Groundbreaking MOBILITY Study Enrolling 1st Volunteers

The announcement in April 2015 of a $12.9 million contract award to assess strategies for minimizing obesity and weight gain in children with bipolar disorders made a big splash on the UC medical campus and beyond. Now, eight months later, researchers have laid the groundwork and are enrolling the first volunteers in what is expected to be a groundbreaking clinical study.

The study, titled "MOBILITY: Metformin for Overweight and Obese Children and Adolescents with Bipolar Spectrum Disorders Treated with Second-Generation Antipsychotics,” was approved for the award from the Patient-Centered Outcomes Research Institute (PCORI), an independent, nonprofit organization authorized by Congress in 2010. It will assess whether healthy lifestyle interventions plus the diabetes drug metformin are more effective than lifestyle interventions alone in reducing weight gain and metabolic problems and improving the mental health of overweight and obese youth with bipolar disorders.

Studies have shown that patients with bipolar disorder are at greater risk than the general population for being overweight and obese, partly because of treatment with Second Generation Antipsychotic (SGA) medications associated with weight gain.

Melissa DelBello, MD, is the principal investigator at UC for the study, which also involves researchers at Cincinnati Children’s Hospital Medical Center and Long Island Jewish Medical Center in New York. DelBello is the Dr. Stanley and Mickey Kaplan Professor and Chair of the Department of Psychiatry and Behavioral Neuroscience at the UC College of Medicine, a professor of psychiatry and pediatrics, a UC Health psychiatrist and director of the Mood Disorders Center at the UC Neuroscience Institute. 

Michael Sorter, MD, a professor of psychiatry and pediatrics at the College of Medicine and director of the Division of Psychiatry at Cincinnati Children’s, leads the efforts at Cincinnati Children’s, and Christoph Correll, MD, a professor of psychiatry and molecular medicine at Hofstra North Shore-Long Island Jewish School of Medicine in New York, leads the efforts at Long Island Jewish Medical Center.  

PCORI’s mission is to fund research that will provide patients, their caregivers and clinicians with the evidence-based information needed to make better informed health care decisions. While traditional medical research is obviously important, PCORI says, "pragmatic” studies are needed to answer pressing clinical questions in the real-world setting where care occurs. 

"The whole basis of PCORI is that it’s patient centered,” says Jenna Nott, MOBILITY’S project director, who came to UC in July and has worked in clinical research for eight years. "A lot of the study design was driven by and developed from feedback that we received from patients and parents of children and adolescents with bipolar spectrum disorders. 

"Pharmacological research has typically been based on a very strict, by-the-book protocol on how each study is done, and usually the patients or participants have no say in the study design. But this study is modified based on feedback we received from our family advisory panel. The family advisory panel includes five children who have been diagnosed with bipolar disorders aged 8-20 and their parents. We run everything by them, they give us feedback and then we make changes based on what they recommend.”

The study team had a kickoff meeting in early October, a two-day event that brought together community members and site staff. "Committees are now meeting on a routine basis,” Nott says. 

"Once we get everything set up, there will be a big push for enrollment, then a steady maintenance phase,” says Nott. "We’ll be looking for a total of about 1,800 volunteers, with a study length for each patient of two years.

"This is a long-term study and it’s a larger sample size than previous studies of this type looking at using metformin to control weight gain in adolescents as a result of being on an SGA.”

In addition to patients and family members, the MOBILITY study team is composed of representatives of national advocacy groups and major third-party payers as well as academic researchers. MOBILITY is partnering with numerous regional and national mental health facilities, including community mental health sites and agencies such as the Depression and Bipolar Support Alliance (DBSA) and NAMI (National Alliance for Mental Illness) Southwest Ohio and the American Academy of Child and Adolescent Psychiatry. 

The study’s "patient-centered” design and outcome measures were determined over months of intensive meetings and research to ensure that they address the questions that patients and families identify as most important to them. For example, surveys conducted with help of DBSA and NAMI identified weight gain as the most troubling side effect of second-generation antipsychotics and the principal reason why many patients do not adhere to these effective mood-stabilizing treatments.

Over 20 clinical sites, many based in community settings rather than academic research centers, will participate in the MOBILITY study. Unlike many traditional clinical trials whose tightly controlled procedures do not necessarily resemble usual treatment practices, MOBILITY will closely simulate typical standard of care conditions by enrolling a broad range of patients and imposing few restrictions on their care.

To accommodate this increased variation, MOBILITY will employ cutting-edge statistical methods to understand how treatment outcomes relate to each other and whether they differ among clinical and demographic subgroups. Co-investigator Jeff Welge, PhD, an associate professor in the UC Department of Psychiatry and Behavioral Neuroscience, will lead a group of biostatisticians and data management experts from UC and Cincinnati Children’s. MOBILITY will also leverage the resources of the Center for Clinical and Translational Science and Training (CCTST), including data collection and management using REDCap, a Web-based software platform.

"There will be a lot of data to come out of this study, and it’s going to be very groundbreaking once it gets published,” Nott says.