little milk in it," he says.
Brett is in the final months of a milk desensitization trial. Doctors have found that general seasonal allergy shots also suppress the body's reaction to other allergens, like peanuts and milk. Children's allergist and immunologist Dale Umetsu, MD, PhD, the trial's principal investigator, hopes this suppression will provide a window allowing milk to be introduced slowly into the patient's diet, so resistance can build up over time.
Brett’s already had his allergy shot, and now, after his milk dose, nurses will closely monitor his vital signs for the next two hours, ready with IV medications to combat any reaction. But Brett’s confident he won’t need the drugs and that the trial will work. "I’m looking forward to eating ice cream with my friends," he says. "And I’m having a pizza party when this is all done."
It's now noon and two project coordinators stand tense and huddled at the front desk. One taps her nails; the other fiddles with a file. Their research subjects, a family coming in for an autism study, are running late. The study, led by Louis Kunkel, PhD, director of Children's Program in Genomics, is examining family history and neurological and physical development in children with autism. The exam includes a photogrammetry camera that takes 3D images of the face, which might give clues to an underlying genetic syndrome. Each family member must also have blood drawn so researchers can analyze their DNA.
And that's the problem. The family has phoned McElman at the front desk twice to let him know they're late because one of the patient's siblings is balking at the blood draw. The coordinators ask McElman to track down Brianna Matney, the unit's Child Life Specialist. She has a bag of tricks to ease children's anxiety about medical procedures—a lifelike baby doll with fake blood that kids can draw with a real syringe, a fake arm that kids can insert IV tubing into and M&Ms to help kids cope with taking pills. "Letting kids have control over the item that is usually beyond their control is amazingly empowering for them," Matney says. "It really changes their perspective on the situation."
But the coordinators didn't end up needing Matney that day because the family never made it to the CTSU.
"Families enroll with the best of intentions, but often find it hard to actually come for their appointments," says Kristine Jordan, the CTSU's administrative director. "Unlike medical appointments, they don't really need to come to a research appointment, and there's the temptation to cancel when other things come up."
Konstantin and Petra Mijanovic arrive on the CTSU at 1 p.m. The teenagers are among 400 people in the world who lack a critical blood-clotting enzyme called Factor XIII, leaving them vulnerable to internal bleeding. They're here as part of the first clinical trial of a synthetic Factor XIII.
Since infancy, they have been bound by monthly hospital visits to get intravenous infusions of Factor XIII. But the trial, led by Neufeld, offered them the chance to take recombinant Factor XIII in shot form—a treatment they could potentially administer themselves at home. "I was really excited to just have to take a shot once a month," says 15-year-old Konstantin. "I would have been able to explore the world if I wanted to... the promise was a lot of freedom."
To their great disappointment, both Konstantin and his sister developed antibodies to the shot after their first treatment and had to withdraw from the 40-patient trial. Today they're here to resume their monthly infusions and provide blood samples for monitoring the recombinant antibodies, so Neufeld can better understand their unusual immune reaction.
"Whenever you're part of a medical study, there are risks," Konstantin says. "But you are also at the frontiers of medicine. It's a step forward in the right direction."
It's 2 p.m. and each room in the CTSU is full as nurses, project coordinators and doctors dash around. In one room, an adolescent boy is having his blood sugar measured, paying his final visit in a six-month-long nutritional diet study led by Sarah De Ferranti, MD, MPH, director of Children's Preventive Cardiology Clinic. The goal has been to bring down his weight and blood pressure through sustainable lifestyle changes instead of medication. For the first two months of the trial, dieticians provided him with meals six days a week, including a family meal once a week, prepared in the unit's kitchen. In his case, the intervention has so far been a success.
Down the hall, a 7-year-old girl who suffers from short bowel syndrome (loss of a large part of her intestine) is having her metabolism tested, wearing what she calls an "astronaut helmet" on her head. This device, an indirect calorimeter, measures energy expenditure by analyzing her exhaled breath, as part of a study led by Nilesh Mehta, MD, in the Pediatric Critical Care Nutrition Program.
Meanwhile, Jordan meets with a doctor who is preparing to start his own trial, and escorts him on a tour of the unit. The CTSU is especially valuable to early-career physician-scientists, helping to supplement their meager funding and resources, and in pilot studies, which don't yet have the data behind them to obtain sufficient grants.
Last year Jordan extended the CTSU's reach by initiating an off-unit clinical research group that brings the unit's staff, resources and expertise to other regions of the hospital, such as the Emergency Department and the Newborn Intensive Care Unit, and to collaborating institutions. This afternoon, Mark Berry, clinical research coordinator, is bringing urine samples from Children's Cardiac Intensive Care Unit to the Harvard Institute of Medicine across the street, where Michael Ferguson, MD, in the Division of Nephrology, is using them to study acute kidney injuries. The unit can also send staff to schools and patients' homes.
It's late afternoon and the day is finally winding down. Today 10 patients were on the schedule, three showed up late, one showed up early and two didn't show up at all. Relying largely on a Palm Pilot, McElman has spent much of the day rescheduling and reshuffling rooms and equipment.
Brett, done with his allergy monitoring, is the first to depart, carrying a cooler full of small servings of milk for him to consume each day until he returns for his dose increase next week. As he walks by the front desk, McElman teasingly asks if he can keep Brett's milk. "No way!" Brett says, laughing.
Given the diversity and quantity of studies going on, there's no typical day in the CTSU, and no amount of planning can guarantee each day will go smoothly. Jordan, who's been here since 7 a.m., will stay until late in the evening, working on grant applications to ensure the unit will have the facilities, supplies and staff needed to run clinical trials, and to help implement future studies, such as a gene therapy protocol for a form of severe immunodeficiency (see a sampling of studies in the pipeline).
Other departments in the hospital continuously pressure Jordan to let them utilize the CTSU's space and facilities for clinical appointments and meetings. "There's always a high demand for space in the hospital, and we try to accommodate everyone, but it's absolutely critical that we maintain protected space, time and resources for research," says Jordan. "Only then can we continue to innovate and provide our patients with the most effective care available.